Is Myopathy Part of Statin Therapy (IMPOSTER-16)

Study Overview
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Brief Summary
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There is a significant proportion of patients complaining of muscle symptoms while on statin therapy who have a measurable difference in muscle strength or endurance and whose muscle biopsies are diagnostic for myopathy.

Detailed Description
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This is a double-blinded, randomized, placebo-controlled, crossover trial. Sixty patients who are identified by their physician as having muscle pain or weakness while on statin therapy and in whom creatine kinase (CK) enzyme determinations have been normal will be enrolled voluntarily. All patients will have a percutaneous muscle biopsy prior to enrollment into the trial. These patients will be randomized in a blinded crossover fashion to either standardized statin therapy or placebo in eight week intervals. After eight weeks of drug or placebo the patients will be assessed for signs and symptoms of muscle weakness by: Dynamometry of grip and hip strength An exercise test with exhaled gas analysis Blood tests for cholesterol, creatine kinase, lactate Urine tests for organic acids Following the first eight-week study and testing period, each patient will serve as their own control and they will enter a second eight-week study period. During the second phase they will take the opposite therapy, either drug or placebo, which they have not yet received. Sub-studies will include ten controls who have never previously received statins and ten subjects who have suffered statin-induced rhabdomyolysis. Subjects in these sub-studies will not be exposed to statin therapy and will only undergo limited testing.

Official Title
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Double Blind, Prospective Randomized, Crossover Study of Patients With Muscle Complaints on Statin Therapy

Conditions
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Myopathic Conditions

Intervention / Treatment
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* Drug: cellulose placebo vs. atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary doctor's permission Patient understands nature of study and has signed consent Patient is >21 years of age Patient willing to stop statin for up to 12 weeks and remain off CoQ10 for study duration Patient able to perform the strength and functional tests required Patient complains of muscle weakness or aching which he/she or his/her physician feels may be attributable to statin therapy CK < 350 IU Thyroid stimulating hormone (TSH) must be normal Fasting respiratory exchange ratio (RER) > 0.80 off statin for at least 4 weeks Exclusion Criteria: Severe underlying illness including: Cr > 3.0, liver failure, unstable angina, symptomatic valvular heart disease, congestive heart failure, or prior cerebrovascular accident (CVA) preventing exercise testing. History of muscle damage (CK > 350 IU) on statins Underlying musculoskeletal disorder preventing muscle testing History of severe depression Taking doses of other medicines with statin sufficient to cause myopathy including: cyclosporine, erythromycin or other macrolide antibiotics; fluconazole; niacin; fibrates; or > 16 oz. of grapefruit juice daily. Diabetes requiring other than diet therapy Use of thiazolidinediones (TZD's), protease inhibitors or other drugs known to influence RER or fatty acid oxidation. Abnormal thyroid status Inability to maintain constant exercise, dietary, and drug regimen during the 16 weeks required by the study protocol.

Ages Eligible for Study
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Minimum Age: 21 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: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: cellulose placebo vs. atorvastatin<br>* drug<br>* Other names: atorvastatin;|
| Active Comparator: 2<br>statin administration | Drug: cellulose placebo vs. atorvastatin<br>* drug<br>* Other names: atorvastatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hip flexion |  | 8 weeks | 
| oxygen consumption and anaerobic threshold |  | 8 weeks | 
| muscle pathology score |  | at entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ability to identify blinded statin |  | 8 weeks | 
| other aerobic exercise indexes |  | 8 weeks | 
| fatty acid oxidation of myocyte cell cultures |  | at entry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rhabdomyolysis,, myositis,, myopathy,, statin side effects,, fatty acid oxidation, Statin induced Muscle toxicity