Evaluation of safety and efficacy of Urtica dioica cataplasm in the Management of Osgood-Schlatter Disease in Young Athletes: A study protocol for randomized, double-blind, placebo controlled clinical trial

Evaluation of safety and efficacy of Urtica dioica cataplasm in the Management of Osgood-Schlatter Disease in Young Athletes: A study protocol for randomized, double-blind, placebo controlled clinical trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluation of safety and efficacy of Urtica dioica cataplasm in the Management of Osgood-Schlatter Disease in Young Athletes: A study protocol for randomized, double-blind, placebo controlled clinical trial Hana Nasrallah, Sahbi El Mtaoua, Ahmed Loghmari, Amal Bouazzi, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8849646/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Osgood-Schlatter disease (OSD) is a common cause of knee pain in young athletes, often requiring rest and standard care for symptom relief. Urtica dioica , a medicinal plant traditionally used for musculoskeletal conditions, may offer a natural alternative. This study aims to evaluate the clinical efficacy and safety of Urtica dioica cataplasm (UDC) for the management of OSD in comparison to standard care. Methods This is a single-center, phase II, randomized, double-blind, placebo-controlled clinical trial. A total of 180 young athletes diagnosed with OSD will be randomly assigned in a 1:1:1 ratio to receive either UDC, placebo, or standard care consisting of rest and vitamin D supplementation. Participants in the UDC and placebo groups will receive topically applied cataplasms twice weekly for six weeks. Functional outcomes will be assessed using the KOOS-Child questionnaire, encompassing five subscales: pain, symptoms, daily living activities, sports and recreation, and knee-related quality of life. Pain intensity will be measured using the Visual Analogue Scale (VAS). Assessments will be performed at baseline, at 6 weeks (end of intervention), and at 3 months post-treatment to evaluate both short- and mid-term effects. Adverse events will be recorded at each follow-up visit. Discussion This is the first randomized clinical trial to investigate the use of UDC in pediatric OSD management. It is hypothesized that UDC will improve knee function, reduce pain severity, and enhance quality of life in affected individuals. Furthermore, it may shorten the rest period required before returning to sports activities, providing a promising complementary option for young athletes. The outcomes of this study could support the integration of safe, plant-based therapeutics into pediatric musculoskeletal care. Trial Registration The trial is prospectively approved and registered by the Human Research Ethics Committee of the Faculty of Medicine of Sousse, Tunisia [CEFMSo_0061_2025, 28/05/2025] and registered at ClinicalTrials.gov under the identifier NCT07096037 ( https://clinicaltrials.gov/study/NCT07096037 , 30/07/2025). Integrative & Complementary Medicine Urtica dioica cataplasm Osgood-Schlatter disease KOOS-Child Visual Analogue Scale pediatric athletes randomized clinical trial Figures Figure 1 Background Osgood-Schlatter Disease (OSD) is a common musculoskeletal disorder observed predominantly in adolescents and young athletes undergoing rapid growth spurts ( 1 ). It is characterized by inflammation and irritation of the tibial tuberosity resulting from repetitive strain, physical overuse, or previous knee trauma ( 2 ). Clinically, it manifests as localized pain, swelling, and, in some cases, gait disturbances, which may progress to long-term functional impairment ( 3 , 4 ). Epidemiological studies suggest a prevalence rate of 9.8%, with a higher incidence among males (3:1 ratio) ( 5 ). The etiology of OSD remains multifactorial and incompletely understood. It is predominantly linked to the physiological imbalance during adolescence, where accelerated bone growth may surpass the adaptability of surrounding musculature and tendons. This discrepancy contributes to increased mechanical stress on the tibial tubercle, resulting in inflammation and microtrauma ( 6 ). Management strategies typically include rest, NSAIDs, physical therapy, and, rarely, surgical intervention ( 1 , 2 , 7 ). However, these treatments primarily aim to alleviate symptoms and inflammation without promoting tissue healing ( 1 ). Additionally, prolonged NSAID use in pediatric populations may induce adverse effects, including gastrointestinal disturbances and nephrotoxicity ( 8 ). In recent years, interest has surged in the application of natural plant-based therapies for managing inflammatory and musculoskeletal conditions. Phytoconstituents such as flavonoids, polyphenols, and terpenoids have demonstrated significant anti-inflammatory, antioxidant, and analgesic properties ( 9 , 10 ). Their potential to modulate key inflammatory mediators and oxidative stress suggests a promising role in OSD management. Nonetheless, scientific evidence regarding phytotherapy for OSD remains limited, with only a single case report documenting plant extract use in this context ( 11 ). Urtica dioica , commonly known as stinging nettle, is a medicinal plant recognized for its broad pharmacological activity and traditional use in treating joint pain, arthritis, urinary disorders, and skin conditions ( 12 ). It is rich in bioactive compounds including polyphenols, flavonoids, vitamins, and minerals, which contribute to its potent anti-inflammatory and antioxidant effects ( 13 , 14 ). Experimental data supports its ability to downregulate pro-inflammatory cytokines (e.g., TNF-α, IL-1β) and enzymes such as COX-2, while enhancing endogenous antioxidant defenses ( 15 , 16 ). Importantly, U. dioica is associated with a favorable safety profile and low toxicity, making it a suitable candidate for pediatric use ( 17 , 18 ). Objective The primary objective of this clinical trial is to evaluate the efficacy and safety of a topical Urtica dioica cataplasm in managing knee pain and functional limitations in athletic children diagnosed with Osgood-Schlatter Disease. To our knowledge, this is the first randomized trial to explore the therapeutic potential of U. dioica in this indication. Materials and Methods Aim of the study The objective of this clinical trial is to evaluate the efficacy and safety of a topical Urtica dioica cataplasm in managing knee pain and functional limitations in athletic children diagnosed with Osgood-Schlatter Disease. Efficacy will be assessed through changes in knee pain using the Visual Analog Scale (VAS) and functional outcomes using the Knee Injury and Osteoarthritis Outcome Score (KOOS). The results are expected to provide preliminary evidence supporting the integration of phytotherapeutic approaches in pediatric musculoskeletal care. Trial Design This study is designed as a single-center, double-blind, parallel, prospective, randomized controlled clinical trial conducted at the Sports Complex of the Etoile Sportive du Sahel, Sousse, Tunisia. The total duration of the study is 12 weeks, comprising a 6-week intervention period followed by a 6-week post-treatment (washout) phase. Pain severity and functional outcomes will be assessed periodically throughout the study to evaluate both short- and long-term effects of the interventions. Additionally, the trial conduct will be monitored through regular review of data collection and participant compliance to ensure adherence to the study protocol. Any important modifications to the study protocol will be documented and submitted for approval to the relevant ethics committee before implementation. Once approved, these changes will be communicated promptly to all