Is Myopathy Part of Statin Therapy (IMPOSTER-16)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Myopathic Conditions
• Intervention / Treatment: Drug: cellulose placebo vs. atorvastatin

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • Scripps Mercy Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1	Drug: cellulose placebo vs. atorvastatin; drug; Other Names: atorvastatin
Active Comparator: 2; statin administration	Drug: cellulose placebo vs. atorvastatin; drug; Other Names: atorvastatin

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Scripps Health
• Investigators: Principal Investigator: Paul S Phillips, MD, Scripps Health; Study Director: Harminder Sikand, PharmD, Scripps Mercy

Publications and helpful links

General Publications

• Phillips PS, Haas RH, Bannykh S, Hathaway S, Gray NL, Kimura BJ, Vladutiu GD, England JD; Scripps Mercy Clinical Research Center. Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med. 2002 Oct 1;137(7):581-5. doi: 10.7326/0003-4819-137-7-200210010-00009.
• Phillips PS. Ezetimibe and statin-associated myopathy. Ann Intern Med. 2004 Oct 19;141(8):649. doi: 10.7326/0003-4819-141-8-200410190-00021. No abstract available.
• Phillips PS, Phillips CT, Sullivan MJ, Naviaux RK, Haas RH. Statin myotoxicity is associated with changes in the cardiopulmonary function. Atherosclerosis. 2004 Nov;177(1):183-8. doi: 10.1016/j.atherosclerosis.2004.06.014.
• Antons KA, Williams CD, Baker SK, Phillips PS. Clinical perspectives of statin-induced rhabdomyolysis. Am J Med. 2006 May;119(5):400-9. doi: 10.1016/j.amjmed.2006.02.007.

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: August 4, 2005
• First Submitted That Met QC Criteria: August 4, 2005
• First Posted (Estimate): August 5, 2005

Study Record Updates

• Last Update Posted (Actual): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 21, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: myositis,; fatty acid oxidation; rhabdomyolysis,; myopathy,; statin side effects,; Statin induced Muscle toxicity
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Muscular Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: M-05-001 (MER004241)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO