Statin Adverse Reaction
Conditions
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.
Interventions
DRUGStatins
Subjects will be randomized to continue their statin dosage or placebo for 8 weeks. They will stay on the same dosage as prescribed by their physician. Usual dosage for atorvastatin 10-80 mg/tab once daily by mouth; simvastatin 20-80 mg/tab once daily by mouth; pravastatin 10-80 mg/tab once daily by mouth; rosuvastatin 5-20 mg/tab once daily by mouth.
DRUGPlacebo
Placebo pills will consist of lactose and will be given one capsule once daily
Sponsors
Cornell University
Adelphi University
Rockefeller University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Advertisements were placed (internet, radio, print) and a screening phone questionnaire was administered by study staff to determine potential inclusion. A collaboration with the Metropolitan Hospital (NY) was also established for potential referrals.
Pre-assignment details
Subjects in whom statins are possibly causative, using the World Health Organization (WHO)-Causality Assessment form, were invited to the outpatient clinic for 2 screening visits. Subjects found to be at high risk for cardiovascular events and those unwilling to be shifted to placebo were not enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Lactose placebo pill
Placebo: Placebo pills will consist of lactose and will be given one capsule once daily | 3 |
| Statins Statin medications
Statins: Subjects will be randomized to continue their statin dosage or placebo for 8 weeks. They will stay on the same dosage as prescribed by their physician. Usual dosage for atorvastatin 10-80 mg/tab once daily by mouth; simvastatin 20-80 mg/tab once daily by mouth; pravastatin 10-80 mg/tab once daily by mouth; rosuvastatin 5-20 mg/tab once daily by mouth. | 3 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 4 |
Baseline characteristics
| Characteristic | Placebo | Statins | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 6 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 3 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
Primary
Individualized Neuromuscular Quality of Life (INQoL) Mean Scores From 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).
Time frame: Week 0 to Week 8
Population: Three patients from each group completed the questionnaire portion of the study at Week 0 and Week 8.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Individualized Neuromuscular Quality of Life (INQoL) Mean Scores From Week 0 to Week 8 | Week 0 Mean Score | 65 units on a scale |
| Placebo | Individualized Neuromuscular Quality of Life (INQoL) Mean Scores From Week 0 to Week 8 | Week 8 Mean Score | 67 units on a scale |
| Statins | Individualized Neuromuscular Quality of Life (INQoL) Mean Scores From Week 0 to Week 8 | Week 0 Mean Score | 76 units on a scale |
| Statins | Individualized Neuromuscular Quality of Life (INQoL) Mean Scores From Week 0 to Week 8 | Week 8 Mean Score | 50 units on a scale |
Primary
Individualized Short Form-36 (SF-36) Mean Scores (Physical Component) From 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.
Time frame: Week 0 to Week 8
Population: Three patients from each group completed the questionnaire portion of the study at Week 0 and Week 8.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Individualized Short Form-36 (SF-36) Mean Scores (Physical Component) From Week 0 to Week 8 | Week 8 Mean Score | 56 units on a scale |
| Placebo | Individualized Short Form-36 (SF-36) Mean Scores (Physical Component) From Week 0 to Week 8 | Week 0 Mean Score | 50 units on a scale |
| Statins | Individualized Short Form-36 (SF-36) Mean Scores (Physical Component) From Week 0 to Week 8 | Week 0 Mean Score | 53 units on a scale |
| Statins | Individualized Short Form-36 (SF-36) Mean Scores (Physical Component) From Week 0 to Week 8 | Week 8 Mean Score | 48 units on a scale |