relevant parties, including study investigators, participating sites, and trial participants (when applicable). Written informed consent will be obtained from all participants’ legal guardians prior to enrollment. Participants and Interventions Eligible participants will be identified through collaboration with team physicians and physical trainers at the Sports Complex. Information about the study will be distributed to families of registered youth athletes, and those expressing interest will be screened for eligibility by the study team. A total of 180 male children, aged 7 to 15 years, diagnosed with Osgood-Schlatter Disease (OSD) based on clinical evaluation, will be enrolled and randomly assigned in a 1:1:1 ratio into three parallel groups: UDC Group : topical application of Urtica dioica cataplasm Standard Care Group : oral vitamin D supplementation and physical rest Placebo Group : topical application of a placebo cataplasm using Beta vulgaris subsp. Cicla Random allocation will be concealed using sequentially numbered, opaque, sealed envelopes prepared by an independent third party not involved in participant enrollment or intervention delivery. Blinding will be maintained for participants and outcome assessors throughout the study, except in cases where a medical emergency requires unblinding. Inclusion Criteria Healthy male children between 7 and 15 years of age Active in regular sports practice (e.g., football) Clinically confirmed diagnosis of OSD Exclusion Criteria Known allergy to Urtica dioica Presence of dermatological conditions or lesions on the knees Recent use of anti-inflammatory medications History of immune or chronic inflammatory diseases Diagnosis of any other bone disorder Group Interventions UDC Group : Participants will receive a warm Urtica dioica cataplasm applied topically on the affected knee, once daily for 60 minutes, three times per week (on alternate days) over a 6-week period. Standard Care Group : Participants will receive oral vitamin D (Sterogyl®, 3 drops daily for 1 month) combined with activity reduction as advised by their orthopedic specialist. Placebo Group : Participants will receive a placebo cataplasm prepared using Beta vulgaris subsp. cicla , matched in texture, color, and odor to the active treatment. The placebo is inert and safe for pediatric topical use. Preparation and Application of the Cataplasm Fresh leaves of Urtica dioica will be thoroughly washed, lightly steamed, and crushed. The plant material will then be wrapped in sterile gauze and applied directly to the anterior aspect of the knee. All preparation and application steps will be standardized to ensure consistency across treatment groups and to maintain blinding. Study Procedures Prior to randomization, demographic, nutritional, and medical histories will be collected. Participants will be instructed to avoid the use of any additional anti-inflammatory medications, physiotherapy sessions, herbal remedies, or topical treatments during the study period unless medically necessary. Any use of concomitant care will be recorded and monitored. Participants will be randomized into one of the three intervention groups using a computer-generated sequence. The cataplasm applications will follow a fixed schedule (every other day), and participants will be closely monitored for compliance, clinical progress, and adverse events. In the event of any harm or adverse effects resulting from trial participation, medical care will be provided according to institutional policies. Functional assessment will be performed at baseline and at the end of the 6-week treatment period. The trial flow chart of the study is represented in Fig. 1. No interim analyses or formal stopping rules are planned; however, participants retain the right to withdraw from the study at any point, and investigators may discontinue participation in case of non-compliance or adverse reactions. All interventions, including preparation and application of cataplasms, will be administered by trained clinical personnel (physiotherapists or nurses) under the supervision of a physician experienced in pediatric musculoskeletal care. Personnel involved in outcome assessments will be trained in the use of KOOS-Child and VAS scales to ensure consistency. Personal information about potential and enrolled participants will be handled in accordance with applicable data protection laws and institutional policies. Participant information will be coded to protect identity and accessible only to authorized study personnel. Data sharing outside the study team will occur only in de-identified or aggregate form, ensuring confidentiality before, during, and after the trial. Outcome Measures Primary Outcome Pain intensity : measured using the Visual Analog Scale (VAS), a 10-cm line anchored by “no pain” (0) and “worst imaginable pain” ( 10 ). VAS scores will be recorded at each clinical visit during the intervention period. Secondary Outcomes Functional knee status : assessed using the KOOS-Child questionnaire, covering five subscales (pain, symptoms, activities of daily living, sport/recreation function, and knee-related quality of life). Scores range from 0 (extreme dysfunction) to 100 (no symptoms). Assessments will be done at baseline and after 6 weeks. Return to sport : defined as the number of days post-treatment needed to resume regular athletic activity. Safety Outcomes Adverse events (skin reactions, discomfort, or other clinical complaints) will be recorded systematically at each follow-up visit and assessed by the clinical team. Ethical Considerations This study protocol has been reviewed and approved by the Human Research Ethics Committee of the Faculty of Medicine, University of Sousse, Tunisia [CEFMSo_0061_2025, 28/05/2025]. The study will be conducted in accordance with the principles outlined in the Declaration of Helsinki. Given the minimal risk nature of the intervention, no independent Data Monitoring Committee (DMC) was established. Oversight and safety monitoring will be carried out by the study investigators in coordination with the ethics committee Sample Size and Statistical Analysis Assuming a significance level (α) of 0.05, and 80% power (1 − β), the total sample size required was calculated to be 159 participants. To account for a dropout rate of 10–15%, the final sample size was increased to 180 participants, with 60 participants per group. Data will be analyzed using SPSS software (version 28.0, IBM Corp., NY, USA). Continuous variables will be expressed as mean ± standard deviation. Between-group comparisons will be performed using the independent t-test or Mann–Whitney U test, depending on the data distribution. A p-value of < 0.05 will be considered statistically significant. All data will be recorded on case report forms and subsequently entered into a secure, access-restricted electronic database. Regular data audits will be performed to ensure accuracy and consistency. All analyses will follow the intention-to-treat principle, whereby all randomized participants will be included in the group to which they were assigned, regardless of adherence or protocol deviations. Missing data will be handled according to the last observation. Sensitivity analyses will be conducted to assess the impact of missing data on study outcomes. Study status and timeline This study is currently ongoing. Participant recruitment started in September 2025 and is anticipated to be completed by September 2026. Data collection began concurrently in September 2025 and is scheduled to conclude within one year (by September 2026). No data analysis has been performed to date, and no results have yet been generated. The analysis phase will commence only