Rapamycine vs Placebo for the Treatment of Inclusion Body Myositis

Study Overview
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Brief Summary
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Sporadic Inclusion Body Myositis (IBM) is the most frequent inflammatory myopathy in patients over 50. It is a slowly progressive, but today untreatable (notably by classical immunosuppressants) disease. Rapamycin used in organ transplantation blocks the activity of T effector cells, preserves T regulatory cells and induces autophagy (protein degradation), all parameters impaired during IBM. RAPAMI is a prospective, randomised, controlled, double blind, monocentric, phase IIb trial evaluating rapamycine against placebo.

Official Title
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Étude de l'Effet de la Rapamycine Sur la Force Musculaire et la réponse Immunitaire au Cours de la Myosite à Inclusions: étude RAPAMI

Conditions
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Inclusion Body Myositis (IBM)

Intervention / Treatment
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* Drug: Rapamycin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: IBM defined by the Benveniste & Hilton-Jones ( Neuromuscul Disord. 2010;20: 414-21) or Llyod criteria (Neurology 2014; 83: 426-433) Exclusion Criteria: Impossiblility to walk 10 meters Hypersensitivity to rapamycin or one compound of the oral solution Severe respiratory insufficiency (FVC < 50% and/or FEV1 < 50%) Severe chronic kidney disease (Estimated Glomerular Filtration Rate < 15 ml/min and/or proteinuria > 0.3 g/24h) Chronic liver disease (cirrhosis and/or ALT/AST > 2.5 normal values) Cancer non in remission (necessitating specific treatment) during the past 12 months Connective Tissue Disease non in remission (necessitating specific treatment) during the past 12 months Pregnancy Seropositivity for HIV, HCV or HBV Total cholesterolemia > 8 mmol/l Triglyceridemia > 5 mmol/l Hemoglobinemia < 11 g/dL Thrombopenia < 100 000/mm3 Neutropenia < 1500/ mm3 Lymphopenia < 1000/ mm3

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 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: Rapamycin<br>rapamycin 1 mg/ml oral solution, 2 mg/day (2 ml/day), once a day, during one year | Drug: Rapamycin<br>* Experimental: rapamycin oral solution, 2 mg/day during one year Comparator: placebo<br>* Other names: Rapamune;|
| Placebo Comparator: Placebo<br>Placebo oral solution, 2 ml/day, once a day, during one year | Drug: Placebo<br>* Comparator: placebo<br>* Other names: Phosal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| stabilization of quadiceps strength measured by myometry |  | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| stabilization of hand grip strength measured by myometry |  | 52 weeks | 
| comparison of 6 minutes walking test |  | 52 weeks | 
| composite measure of the handicap | Rivermead Mobility Index (RMI), scale Walton, Inclusion Body Myositis Weakness Composite Index (IBMWCI), Inclusion Body Myositis Functional rating scale (IBMFRS) | 52 weeks | 
| Quality of life by different scales | Health Assessment Questionnaire (HAQ), Instrumental activities of daily living (IADL),Individualized Neuromuscular Quality of Life Questionnaire (INQol) | 52 weeks | 
| measures of muscle fatty replacement by MRI |  | 52 weeks | 
| Measure of the tolerance | Efficacy will be measured by: check list of the known side effect of rapamycin. | 52 weeks | 
| measure of inflammation by MRI |  | 52 weeks |