DEgenerative ROtator Cuff Disease and Botulinum TOXin

Official title

DEgenerative ROtator Cuff Disease and Botulinum TOXin: a Randomized Trial

Overview

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

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.

Interventions

• Drug The investigational medicinal product is incobotulinumtoxinA (XEOMIN®).
  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.
• Other PLACEBO
  Two milliliters of a saline solution containing an inactive lyophilisate will be once injected in the supra-spinatus muscle using ultrasonography guidance.

Primary outcome measures

• Total score of the Shoulder Pain And Disability Index at 1 month. 0 to 100; [Time frame: 1 month]

Secondary outcome measures (1)

• 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 [Time frame: week, 1 month and 3 months]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

France · 1 center

• Hôpital LARIBOISIERE — Paris

Publications

• Badley EM, Tennant A. Changing profile of joint disorders with age: findings from a postal survey of the population of Calderdale, West Yorkshire, United Kingdom. Ann Rheum Dis. 1992 Mar;51(3):366-71. doi: 10.1136/ard.51.3.366. PMID 1533506
• van der Heijden GJ. Shoulder disorders: a state-of-the-art review. Baillieres Best Pract Res Clin Rheumatol. 1999 Jun;13(2):287-309. doi: 10.1053/berh.1999.0021. PMID 10952865
• Luime JJ, Koes BW, Hendriksen IJ, Burdorf A, Verhagen AP, Miedema HS, Verhaar JA. Prevalence and incidence of shoulder pain in the general population; a systematic review. Scand J Rheumatol. 2004;33(2):73-81. doi: 10.1080/03009740310004667. PMID 15163107
• Bot SD, van der Waal JM, Terwee CB, van der Windt DA, Schellevis FG, Bouter LM, Dekker J. Incidence and prevalence of complaints of the neck and upper extremity in general practice. Ann Rheum Dis. 2005 Jan;64(1):118-23. doi: 10.1136/ard.2003.019349. PMID 15608309
• Linsell L, Dawson J, Zondervan K, Rose P, Randall T, Fitzpatrick R, Carr A. Prevalence and incidence of adults consulting for shoulder conditions in UK primary care; patterns of diagnosis and referral. Rheumatology (Oxford). 2006 Feb;45(2):215-21. doi: 10.1093/rheumatology/kei139. Epub 2005 Nov 1. PMID 16263781
• Hartvigsen J, Davidsen M, Hestbaek L, Sogaard K, Roos EM. Patterns of musculoskeletal pain in the population: a latent class analysis using a nationally representative interviewer-based survey of 4817 Danes. Eur J Pain. 2013 Mar;17(3):452-60. doi: 10.1002/j.1532-2149.2012.00225.x. Epub 2012 Oct 5. PMID 23042697
• Peters D, Davies P, Pietroni P. Musculoskeletal clinic in general practice: study of one year's referrals. Br J Gen Pract. 1994 Jan;44(378):25-9. PMID 8312034
• van der Windt DA, Koes BW, de Jong BA, Bouter LM. Shoulder disorders in general practice: incidence, patient characteristics, and management. Ann Rheum Dis. 1995 Dec;54(12):959-64. doi: 10.1136/ard.54.12.959. PMID 8546527

Identifiers

NCT: NCT05327972 · APHP210416

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