DEgenerative ROtator Cuff Disease and Botulinum TOXin

Study Overview
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Brief Summary
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The aim of the study is to assess the effectiveness of botulinum toxin in persistent shoulder pain due to degenerative rotator cuff disease.

Detailed Description
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Epidemiology: degenerative rotator cuff disease ranks first in shoulder disorders and is the main cause of chronic shoulder pain in general practice and in rheumatology clinics. It can be responsible for persistent shoulder pain, functional limitation and greatly contributes to occupational disability. The pathogenesis of rotator cuff disease: involves tendon impingement and intrinsic tendinopathic abnormality (supra-spinatus, infra-spinatus, teres minor and sub-scapularis muscles). They include apoptosis of the tenocytes that is induced by mechanical constraints and by local hypoxia. The consequences are secondary inflammation and matrix alteration. Current therapeutic approach: The first-line recommended treatment for degenerative rotator cuff disease is conservative and includes level 1 and 2 oral analgesics; a short sequence of nonsteroidal anti-inflammatory drugs, if necessary; local injections of corticosteroids; and physiotherapy (low level of evidence). Surgery is a conditional later option. Study hypothesis: Reducing mechanical constraints on the supra-spinatus tendon by botulinum toxin may prevent load-induced apoptosis of the tenocytes and tear progression that is associated with clinical expression, and prevent local hypoxia. Furthermore, the muscle inactivity induced by botulinum toxin is not awaited to provide any clinically relevant functional alteration. Aim of the study: The primary objective of the study is to assess the effectiveness of botulinum toxin in persistent shoulder pain due to degenerative rotator cuff disease at one-month follow-up, using Shoulder Pain And Disability Index (SPADI) as outcome criterion. The secondary objective is to assess the effectiveness of botulinum toxin in persistent shoulder pain due to degenerative rotator cuff disease, at three-month follow-up, using SPADI as outcome criterion and safety, the SPADI sub-scores pain and function at 3 months, global improvement perceived at 1 month and 3 months, drug consumption over the 3 months of follow-up, and treatment acceptability at 1 month and 3 months; as well as the tolerance at 1 week.

Official Title
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DEgenerative ROtator Cuff Disease and Botulinum TOXin: a Randomized Trial

Conditions
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Degenerative Rotator Cuff Disease

Intervention / Treatment
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* Drug: The investigational medicinal product is incobotulinumtoxinA (XEOMIN®).
* Other: PLACEBO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 40 years; pain duration > 1 month; pain intensity ≥ 40/100 on visual analog scale; SPADI ≥ 30/100; medication against pain stable at least 30 days before enrolment; pain with or without weakness during the Jobe manoeuver; ultrasonography within the 30 days, showing tendinopathy of the supra-spinatus, with or without tear; affiliation to health insurance Sécurité Sociale; ability to give consent, complete the weekly notebook (collection of drug treatments taken against pain); availability for the visits planned by the protocol; use of an effective method of contraception in women of childbearing potential, started at least 1 month before and lasting for at least 1 month after receiving study treatment. Negative urine test for women of childbearing age Exclusion Criteria: reduced passive range of motion; antero-posterior instability; tendinous calcification; ultrasonography showing concomitant tear of the infra-spinatus or the subscapularis; corticosteroid injection within the previous 30 days; previous surgery of the shoulder; humeral fracture, inflammatory joint disease and neoplastic disorders; contraindication to XEOMIN® (allergy to XEOMIN® or any other botulinum toxin product); skin infection at the planned injection site; participation in another interventional research involving the human person (RIPH) during the 3 months of follow-up of the DEROTOX Research; participation in another RIPH will be possible beyond these 3 months; concomitant use of aminoglycosides, cyclosporine, aminoquinolines and spectinomycine; patients with a history of aspiration pneumonia and dysphagia; patients on anticoagulant therapy or on therapy that may have an anticoagulant effect; Patients with bleeding disorders; Patients with amyotrophic lateral sclerosis, myasthenia gravis or, Lambert-Eaton syndrome; Patients with other conditions causing peripheral neuromuscular dysfunction; In target muscles that show pronounced weakness or atrophy; Women of childbearing age who have not performed a urine pregnancy test and or who have a positive urine pregnancy test; in case of pregnancy, breastfeeding injection of botulinum toxin in the last 6 months vulnerable people (under legal protection, guardianship or curatorship)

Ages Eligible for Study
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Minimum Age: 41 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1- Botulinum toxin<br>The investigational medicinal product is incobotulinumtoxinA (XEOMIN®). The dosage is: Two milliliters of a mixture comprised of XEOMIN® 100 U and saline solution 0.9% will be once injected in the supra-spinatus muscle using ultrasonography guidance. | Drug: The investigational medicinal product is incobotulinumtoxinA (XEOMIN®).<br>* Two milliliters of a mixture comprised of XEOMIN® 100 U and saline solution 0.9% will be once injected in the supra-spinatus muscle using ultrasonography guidance.<br>|
| Placebo Comparator: 2- PLACEBO<br>The placebo comparator represents a saline solution containing an inactive lyophilisate. The dosage is: Two milliliters of a saline solution containing an inactive lyophilisate will be once injected in the supra-spinatus muscle using ultrasonography guidance. | Other: PLACEBO<br>* Two milliliters of a saline solution containing an inactive lyophilisate will be once injected in the supra-spinatus muscle using ultrasonography guidance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total score of the Shoulder Pain And Disability Index at 1 month. 0 to 100; | Total score of the Shoulder Pain And Disability Index : Scale : 0 to 100, with higher score meaning worst outcome | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sub-scores for pain and disability of the Shoulder Pain And Disability Index at 1 month and 3 months Total score of the Shoulder Pain And Disability Index at 3 months Safety at 1 week, 1 month and 3 months | Sub-scores for pain and disability of the Shoulder Pain And Disability Index : Scale : 0 to 100, with higher score meaning worst outcome | week, 1 month and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Degenerative rotator cuff disease, Botulinum toxin, Clinical trial