after the completion of data collection, with study results expected to be then available. Discussion Osgood-Schlatter Disease (OSD) is recognized as a prevalent cause of anterior knee pain among adolescents engaged in physical activities, particularly during periods of rapid skeletal growth. The underlying pathology involves traction-induced microtrauma at the tibial tuberosity, leading to localized inflammation, swelling, and compromised knee function ( 19 , 20 ). Current management strategies for OSD typically include physical rest, targeted physiotherapy, vitamin D supplementation, and non-steroidal anti-inflammatory drugs (NSAIDs) ( 21 , 22 ). While conservative in nature, these approaches are not always effective, and persistent cases may require surgical intervention, generally postponed until skeletal maturity ( 23 ). Moreover, prolonged NSAID use in pediatric populations is associated with undesirable adverse effects, underscoring the necessity for safer, evidence-based alternatives that promote recovery without systemic toxicity ( 24 , 25 ). The functional implications of OSD extend beyond localized pain, often disrupting the athletic participation and competitive trajectory of affected children ( 26 ). Such interruptions, particularly during formative years, may adversely impact not only physical conditioning but also psychological well-being, manifesting as frustration, anxiety, or diminished self-esteem ( 27 , 28 ). These multidimensional challenges highlight the need for therapeutic interventions that ensure effective symptom relief while enabling a safe and timely return to physical activity ( 29 ). Urtica dioica (commonly known as stinging nettle) has been traditionally employed in various ethnomedical systems for the management of inflammatory, rheumatologic, and musculoskeletal disorders ( 30 , 31 ). Its pharmacological potential has been attributed to a complex phytochemical composition that includes polyphenols, flavonoids, carotenoids, sterols, and phenolic acids ( 32 , 33 ). These constituents exert antioxidant, anti-inflammatory, and analgesic effects through the modulation of cytokine expression and oxidative stress pathways ( 34 , 35 ). Several clinical investigations have demonstrated the efficacy of U. dioica in alleviating joint-related pain and improving physical function, particularly in patients with arthritis ( 30 ). A notable study by Randall et al. demonstrated significant symptom reduction in osteoarthritic patients using topically applied fresh nettle leaves, supporting the rationale for its local application ( 36 ). Despite its potential, the stinging sensation induced by direct contact with fresh U. dioica leaves commonly known as the urtication response limits its direct use in certain populations, particularly children. The use of a cataplasm offers a pragmatic alternative, allowing for the controlled application of active compounds directly to the affected site, reducing systemic absorption and minimizing the risk of adverse effects. This localized approach may enhance both safety and efficacy, particularly in pediatric populations. Recent studies have confirmed that cataplasm-based interventions result in low systemic exposure and a reduced incidence of skin irritation ( 37 ). To date, no clinical trials have evaluated the application of U. dioica cataplasm in OSD. This trial represents the first effort to systematically assess its clinical efficacy and safety in comparison to standard care and placebo in children with confirmed OSD. Beta vulgaris subsp. cicla (Swiss chard) was selected as the placebo comparator, due to its absence of topical anti-inflammatory or analgesic properties in current scientific literature and its physical similarity to U. dioica , thereby supporting effective blinding. In this study, outcome measures were chosen to reflect both subjective and objective dimensions of patient recovery. The KOOS-Child questionnaire, specifically validated for pediatric musculoskeletal conditions, assesses pain, function, and quality of life through five subscales, providing a comprehensive evaluation of clinical outcomes ( 38 ). In parallel, the Visual Analog Scale (VAS) remains a widely accepted instrument for quantifying pain perception in children and adolescents ( 39 ). This investigation aims to generate evidence on the potential of Urtica dioica cataplasm as a plant-based, well-tolerated, and non-invasive therapeutic option for managing OSD. By reducing pain and improving function, this intervention could support early reintegration into sports activities, mitigate the psychological burden associated with prolonged athletic withdrawal, and ultimately promote better musculoskeletal health during critical phases of development. The outcomes of this trial may provide important insights into the integration of phytotherapy within pediatric orthopedic care. Abbreviations OSD Osgood-Schlatter disease UDC Urtica dioica cataplasm KOOS Knee injury and Osteoarthritis Outcome Score VAS Visual Analogue Scale NSAIDs Non-steroidal anti-inflammatory drugs Declarations Ethics approval and consent to participate The trial was approved by the Human Research Ethics Committee of the Faculty of Medicine of Sousse, Tunisia [CEFMSo_0061_2025, 28/05/2025]. Written informed consent will be obtained from all participants’ legal guardians prior to enrollment. Availability of data and materials The datasets used during the current study are available from the corresponding author on reasonable request. Results will be published in peer-reviewed journals and shared with participants upon request. Funding None. Competing interests The authors declare that they have no competing interests. Authors' contributions H.N. contributed to the development of the clinical protocol, preparation of the Urtica dioica cataplasm, and drafting of the manuscript. N.E.F. participated in patient recruitment, clinical assessment, and data collection. A.L. contributed to the methodological design, randomization procedure, and statistical planning. M.G. assisted in clinical monitoring, follow-up assessments, and data management. R.M. contributed to laboratory analyses and quality control of the plant preparation. A.B. participated in participant evaluation, safety monitoring, and adverse-event reporting. S.E.M. contributed to the study conceptualization, data interpretation and critical revision of the manuscript for important intellectual content. A.Z. contributed to the study conceptualization, supervised the overall project, ensured regulatory and ethical compliance, and provided final approval of the manuscript. All authors read and approved the final manuscript. Acknowledgements The Faculty of Medicine of Sousse, Tunisia supported the development of the study design, facilitated ethical approval, and will oversee implementation, monitoring, data management, statistical analysis, and publication of the findings. Faculty of Medicine of Sousse, University of Sousse, Avenue Ibn El Jazzar, 4002 Sousse, Tunisia Tel: +21673 222 108 Consent for publication Not applicable. References Neuhaus C, Appenzeller-Herzog C, Faude O (2021) A systematic review on conservative treatment options for OSGOOD-Schlatter disease. