Quality of Life in Patients With Statin-Associated Myopathy

Phase 4

Terminated

Conditions: Statin Adverse Reaction

Interventions: Drug: Placebo
Drug: Statins

Registration Number: NCT00850460

Lead Sponsor: Rockefeller University

Brief Summary: The proposed study will focus on possible effects of statins on muscle strength and why they become tired more easily, quality of life, and measurements to understand why muscles are not able to fully utilize fats. The investigators are specifically interested in statin users and the impact of muscle symptoms on daily activities and quality of life.

This study hypothesize that patients with likely statin-associated myopathy have a metabolic dysregulation in fuel utilization such that compared to patients continuing statins, those on placebo will show:

1. improved Individualized Neuromuscular Quality of Life (INQoL) and Short Form-36 (SF-36) scores (primary end point)

2. alleviation of muscle symptoms,

3. increased utilization of fatty acids as a fuel source reflected by the metabolic test results

4. decreased intramyocellular lipid (IMCL)

5. improved insulin sensitivity.

Detailed Description: The proposed study will focus on possible effects of statins on muscle strength and quality of life, and measurements to understand why muscles of statin users are not able to fully utilize fats. The investigators are specifically interested in statin users and the impact of muscle symptoms on daily activities and quality of life.

This study hypothesizes that patients with likely statin-associated myopathy have a metabolic dysregulation in fuel utilization such that compared to patients continuing statins, those on placebo will show:

1. improved INQoL and SF-36 scores (primary end point)

2. alleviation of muscle symptoms,

3. increased utilization of fatty acids as a fuel source reflected by the metabolic test results

4. decreased IMCL

5. improved insulin sensitivity.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 14

Inclusion Criteria

males and females 30-60 yrs old
experiencing muscle pain, weakness, numbness or cramping that they perceive to interfere with activities of daily living (ADLs), but able to ambulate independently (in order to perform exercise tests)
muscle symptoms started/ occurred within one year of starting statin treatment or within one year of changing statin brand or dose adjustment
currently taking a statin (has been taking medications ≥ 80% of the time or at least 5 days/week)
≤ 15% probability of having a cardiovascular (CV) event in the next 10 years calculated using an online CV risk calculator (while on current statin) for the questionnaire portion; AND with a low or a moderate American College of Sports Medicine (ACSM) risk stratification for a cardiovascular event during a treadmill test for the full metabolic study
must agree to have a letter sent to inform the health care provider who prescribed the statin of study participation except for subjects referred by Metropolitan Hospital physicians

Exclusion Criteria

concomitant treatment with other lipid-lowering agents
impaired liver or kidney function ( alanine aminotransferase (ALT) or asparate aminotransferase (AST) ≥ 3x upper limit of normal, creatinine ≥ 3x or creatine phosphokinase (CPK) ≥ 5x upper limit of normal)
untreated hypo or hyperthyroidism
current treatment with other medications known to increase risk of myopathy (e.g. cyclosporine, azithromycin, erythromycin and other macrolide antibiotics, azole antifungals, fusidic acid, digoxin)
documented history of muscle disorder or myopathy other than statin-associated myopathy
anemia (Hb< 110 g/dL)
cancer within 5 years of enrollment except basal or squamous cell carcinoma (CA) of the skin
diabetes
HIV-1 infection
Uncontrolled blood pressure ≥ 160/100
known coronary artery disease or peripheral vascular disease
chronic illnesses such as lupus, rheumatoid arthritis, psoriasis
any condition, that at the investigators' discretion would impact/ bias the study data
long term oral, nasal, or inhaler steroid use > 6 months
on Hormone Therapy except for thyroid replacement
alcohol consumption ≥ 40 g/day (3 glasses/day wine or beers or binge drinking ≥ 4 glasses/night)
engaged in significant amounts of sport or strenuous leisure activity (> 60 min four times per week)
surgery in the past 6 months except for minor excision/incision procedures,
12-L electrocardiogram demonstrating old/new myocardial infarction/ ischemia or other findings that, at the cardiologist's discretion, may put the subject at high risk
cognitive impairment that prevents comprehension of questionnaires
inability to read English (questionnaire language)

Exclusions for the metabolic study:

currently taking beta blockers
body mass index > 28 kg/m2
premenopausal females < 50 yrs (menopause defined as 12 consecutive months without menstruation (in order to avoid the confounding effect of the menstrual cycle phase on fuel selection)
physical disability or previous injury that prevents safe exercise testing
do not meet the magnetic resonance spectroscopy (MRS) prescreening criteria

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Lactose placebo pill
Statins	Statins	Statin medications

Primary Outcome Measures

Name	Time	Method
Individualized Neuromuscular Quality of Life (INQoL) Mean Scores From Week 0 to Week 8	Week 0 to Week 8	Scores from the self-administered INQoL questionnaire will be compared at the start of the study (Week 0) and at the end (Week 8) between the statin-treated group and the placebo group. Scores range from 0-100, with 100 being a better outcome. Measures reported are the means of Week 0 and week 8, measures of dispersion is the range of the results (3 per group).
Individualized Short Form-36 (SF-36) Mean Scores (Physical Component) From Week 0 to Week 8	Week 0 to Week 8	Scores from the self-administered SF-36 (Physical component) questionnaire were measured at the start (Week 0) of the study and at the end (Week 8) among patients in the placebo- and statin-treated group. Mean scores range from 0 (minimum) - 100 (maximum) with higher mean scores reflecting better outcomes. Measures reported are the means of Week 0 and week 8, measures of dispersion is the range of scores.

Secondary Outcome Measures