Cramps, HMG COA Reductase Inhibitor Adverse Reaction, Myalgia or Myositis Nos, Pain, Weakness
Conditions
Keywords
CoQ10, Statins, Myalgia, Muscle Pain, Muscle Weakness
Brief summary
This study will evaluate whether a dietary supplement, coenzyme Q10 (CoQ10), will improve muscle symptoms, such as muscle aches, pains, cramps, and/or weakness, which are experienced by some individuals who use statin medications.
Detailed description
This study will recruit individuals who have had muscle symptoms while using a statin. During the first part of the study, volunteers will be given a statin medication to see if their muscle symptoms return. Those who experience muscle symptoms on this statin rechallenge will be invited to continue in the second part of the trial, in which participants will be randomly assigned to receive either CoQ10 or a placebo (sugar pill) to take with statin medication. We hypothesize that those who receive CoQ10 will experience an improvement in their muscle symptoms compared to those who receive placebo, and, secondarily, that those who receive CoQ10 will be more likely to continue taking the statin medication.
Interventions
DIETARY_SUPPLEMENTCoenzyme Q10
300 mg of CoQ10 (three 100 mg chewable tablets) 2 times daily for 4 weeks
OTHERPlacebo
Placebo (three chewable tablets) 2 times daily for 4 weeks
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Catherine Buettner
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Patients with a history of muscle symptoms (such as aches, pains, cramps and/or weakness) while taking a statin drug that persisted for at least 2 weeks on a statin
Exclusion criteria
* Plasma creatine kinase levels \> 3 times the upper normal limit * Liver enzymes, alanine transferase (ALT) or aspartate transferase (AST) \> 2 times the upper normal limit * Pregnancy or breastfeeding (a contraindication for statin use) * Severe renal impairment, defined as glomerular filtration rate (GFR) \< 30 ml/min/1.73 m2 * Bleeding disorder, current use of warfarin, an international normalized ratio (INR) greater than 1.5, or a platelet count less than 100,000 mm3 * Contraindication to strength testing, including myocardial infarction, unstable angina, or revascularization procedure within the past six weeks, a history of brain aneurysm or stroke * Chest or abdominal surgery within the past six weeks * Severe persistent pain related to other causes * Unable to complete self-administered questionnaires, or unable to read or converse in English
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Reduction in Muscle Pain Associated With Statin Use | 4 weeks | Clinically significant pain reduction was defined, a priori, as a reduction \> 1.5 points on the Brief Pain Inventory-Severity Scale (BPI-SS), range: 0 to 10 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Continuation of Statin | 4 weeks | Adherence of statin use was defined a priori as participant using Simvastatin 20 mg /day at the end of 4 weeks and having used \>85% of statin doses. |
| Percentage of Participants With Improvement in Disability Related to Muscle Pain | 4 weeks | Disability improvement was based on patient report of improvement they felt was meaningful to them |
| Percentage of Participants With Adverse Effects | 4 weeks | serious adverse effects and possible side effects were tracked through all phases of the study by participant interview and checklist at each visit, up to 4 weeks. |
Countries
United States
Participant flow
Recruitment details
Persons with a history of statin myalgia were recruited from the greater Boston area using flyers, ads, and announcements to seek volunteers. A history of statin myalgia was defined as having muscle symptoms thought to be due to a statin, with symptoms that began after a statin was started and that persisted for at least 2 weeks while using statin.