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8849646","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":589504518,"identity":"6984e97f-7f6c-43ed-877c-cbf34ab0459f","order_by":0,"name":"Hana Nasrallah","email":"","orcid":"https://orcid.org/0000-0001-9361-2417","institution":"Department of Biochemistry, Faculty of Medicine of Sousse, University of Sousse, 4002, Sousse, Tunisia","correspondingAuthor":false,"prefix":"","firstName":"Hana","middleName":"","lastName":"Nasrallah","suffix":""},{"id":589504519,"identity":"1f3922b2-2d9f-4fb3-b937-43aa148403ef","order_by":1,"name":"Sahbi El Mtaoua","email":"","orcid":"","institution":"Department of Physical Medicine and Rehabilitation, Hospital Ibn Jazzar of Kairouan, University of Sousse, 4002, Sousse, Tunisia","correspondingAuthor":false,"prefix":"","firstName":"Sahbi","middleName":"El","lastName":"Mtaoua","suffix":""},{"id":589504520,"identity":"345853ca-ccc6-415b-8f47-5ab956b2d35b","order_by":2,"name":"Ahmed Loghmari","email":"","orcid":"","institution":"Urology Department, Sahloul Hospital, University of Sousse, Sousse 4054, Tunisia","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"","lastName":"Loghmari","suffix":""},{"id":589504521,"identity":"6ad24982-da44-4d39-a9dd-42ac977f2ea3","order_by":3,"name":"Amal Bouazzi","email":"","orcid":"","institution":"Department of General Surgery, Sahloul University Hospital, Medicine Faculty of Sousse, University of Sousse, Sousse 4002, Tunisia","correspondingAuthor":false,"prefix":"","firstName":"Amal","middleName":"","lastName":"Bouazzi","suffix":""},{"id":589504522,"identity":"4c7c06fe-0f16-4839-912f-63e8e9744bf9","order_by":4,"name":"Amira Zairi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYFACxgaGBCDFBmQ9YGA4wAChidTCbADRAqKJBGwSRGmRbz/c9uEBg100n/ThZ9U8NXfk+BmY2T7gdVZPYvOMBIbk3Da+NLPbPMeeGUs2MDPPwKeFmSGxGegX5tw2HgagFrbDiRsO8B/G737+hyAt9UAt7N+Kef6BtDAz49XCIwG25TBQC48ZM28bEVokJMC2HAdpKZac23fYWLKZgBb5/vTHjD8YqnPn97Bv/PDm22E5fvZm/FrAgPEfhGbiAZFEaEDS+oMU1aNgFIyCUTBiAAAp/UEfa5IaCAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-6662-0689","institution":"Department of Biochemistry, Faculty of Medicine of Sousse, University of Sousse, 4002, Sousse, Tunisia","correspondingAuthor":true,"prefix":"","firstName":"Amira","middleName":"","lastName":"Zairi","suffix":""}],"badges":[],"createdAt":"2026-02-11 09:23:02","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":true,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-8849646/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8849646/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102491235,"identity":"666a855a-1c29-4948-9433-8fcc4592709d","added_by":"auto","created_at":"2026-02-12 08:42:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":159918,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the study\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-8849646/v1/671f6259486411a3d457c49a.png"},{"id":102491419,"identity":"bad35d13-ffaf-456e-b697-1e63eabb8f30","added_by":"auto","created_at":"2026-02-12 08:43:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":879071,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8849646/v1/8a3988a9-e862-4c74-85b7-0de8ecbf5fbd.pdf"},{"id":102491183,"identity":"087f1abd-0026-4524-9135-b6752601efde","added_by":"auto","created_at":"2026-02-12 08:42:41","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":41314,"visible":true,"origin":"","legend":"","description":"","filename":"SPIRIT2025.docx","url":"https://assets-eu.researchsquare.com/files/rs-8849646/v1/fe358530084d2d0f2f77af1e.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eEvaluation of safety and efficacy of \u003cem\u003eUrtica dioica\u003c/em\u003e cataplasm in the Management of Osgood-Schlatter Disease in Young Athletes: A study protocol for randomized, double-blind, placebo controlled clinical trial\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eOsgood-Schlatter Disease (OSD) is a common musculoskeletal disorder observed predominantly in adolescents and young athletes undergoing rapid growth spurts (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It is characterized by inflammation and irritation of the tibial tuberosity resulting from repetitive strain, physical overuse, or previous knee trauma (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Clinically, it manifests as localized pain, swelling, and, in some cases, gait disturbances, which may progress to long-term functional impairment (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Epidemiological studies suggest a prevalence rate of 9.8%, with a higher incidence among males (3:1 ratio) (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe etiology of OSD remains multifactorial and incompletely understood. It is predominantly linked to the physiological imbalance during adolescence, where accelerated bone growth may surpass the adaptability of surrounding musculature and tendons. This discrepancy contributes to increased mechanical stress on the tibial tubercle, resulting in inflammation and microtrauma (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Management strategies typically include rest, NSAIDs, physical therapy, and, rarely, surgical intervention (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). However, these treatments primarily aim to alleviate symptoms and inflammation without promoting tissue healing (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Additionally, prolonged NSAID use in pediatric populations may induce adverse effects, including gastrointestinal disturbances and nephrotoxicity (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn recent years, interest has surged in the application of natural plant-based therapies for managing inflammatory and musculoskeletal conditions. Phytoconstituents such as flavonoids, polyphenols, and terpenoids have demonstrated significant anti-inflammatory, antioxidant, and analgesic properties (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Their potential to modulate key inflammatory mediators and oxidative stress suggests a promising role in OSD management. Nonetheless, scientific evidence regarding phytotherapy for OSD remains limited, with only a single case report documenting plant extract use in this context (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cem\u003eUrtica dioica\u003c/em\u003e, commonly known as stinging nettle, is a medicinal plant recognized for its broad pharmacological activity and traditional use in treating joint pain, arthritis, urinary disorders, and skin conditions (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). It is rich in bioactive compounds including polyphenols, flavonoids, vitamins, and minerals, which contribute to its potent anti-inflammatory and antioxidant effects (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Experimental data supports its ability to downregulate pro-inflammatory cytokines (e.g., TNF-α, IL-1β) and enzymes such as COX-2, while enhancing endogenous antioxidant defenses (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Importantly, U. dioica is associated with a favorable safety profile and low toxicity, making it a suitable candidate for pediatric use (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eObjective\u003c/h3\u003e\n\u003cp\u003eThe primary objective of this clinical trial is to evaluate the efficacy and safety of a topical \u003cem\u003eUrtica dioica\u003c/em\u003e cataplasm in managing knee pain and functional limitations in athletic children diagnosed with Osgood-Schlatter Disease. To our knowledge, this is the first randomized trial to explore the therapeutic potential of \u003cem\u003eU. dioica\u003c/em\u003e in this indication.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eAim of the study\u003c/h2\u003e \u003cp\u003eThe objective of this clinical trial is to evaluate the efficacy and safety of a topical \u003cem\u003eUrtica dioica\u003c/em\u003e cataplasm in managing knee pain and functional limitations in athletic children diagnosed with Osgood-Schlatter Disease. Efficacy will be assessed through changes in knee pain using the Visual Analog Scale (VAS) and functional outcomes using the Knee Injury and Osteoarthritis Outcome Score (KOOS). The results are expected to provide preliminary evidence supporting the integration of phytotherapeutic approaches in pediatric musculoskeletal care.