Is Myopathy Part of Statin Therapy (IMPOSTER-16)

This study has been terminated.
(Lack of funding)
Sponsor:
Information provided by:
Scripps Health
ClinicalTrials.gov Identifier:
NCT00127335
First received: August 4, 2005
Last updated: July 26, 2011
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Myopathic Conditions
Drug: cellulose placebo vs. atorvastatin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Diagnostic
Official Title: Double Blind, Prospective Randomized, Crossover Study of Patients With Muscle Complaints on Statin Therapy

Resource links provided by NLM:


Further study details as provided by Scripps Health:

Primary Outcome Measures:
  • hip flexion [ Time Frame: 8 weeks ]
  • grip strength [ Time Frame: 8 weeks ]
  • oxygen consumption and anaerobic threshold [ Time Frame: 8 weeks ]
  • muscle pathology score [ Time Frame: at entry ]

Secondary Outcome Measures:
  • ability to identify blinded statin [ Time Frame: 8 weeks ]
  • other aerobic exercise indexes [ Time Frame: 8 weeks ]
  • fatty acid oxidation of myocyte cell cultures [ Time Frame: at entry ]

Estimated Enrollment: 60
Study Start Date: August 2005
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1 Drug: cellulose placebo vs. atorvastatin
drug
Other Name: atorvastatin
Active Comparator: 2
statin administration
Drug: cellulose placebo vs. atorvastatin
drug
Other Name: 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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00127335

Locations
United States, California
Scripps Mercy Hospital
San Diego, California, United States, 92103
Sponsors and Collaborators
Scripps Health
Investigators
Principal Investigator: Paul S Phillips, MD Scripps Health
Study Director: Harminder Sikand, PharmD Scripps Mercy
  More Information

Publications:
Responsible Party: Paul Phillips,, MD, Scripps Health - Scripps Mercy Hospital
ClinicalTrials.gov Identifier: NCT00127335     History of Changes
Other Study ID Numbers: M-05-001 (MER004241)
Study First Received: August 4, 2005
Last Updated: July 26, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Scripps Health:
rhabdomyolysis,
myositis,
myopathy,
statin side effects,
fatty acid oxidation
Statin induced Muscle toxicity

Additional relevant MeSH terms:
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014