Pre-assignment details
Confirmation of statin myalgia was based on completing a statin washout, and statin rechallenge. On washout, improvement of symptoms within 2 months was required to advance. On rechallenge, simvastatin 20 mg daily was given, and only those with return of symptoms within 3 months were randomized. Out of 68 participants enrolled, 39 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Coenzyme Q10 CoQ10 300 mg 2 x daily + Simvastatin 20 mg daily | 19 |
| Placebo Placebo 2 x daily + Simvastatin 20 mg daily | 20 |
| Total | 39 |
Baseline characteristics
| Characteristic | Placebo | Total | Coenzyme Q10 |
|---|---|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 11.2 | 61.0 years STANDARD_DEVIATION 9.7 | 62.0 years STANDARD_DEVIATION 7.9 |
| Alcohol Servings/Day 0 to 1 | 8 participants | 16 participants | 8 participants |
| Alcohol Servings/Day 2 to 4 | 9 participants | 18 participants | 9 participants |
| Alcohol Servings/Day 5 or more | 3 participants | 5 participants | 2 participants |
| Diabetes No | 16 participants | 30 participants | 14 participants |
| Diabetes Yes | 4 participants | 9 participants | 5 participants |
| Exercise Moderate/Vigorous | 8 participants | 18 participants | 10 participants |
| Exercise None/Light | 12 participants | 21 participants | 9 participants |
| Gender Female | 6 Participants | 20 Participants | 14 Participants |
| Gender Male | 14 Participants | 19 Participants | 5 Participants |
| Hypertension No | 4 participants | 9 participants | 5 participants |
| Hypertension Yes | 16 participants | 30 participants | 14 participants |
| Pain (baseline) visual analog scale (0-10) | 4.9 units on a scale STANDARD_DEVIATION 1.9 | 4.6 units on a scale STANDARD_DEVIATION 2 | 4.4 units on a scale STANDARD_DEVIATION 2.2 |
| Race/Ethnicity, Customized Non-Hispanic White | 17 participants | 34 participants | 17 participants |
| Race/Ethnicity, Customized Other | 3 participants | 5 participants | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 19 | 2 / 20 |
| serious Total, serious adverse events | 0 / 19 | 0 / 20 |
Outcome results
Primary
Percentage of Participants With Reduction in Muscle Pain Associated With Statin Use
Clinically significant pain reduction was defined, a priori, as a reduction \> 1.5 points on the Brief Pain Inventory-Severity Scale (BPI-SS), range: 0 to 10
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Coenzyme Q10 | Percentage of Participants With Reduction in Muscle Pain Associated With Statin Use | 53 % of participants with pain reduction |
| Placebo | Percentage of Participants With Reduction in Muscle Pain Associated With Statin Use | 65 % of participants with pain reduction |
Secondary
Continuation of Statin
Adherence of statin use was defined a priori as participant using Simvastatin 20 mg /day at the end of 4 weeks and having used \>85% of statin doses.
Time frame: 4 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Coenzyme Q10 | Continuation of Statin | Adherent with Statin at 4 wks | 17 participants |
| Coenzyme Q10 | Continuation of Statin | Not Adherent with Statin at 4 wks | 2 participants |
| Placebo | Continuation of Statin | Adherent with Statin at 4 wks | 18 participants |
| Placebo | Continuation of Statin | Not Adherent with Statin at 4 wks | 2 participants |
Secondary
Percentage of Participants With Adverse Effects
serious adverse effects and possible side effects were tracked through all phases of the study by participant interview and checklist at each visit, up to 4 weeks.
Time frame: 4 weeks
Population: 3 serious adverse events occurred during the study that were judged unrelated to the study: specifically, 3 participants were hospitalized prior to randomization, 1 for pneumonia; 1 for a back injury; and 1 for a mental health condition. All recovered. There were no SAE during the randomization period. Non serious AEs are listed below.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Coenzyme Q10 | Percentage of Participants With Adverse Effects | Nausea/dyspepsia | 21 % of participants reporting |
| Coenzyme Q10 | Percentage of Participants With Adverse Effects | Fatigue | 10 % of participants reporting |
| Placebo | Percentage of Participants With Adverse Effects | Fatigue | 10 % of participants reporting |
| Placebo | Percentage of Participants With Adverse Effects | Nausea/dyspepsia | 10 % of participants reporting |
Secondary
Percentage of Participants With Improvement in Disability Related to Muscle Pain
Disability improvement was based on patient report of improvement they felt was meaningful to them
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Coenzyme Q10 | Percentage of Participants With Improvement in Disability Related to Muscle Pain | 36 % reporting improved function |
| Placebo | Percentage of Participants With Improvement in Disability Related to Muscle Pain | 40 % reporting improved function |