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTrial Design\u003c/h3\u003e\n\u003cp\u003eThis study is designed as a single-center, double-blind, parallel, prospective, randomized controlled clinical trial conducted at the Sports Complex of the Etoile Sportive du Sahel, Sousse, Tunisia. The total duration of the study is 12 weeks, comprising a 6-week intervention period followed by a 6-week post-treatment (washout) phase. Pain severity and functional outcomes will be assessed periodically throughout the study to evaluate both short- and long-term effects of the interventions. Additionally, the trial conduct will be monitored through regular review of data collection and participant compliance to ensure adherence to the study protocol. Any important modifications to the study protocol will be documented and submitted for approval to the relevant ethics committee before implementation. Once approved, these changes will be communicated promptly to all relevant parties, including study investigators, participating sites, and trial participants (when applicable). Written informed consent will be obtained from all participants\u0026rsquo; legal guardians prior to enrollment.\u003c/p\u003e\n\u003ch3\u003eParticipants and Interventions\u003c/h3\u003e\n\u003cp\u003eEligible participants will be identified through collaboration with team physicians and physical trainers at the Sports Complex. Information about the study will be distributed to families of registered youth athletes, and those expressing interest will be screened for eligibility by the study team.\u003c/p\u003e \u003cp\u003eA total of 180 male children, aged 7 to 15 years, diagnosed with Osgood-Schlatter Disease (OSD) based on clinical evaluation, will be enrolled and randomly assigned in a 1:1:1 ratio into three parallel groups:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eUDC Group\u003c/b\u003e: topical application of \u003cem\u003eUrtica dioica\u003c/em\u003e cataplasm\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eStandard Care Group\u003c/b\u003e: oral vitamin D supplementation and physical rest\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003ePlacebo Group\u003c/b\u003e: topical application of a placebo cataplasm using \u003cem\u003eBeta vulgaris subsp. Cicla\u003c/em\u003e\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eRandom allocation will be concealed using sequentially numbered, opaque, sealed envelopes prepared by an independent third party not involved in participant enrollment or intervention delivery. Blinding will be maintained for participants and outcome assessors throughout the study, except in cases where a medical emergency requires unblinding.\u003c/p\u003e\n\u003ch3\u003eInclusion Criteria\u003c/h3\u003e\n\u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eHealthy male children between 7 and 15 years of age\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eActive in regular sports practice (e.g., football)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eClinically confirmed diagnosis of OSD\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eExclusion Criteria\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eKnown allergy to \u003cem\u003eUrtica dioica\u003c/em\u003e\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePresence of dermatological conditions or lesions on the knees\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eRecent use of anti-inflammatory medications\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eHistory of immune or chronic inflammatory diseases\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eDiagnosis of any other bone disorder\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eGroup Interventions\u003c/h3\u003e\n\u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eUDC Group\u003c/b\u003e: Participants will receive a warm \u003cem\u003eUrtica dioica\u003c/em\u003e cataplasm applied topically on the affected knee, once daily for 60 minutes, three times per week (on alternate days) over a 6-week period.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eStandard Care Group\u003c/b\u003e: Participants will receive oral vitamin D (Sterogyl\u0026reg;, 3 drops daily for 1 month) combined with activity reduction as advised by their orthopedic specialist.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003ePlacebo Group\u003c/b\u003e: Participants will receive a placebo cataplasm prepared using \u003cem\u003eBeta vulgaris subsp. cicla\u003c/em\u003e, matched in texture, color, and odor to the active treatment. The placebo is inert and safe for pediatric topical use.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e\n\u003ch3\u003ePreparation and Application of the Cataplasm\u003c/h3\u003e\n\u003cp\u003eFresh leaves of \u003cem\u003eUrtica dioica\u003c/em\u003e will be thoroughly washed, lightly steamed, and crushed. The plant material will then be wrapped in sterile gauze and applied directly to the anterior aspect of the knee. All preparation and application steps will be standardized to ensure consistency across treatment groups and to maintain blinding.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStudy Procedures\u003c/h2\u003e \u003cp\u003ePrior to randomization, demographic, nutritional, and medical histories will be collected. Participants will be instructed to avoid the use of any additional anti-inflammatory medications, physiotherapy sessions, herbal remedies, or topical treatments during the study period unless medically necessary. Any use of concomitant care will be recorded and monitored.\u003c/p\u003e \u003cp\u003eParticipants will be randomized into one of the three intervention groups using a computer-generated sequence. The cataplasm applications will follow a fixed schedule (every other day), and participants will be closely monitored for compliance, clinical progress, and adverse events. In the event of any harm or adverse effects resulting from trial participation, medical care will be provided according to institutional policies. Functional assessment will be performed at baseline and at the end of the 6-week treatment period. The trial flow chart of the study is represented in Fig.\u0026nbsp;1. No interim analyses or formal stopping rules are planned; however, participants retain the right to withdraw from the study at any point, and investigators may discontinue participation in case of non-compliance or adverse reactions.\u003c/p\u003e \u003cp\u003eAll interventions, including preparation and application of cataplasms, will be administered by trained clinical personnel (physiotherapists or nurses) under the supervision of a physician experienced in pediatric musculoskeletal care. Personnel involved in outcome assessments will be trained in the use of KOOS-Child and VAS scales to ensure consistency.\u003c/p\u003e \u003cp\u003ePersonal information about potential and enrolled participants will be handled in accordance with applicable data protection laws and institutional policies. Participant information will be coded to protect identity and accessible only to authorized study personnel. Data sharing outside the study team will occur only in de-identified or aggregate form, ensuring confidentiality before, during, and after the trial.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eOutcome Measures\u003c/h2\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003ch2\u003ePrimary Outcome\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003ePain intensity\u003c/b\u003e: measured using the Visual Analog Scale (VAS), a 10-cm line anchored by \u0026ldquo;no pain\u0026rdquo; (0) and \u0026ldquo;worst imaginable pain\u0026rdquo; (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). VAS scores will be recorded at each clinical visit during the intervention period.