Clinical trial NCT00127335: Is Myopathy Part of Statin Therapy (IMPOSTER-16)
Official title: Double Blind, Prospective Randomized, Crossover Study of Patients With Muscle Complaints on Statin Therapy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Myopathic Conditions
Keywords: rhabdomyolysis,
myositis,
myopathy,
statin side effects,
fatty acid oxidation
Statin induced Muscle toxicity
Lead sponsor: Scripps Health
Sponsor class: OTHER
First posted: 2005-08-05
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: hip flexion
timeFrame: 8 weeks
measure: oxygen consumption and anaerobic threshold
timeFrame: 8 weeks
measure: muscle pathology score
timeFrame: at entry
Secondary outcomes:
measure: ability to identify blinded statin
timeFrame: 8 weeks
measure: other aerobic exercise indexes
timeFrame: 8 weeks
measure: fatty acid oxidation of myocyte cell cultures
timeFrame: at entry
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Scripps Mercy Hospital
state: California
Study officials:
affiliation: Scripps Health
name: Paul S Phillips, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Scripps Mercy
name: Harminder Sikand, PharmD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.