Arimoclomol in Sporadic Inclusion Body Myositis

Study Overview
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Brief Summary
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Inclusion body myositis (IBM) is the most common progressive and debilitating muscle disease beginning in persons over 50 years of age. This study will assess the safety and tolerability of Arimoclomol in IBM as compared to placebo over 4 months of treatment.

Detailed Description
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IBM is a chronic disorder in which muscles become inflamed (swollen) and cause muscle weakening. The cause is unknown. There is new evidence to suggest that the pathology in IBM results from cellular changes induced by a variety of stressful events and diseases. In response to these stressful events the body's normal response is to increase the levels of Heat Shock Proteins (HSP) to help counteract and stop these cellular changes. In people with IBM this increase does not appear sufficient enough to reverse these toxic cellular changes. Arimoclomol causes the body to make more of this HSP protein. By increasing HSP levels in IBM patients we hope to reverse the toxic cellular changes that might be responsible for the pathology of IBM.

Official Title
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Safety and Tolerability Trial of Arimoclomol for Sporadic Inclusion Body Myositis

Conditions
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Inclusion Body Myositis

Intervention / Treatment
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* Drug: Arimoclomol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the diagnostic criteria for definite or probable IBM (Griggs 1995) Muscle function adequate for quantitative muscle testing Age > 50 years Women must be postmenopausal or status post hysterectomy For any patient currently taking medication for IBM, they must remain on current dosage for the extent of the study and last dosage change must be > 30 days previous to enrollment Exclusion Criteria: Presence of any one of the following medical conditions: diabetes mellitus or patients taking anti-diabetic medications, chronic infection, chronic renal insufficiency, cancer other than skin cancer less than 5 years previously, multiple sclerosis or prior episode or central nervous system demyelination, or other chronic serious medical illnesses Presence of any of the following on routine blood screening: WBC < 3000, platelets < 100,000, hematocrit < 30%, BUN > 30 mg%, creatine > 1.5 mg%, symptomatic liver disease with serum albumin < 3 g/dl, PT or PTT > upper range of control values Women who are pregnant or lactating History of non-compliance with other therapies Coexistence of other neuromuscular disease Drug or alcohol abuse within the last 3 months Inability to give informed consent Known bleeding disorder Use of potentially renal toxic drugs Prior difficulties with local anesthetic

Ages Eligible for Study
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Minimum Age: 50 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 |
| --- | --- |
| Active Comparator: 1<br>Arimoclomol | Drug: Arimoclomol<br>* Arimoclomol 100 mg TID for 4 months<br>|
| Placebo Comparator: 2<br> | Other: Placebo<br>* Placebo for 4 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Adverse Events Reported | Measure reflects the total number of adverse events reported during course of the study. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heat Shock Protein 70 (HSP70) Levels in the Tissue | Biopsy taken from participants at baseline and month 4 visits. Measured change in HSP70 levels in the tissue. | Change from Baseline to Month 4 | 
| Muscle Strength Testing | Change in MMT score for the period. The MMT score range is 0-5. A score of 0 is the lowest and represents no visible or palpable contraction. A score of 5 is the highest and represents full range of motion against gravity, maximal resistance. | Change from Baseline to Month 4 | 
| Muscle Strength Testing | Change in MMT score for the period. The MMT score range is 0-5. A score of 0 is the lowest and represents no visible or palpable contraction. A score of 5 is the highest and represents full range of motion against gravity, maximal resistance. | Change from Baseline to Month 8 | 
| Muscle Strength Testing | Change in MMT score for the period. The MMT score range is 0-5. A score of 0 is the lowest and represents no visible or palpable contraction. A score of 5 is the highest and represents full range of motion against gravity, maximal resistance. | Change from Baseline to Month 12 | 
| Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score | Measured change for the period. The questionnaire has 10 questions. The maximum score is 40. The higher the score the better the functional status of the patient. | Change from Baseline to Month 4 | 
| Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score | Measured change for the period. The questionnaire has 10 questions. The maximum score is 40. The higher the score the better the functional status of the patient. | Change from Baseline to Month 8 | 
| Inclusion Body Myositis-Functional Rating Scale (IBMFRS) Score | Measured change for the period. The questionnaire has 10 questions. The maximum score is 40. The higher the score the better the functional status of the patient. | Change from Baseline to Month 12 | 
| Maximum Isometric Voluntary Contraction Testing (MVICT) Score | Measured MVICT using the Quantitative Muscle Assessment (QMA) system designed by Computer Source, Atlanta, GA. The system uses an adjustable cuff to attach the patient's arm or leg to an inelastic strap that is connected to force transducer with a load of 0.5 to 1,000 Newtons. Maximum force is recorded. | Change from Baseline to Month 4 | 
| Maximum Isometric Voluntary Contraction Testing (MVICT) Score | Measured MVICT using the Quantitative Muscle Assessment (QMA) system designed by Computer Source, Atlanta, GA. The system uses an adjustable cuff to attach the patient's arm or leg to an inelastic strap that is connected to force transducer with a load of 0.5 to 1,000 Newtons. Maximum force is recorded. | Change from Baseline to Month 8 | 
| Maximum Isometric Voluntary Contraction Testing (MVICT) Score | Measured MVICT using the Quantitative Muscle Assessment (QMA) system designed by Computer Source, Atlanta, GA. The system uses an adjustable cuff to attach the patient's arm or leg to an inelastic strap that is connected to force transducer with a load of 0.5 to 1,000 Newtons. Maximum force is recorded. | Change from Baseline to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myositis, IBM, inclusion body myositis