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eSecondary Outcomes\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eFunctional knee status\u003c/b\u003e: assessed using the KOOS-Child questionnaire, covering five subscales (pain, symptoms, activities of daily living, sport/recreation function, and knee-related quality of life). Scores range from 0 (extreme dysfunction) to 100 (no symptoms). Assessments will be done at baseline and after 6 weeks.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eReturn to sport\u003c/b\u003e: defined as the number of days post-treatment needed to resume regular athletic activity.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eSafety Outcomes\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eAdverse events (skin reactions, discomfort, or other clinical complaints) will be recorded systematically at each follow-up visit and assessed by the clinical team.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eEthical Considerations\u003c/h2\u003e \u003cp\u003eThis study protocol has been reviewed and approved by the Human Research Ethics Committee of the Faculty of Medicine, University of Sousse, Tunisia [CEFMSo_0061_2025, 28/05/2025]. The study will be conducted in accordance with the principles outlined in the Declaration of Helsinki. Given the minimal risk nature of the intervention, no independent Data Monitoring Committee (DMC) was established. Oversight and safety monitoring will be carried out by the study investigators in coordination with the ethics committee\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eSample Size and Statistical Analysis\u003c/h2\u003e \u003cp\u003eAssuming a significance level (α) of 0.05, and 80% power (1\u0026thinsp;\u0026minus;\u0026thinsp;β), the total sample size required was calculated to be 159 participants. To account for a dropout rate of 10\u0026ndash;15%, the final sample size was increased to 180 participants, with 60 participants per group.\u003c/p\u003e \u003cp\u003eData will be analyzed using SPSS software (version 28.0, IBM Corp., NY, USA). Continuous variables will be expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Between-group comparisons will be performed using the independent t-test or Mann\u0026ndash;Whitney U test, depending on the data distribution. A p-value of \u0026lt;\u0026thinsp;0.05 will be considered statistically significant.\u003c/p\u003e \u003cp\u003eAll data will be recorded on case report forms and subsequently entered into a secure, access-restricted electronic database. Regular data audits will be performed to ensure accuracy and consistency.\u003c/p\u003e \u003cp\u003eAll analyses will follow the intention-to-treat principle, whereby all randomized participants will be included in the group to which they were assigned, regardless of adherence or protocol deviations. Missing data will be handled according to the last observation. Sensitivity analyses will be conducted to assess the impact of missing data on study outcomes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eStudy status and timeline\u003c/h2\u003e \u003cp\u003eThis study is currently ongoing. Participant recruitment started in September 2025 and is anticipated to be completed by September 2026. Data collection began concurrently in September 2025 and is scheduled to conclude within one year (by September 2026). No data analysis has been performed to date, and no results have yet been generated. The analysis phase will commence only after the completion of data collection, with study results expected to be then available.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOsgood-Schlatter Disease (OSD) is recognized as a prevalent cause of anterior knee pain among adolescents engaged in physical activities, particularly during periods of rapid skeletal growth. The underlying pathology involves traction-induced microtrauma at the tibial tuberosity, leading to localized inflammation, swelling, and compromised knee function (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Current management strategies for OSD typically include physical rest, targeted physiotherapy, vitamin D supplementation, and non-steroidal anti-inflammatory drugs (NSAIDs) (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). While conservative in nature, these approaches are not always effective, and persistent cases may require surgical intervention, generally postponed until skeletal maturity (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Moreover, prolonged NSAID use in pediatric populations is associated with undesirable adverse effects, underscoring the necessity for safer, evidence-based alternatives that promote recovery without systemic toxicity (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe functional implications of OSD extend beyond localized pain, often disrupting the athletic participation and competitive trajectory of affected children (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Such interruptions, particularly during formative years, may adversely impact not only physical conditioning but also psychological well-being, manifesting as frustration, anxiety, or diminished self-esteem (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). These multidimensional challenges highlight the need for therapeutic interventions that ensure effective symptom relief while enabling a safe and timely return to physical activity (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cem\u003eUrtica dioica\u003c/em\u003e (commonly known as stinging nettle) has been traditionally employed in various ethnomedical systems for the management of inflammatory, rheumatologic, and musculoskeletal disorders (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Its pharmacological potential has been attributed to a complex phytochemical composition that includes polyphenols, flavonoids, carotenoids, sterols, and phenolic acids (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). These constituents exert antioxidant, anti-inflammatory, and analgesic effects through the modulation of cytokine expression and oxidative stress pathways (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Several clinical investigations have demonstrated the efficacy of \u003cem\u003eU. dioica\u003c/em\u003e in alleviating joint-related pain and improving physical function, particularly in patients with arthritis (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). A notable study by Randall et al. demonstrated significant symptom reduction in osteoarthritic patients using topically applied fresh nettle leaves, supporting the rationale for its local application (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite its potential, the stinging sensation induced by direct contact with fresh \u003cem\u003eU. dioica\u003c/em\u003e leaves commonly known as the urtication response limits its direct use in certain populations, particularly children. The use of a cataplasm offers a pragmatic alternative, allowing for the controlled application of active compounds directly to the affected site, reducing systemic absorption and minimizing the risk of adverse effects. This localized approach may enhance both safety and efficacy, particularly in pediatric populations. Recent studies have confirmed that cataplasm-based interventions result in low systemic exposure and a reduced incidence of skin irritation (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTo date, no clinical trials have evaluated the application of \u003cem\u003eU. dioica\u003c/em\u003e cataplasm in OSD. This trial represents the first effort to systematically assess its clinical efficacy and safety in comparison to standard care and placebo in children with confirmed OSD. \u003cem\u003eBeta vulgaris subsp. cicla\u003c/em\u003e (Swiss chard) was selected as the placebo comparator, due to its absence of topical anti-inflammatory or analgesic properties in current scientific literature and its physical similarity to \u003cem\u003eU. dioica\u003c/em\u003e, thereby supporting effective blinding.