Is Myopathy Part of Statin Therapy (IMPOSTER-16)

Myopathic Conditions Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00127335
• Other study ID #: M-05-001 (MER004241)
• Status: Withdrawn
• Phase: Phase 4
• Start date: August 2005
• Est. completion date: May 2008

Study information

• Verified date: November 2022
• Source: Scripps Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Muscular Diseases
• Myopathic Conditions

Intervention

Drug:
• cellulose placebo vs. atorvastatin
drug

Locations

Country	Name	City	State
United States	Scripps Mercy Hospital	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Scripps Health

Country where clinical trial is conducted

United States, 

References & Publications (4)

Antons KA, Williams CD, Baker SK, Phillips PS. Clinical perspectives of statin-induced rhabdomyolysis. Am J Med. 2006 May;119(5):400-9. Review. — View 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. — View 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. — View Citation

Phillips PS. Ezetimibe and statin-associated myopathy. Ann Intern Med. 2004 Oct 19;141(8):649. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	hip flexion		8 weeks
Primary	oxygen consumption and anaerobic threshold		8 weeks
Primary	muscle pathology score		at entry
Secondary	ability to identify blinded statin		8 weeks
Secondary	other aerobic exercise indexes		8 weeks
Secondary	fatty acid oxidation of myocyte cell cultures		at entry