\u003c/p\u003e \u003cp\u003eIn this study, outcome measures were chosen to reflect both subjective and objective dimensions of patient recovery. The KOOS-Child questionnaire, specifically validated for pediatric musculoskeletal conditions, assesses pain, function, and quality of life through five subscales, providing a comprehensive evaluation of clinical outcomes (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). In parallel, the Visual Analog Scale (VAS) remains a widely accepted instrument for quantifying pain perception in children and adolescents (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis investigation aims to generate evidence on the potential of \u003cem\u003eUrtica dioica\u003c/em\u003e cataplasm as a plant-based, well-tolerated, and non-invasive therapeutic option for managing OSD. By reducing pain and improving function, this intervention could support early reintegration into sports activities, mitigate the psychological burden associated with prolonged athletic withdrawal, and ultimately promote better musculoskeletal health during critical phases of development. The outcomes of this trial may provide important insights into the integration of phytotherapy within pediatric orthopedic care.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOsgood-Schlatter disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUDC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e \u003cem\u003eUrtica dioica\u003c/em\u003e cataplasm\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKOOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKnee injury and Osteoarthritis Outcome Score\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVAS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVisual Analogue Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNSAIDs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNon-steroidal anti-inflammatory drugs\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial was approved by the Human Research Ethics Committee of the Faculty of Medicine of Sousse, Tunisia [CEFMSo_0061_2025, 28/05/2025]. Written informed consent will be obtained from all participants\u0026rsquo; legal guardians prior to enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used during the current study are available from the corresponding author on reasonable request. Results will be published in peer-reviewed journals and shared with participants upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eH.N.\u003c/strong\u003e contributed to the development of the clinical protocol, preparation of the Urtica dioica cataplasm, and drafting of the manuscript. \u003cstrong\u003eN.E.F.\u003c/strong\u003e participated in patient recruitment, clinical assessment, and data collection. \u003cstrong\u003eA.L.\u003c/strong\u003e contributed to the methodological design, randomization procedure, and statistical planning. \u003cstrong\u003eM.G.\u003c/strong\u003e assisted in clinical monitoring, follow-up assessments, and data management. \u003cstrong\u003eR.M.\u003c/strong\u003e contributed to laboratory analyses and quality control of the plant preparation. \u003cstrong\u003eA.B.\u003c/strong\u003e participated in participant evaluation, safety monitoring, and adverse-event reporting. \u003cstrong\u003eS.E.M.\u003c/strong\u003e contributed to the study conceptualization, data interpretation and critical revision of the manuscript for important intellectual content. \u003cstrong\u003eA.Z.\u003c/strong\u003e contributed to the study conceptualization, supervised the overall project, ensured regulatory and ethical compliance, and provided final approval of the manuscript.\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Faculty of Medicine of Sousse, Tunisia supported the development of the study design, facilitated ethical approval, and will oversee implementation, monitoring, data management, statistical analysis, and publication of the findings.\u003c/p\u003e\n\u003cp\u003eFaculty of Medicine of Sousse,\u003c/p\u003e\n\u003cp\u003eUniversity of Sousse,\u003c/p\u003e\n\u003cp\u003eAvenue Ibn El Jazzar, 4002 Sousse, Tunisia\u003c/p\u003e\n\u003cp\u003eTel: +21673 222 108\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eNeuhaus C, Appenzeller-Herzog C, Faude O (2021) A systematic review on conservative treatment options for OSGOOD-Schlatter disease. 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J Ayurvedic Herb Med 3(4):189\u0026ndash;191\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrauso L, De Falco B, Lanzotti V, Motti R (2020) Stinging nettle, Urtica dioica L.: Botanical, phytochemical and pharmacological overview. Phytochem Rev 19:1341\u0026ndash;1377\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\\DJurović S, Kojić I, Radić D, Smyatskaya YA, Bazarnova JG, Filip S et al (2024) Chemical constituents of stinging nettle (Urtica dioica L.): A comprehensive review on phenolic and polyphenolic compounds and their bioactivity. Int J Mol Sci 25(6):3430\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJan KN, Zarafshan K, Singh S (2017) Stinging nettle (Urtica dioica L.): a reservoir of nutrition and bioactive components with great functional potential. 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MRMC. 6 d\u0026eacute;c ;19(1):63\u0026ndash;71\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaheri Y, Quispe C, Herrera-Bravo J, Sharifi-Rad J, Ezzat SM, Merghany RM et al (2022) Urtica dioica-Derived Phytochemicals for Pharmacological and Therapeutic Applications. Mota Da Silva LS, \u0026eacute;diteur. Evidence-Based Complement Altern Med 24 f\u0026eacute;vr 2022:1\u0026ndash;30\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaya DO, Toprak U, Baltaci G, Yosmaoglu B, Ozer H (2013) Long-term functional and sonographic outcomes in Osgood\u0026ndash;Schlatter disease. Knee surg sports traumatol arthrosc mai 21(5):1131\u0026ndash;1139\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRathleff MS, Winiarski L, Krommes K, Graven-Nielsen T, H\u0026ouml;lmich P, Olesen JL et al (2020) Activity Modification and Knee Strengthening for Osgood-Schlatter Disease: A Prospective Cohort Study. Orthop J Sports Med 1 avr 8(4):2325967120911106\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGraff CJ, Barber K, Meron A (2022) Update on Management of Leg Pain in Athletes. Curr Phys Med Rehabil Rep 25 mai 10(3):216\u0026ndash;224\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKidd PS, McCoy C, Steenbergen L (2000) Repetitive strain injuries in youth. J Am Association Nurse Practitioners 12(10):413\u0026ndash;426\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCirci E, Atalay Y, Beyzadeoglu T (2017) Treatment of Osgood\u0026ndash;Schlatter disease: review of the literature. Musculoskelet Surg d\u0026eacute;c 101(3):195\u0026ndash;200\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePreuss FR, Whalen RJ, Buchalter WH, Ganokroj P, Provencher BT, Provencher MT (2024) Osgood-Schlatter Disease: Ossicle Resection and Patellar Tendon Repair in a Symptomatic Adult. Arthrosc Techniques 13(11):103110\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSinggih MF, Achmad H, Sukmana BI, Carmelita AB, Putra AP, Ramadhany S et al (2020) A review of nonsteroidal anti-inflammatory drugs (NSAIDs) medications in dentistry: uses and side effects. Syst Reviews Pharm 11(5):293\u0026ndash;298\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBruzda R, Wilczyński B, Zorena K (2023) Knee function and quality of life in adolescent soccer players with Osgood Shlatter disease history: a preliminary study. Sci Rep 13(1):19200\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHOLDEN, Sinead OLESEN, Jens Lykkegaard WINIARSKI, Lukasz M et al (2021) Is the prognosis of Osgood-Schlatter poorer than anticipated? A prospective cohort study with 24-month follow-up. Orthop J sports Med 9:23259671211022239\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRathleff MS, Winiarski L, Krommes K, Graven-Nielsen T, H\u0026ouml;lmich P, Olesen JL et al (2020) Pain, Sports Participation, and Physical Function in Adolescents With Patellofemoral Pain and Osgood-Schlatter Disease: A Matched Cross-sectional Study. J Orthop Sports Phys Therapy mars 50(3):149\u0026ndash;157\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVarghese M, Ruparell S, LaBella C (2022) Youth Athlete Development Models: A Narrative Review. Sports Health: Multidisciplinary Approach janv 14(1):20\u0026ndash;29\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRathaur H, Juyal D, Mukhopadhyay S, ARTHRITIS ALLEVIATION WITH URTICA, DIOICA: UNVEILING THE LATEST FINDINGS FROM PRECLINICAL AND CLINICAL TRIALS. Biochem Cell Archives, 24(1)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZawawi SSA, Zamli Z, SAAD N (2023) The effectiveness and application of Urtica dioica (stinging nettle) for musculoskeletal disorders: a systematic review and meta-analysis. Int J Allied Health Sci 7(1):2863\u0026ndash;2874\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDevkota HP, Paudel KR, Khanal S, Baral A, Panth N, Adhikari-Devkota A et al (2022) Stinging nettle (Urtica dioica L.): Nutritional composition, bioactive compounds, and food functional properties. Molecules 27(16):5219\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJafari Z, Samani SA, Jafari M (2020) Insights into the bioactive compounds and physico-chemical characteristics of the extracted oils from Urtica dioica and Urtica pilulifera. SN Appl Sci mars 2(3):416\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsgarpanah J, Mohajerani R (2012) Phytochemistry and pharmacologic properties of Urtica dioica L. J Med plants Res 6(46):5714\u0026ndash;5719\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eG\u0026uuml;l\u0026ccedil;in I, K\u0026uuml;frevioǧlu \u0026Ouml;İ, Oktay M, B\u0026uuml;y\u0026uuml;kokuroǧlu ME (2004) Antioxidant, antimicrobial, antiulcer and analgesic activities of nettle (Urtica dioica L). J Ethnopharmacol 90(2\u0026ndash;3):205\u0026ndash;215\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRandall C, Randall H, Dobbs F, Hutton C, Sanders H (2000) Randomized controlled trial of nettle sting for treatment of base-of-thumb pain. J R Soc Med juin 93(6):305\u0026ndash;309\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi D, Cheng Y, Yuan P, Wu Z, Liu J, Kan J et al (sept 2023) Efficacy and safety of flurbiprofen cataplasms versus loxoprofen sodium cataplasms in knee osteoarthritis: a randomized controlled trial. Chin Med J 20(18):2187\u0026ndash;2194\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026Ouml;rtqvist M, Roos EM, Brostr\u0026ouml;m EW, Janarv PM, Iversen MD (2012) Development of the Knee Injury and Osteoarthritis Outcome Score for Children (KOOS-Child): Comprehensibility and content validity. Acta Orthop d\u0026eacute;c 83(6):666\u0026ndash;673\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVon Baeyer CL, Spagrud LJ (2007) Systematic review of observational (behavioral) measures of pain for children and adolescents aged 3 to 18 years. Pain 127(1\u0026ndash;2):140\u0026ndash;150\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Urtica dioica, cataplasm, Osgood-Schlatter disease, KOOS-Child, Visual Analogue Scale, pediatric athletes, randomized clinical trial","lastPublishedDoi":"10.21203/rs.3.rs-8849646/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8849646/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOsgood-Schlatter disease (OSD) is a common cause of knee pain in young athletes, often requiring rest and standard care for symptom relief. \u003cem\u003eUrtica dioica\u003c/em\u003e, a medicinal plant traditionally used for musculoskeletal conditions, may offer a natural alternative. This study aims to evaluate the clinical efficacy and safety of \u003cem\u003eUrtica dioica\u003c/em\u003e cataplasm (UDC) for the management of OSD in comparison to standard care.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis is a single-center, phase II, randomized, double-blind, placebo-controlled clinical trial. A total of 180 young athletes diagnosed with OSD will be randomly assigned in a 1:1:1 ratio to receive either UDC, placebo, or standard care consisting of rest and vitamin D supplementation. Participants in the UDC and placebo groups will receive topically applied cataplasms twice weekly for six weeks. Functional outcomes will be assessed using the KOOS-Child questionnaire, encompassing five subscales: pain, symptoms, daily living activities, sports and recreation, and knee-related quality of life. Pain intensity will be measured using the Visual Analogue Scale (VAS). Assessments will be performed at baseline, at 6 weeks (end of intervention), and at 3 months post-treatment to evaluate both short- and mid-term effects. Adverse events will be recorded at each follow-up visit.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e \u003cp\u003eThis is the first randomized clinical trial to investigate the use of UDC in pediatric OSD management. It is hypothesized that UDC will improve knee function, reduce pain severity, and enhance quality of life in affected individuals. Furthermore, it may shorten the rest period required before returning to sports activities, providing a promising complementary option for young athletes. The outcomes of this study could support the integration of safe, plant-based therapeutics into pediatric musculoskeletal care.\u003c/p\u003e\u003ch2\u003eTrial Registration\u003c/h2\u003e \u003cp\u003eThe trial is prospectively approved and registered by the Human Research Ethics Committee of the Faculty of Medicine of Sousse, Tunisia [CEFMSo_0061_2025, 28/05/2025] and registered at ClinicalTrials.gov under the identifier NCT07096037 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://clinicaltrials.gov/study/NCT07096037\u003c/span\u003e\u003cspan address=\"https://clinicaltrials.gov/study/NCT07096037\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e, 30/07/2025).\u003c/p\u003e","manuscriptTitle":"Evaluation of safety and efficacy of Urtica dioica cataplasm in the Management of Osgood-Schlatter Disease in Young Athletes: A study protocol for randomized, double-blind, placebo controlled clinical trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-12 08:41:25","doi":"10.21203/rs.3.rs-8849646/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1f330e5e-7586-47e4-8272-e334268879ee","owner":[],"postedDate":"February 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":62720289,"name":"Integrative \u0026 Complementary Medicine"}],"tags":[],"updatedAt":"2026-02-12T08:41:25+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-12 08:41:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8849646","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8849646","identity":"rs-8849646","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}