Hypercholesterolemia, Statin-Associated Myopathy
Conditions
Keywords
Statin related myalgia, Hyperlipidemia, Red yeast rice, Cardiovascular Diseases, Nutritional and Metabolic Diseases
Brief summary
This study will examine the effect of red yeast rice extract compared to pravastatin on muscle related complaints in individuals with high cholesterol who have previously been unable to tolerate statin medications due to muscle pain. The study will determine whether red yeast is associated with a lower level of muscle related complaints compared to pravastatin.
Detailed description
20 million Americans are actively treated with statins at an annual cost of 16 billion dollars. Statins are effective therapeutic agents for reducing LDL cholesterol and have documented effectiveness. However, a significant subset of patients (5-18%), cannot tolerate lipid lowering statin therapy due to intolerable muscle-related symptoms characterized by muscle pain and/or weakness. These symptoms affect quality of life and lead to poor adherence. Patients may seek alternative therapies to manage hypercholesterolemia if they have been intolerant of statin therapy. One commonly used alternative treatment option is the Chinese herb red yeast rice extract. Several small studies performed in China, have suggested this treatment is efficacious and well tolerated. In the U.S. red yeast rice is sold over the counter a dietary supplement. The objective of this study is to critically examine the safety and efficacy of the Chinese herb red yeast rice as an alternative lipid lowering therapy, in a statin intolerant population. This objective will be operationalized by a double-blind randomized trial, comparing the effect of red yeast rice extract, to that of pravastatin on the level of myalgia in subjects with a prior history of statin-induced myalgias. The specific aims include: 1. Determine the relative rates of withdrawal from treatment in subjects receiving red yeast rice compared to pravastatin. 2. Determine if red yeast rice is associated with a lower level of muscle pain (myalgia) symptoms compared to pravastatin as measured by the Brief Pain Inventory, a validated pain questionnaire. 3. Determine if red yeast rice is associated with a lower level of muscle weakness compared to pravastatin as measured by a dynamometry, a validated muscle strength testing method.
Interventions
DIETARY_SUPPLEMENTRed Yeast Rice
Four 600mg capsules twice daily for 12 weeks
DRUGPravastatin
One 20mg capsule twice daily for 12 weeks
BEHAVIORALLifestyle modification program
Weekly sessions each lasting 3 1/2 hours for 12 weeks
Sponsors
Chestnut Hill Health System
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subject reports stopping at least one statin drug due to complaints of muscle pain or weakness which his/her physician thinks was attributable to the drug. * Subject has never taken pravastatin. * Subject willing to remain off the dietary supplements CoQ10, L-carnitine, fish oil, policosanol, and guggulipid, garlic, and phytosterols in margarines (e.g. Benecol, Promise activ), milk or cereal products, for one month prior to the trial and for the duration of the trial.
Exclusion criteria
* A history of muscle damage (CK\>1000 IU) on statin therapy. * A history of generalized chronic pain such as fibromyalgia, or generalized arthritis. * Any active cardiac problem including chest pain, angina, heart attack, bypass surgery, angioplasty/stent or unstable angina/acute coronary syndrome within the past 6 months. * Taking other lipid lowering drugs including: ezetimibe, gemfibrozil, niacin, fibrates or bile acid sequestrants. * Triglyceride level more than 400 mg/dl. * Taking weight loss medication including orlistat, sibutramine, diethylpropion, phendimetrazine, phentermine. * Taking pain medication or systemic steroids on a chronic basis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Withdrawal of Therapy Due to Muscle Symptoms That Are Either Intolerable and/or Associated With a Creatine Kinase(CK) >500 | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change in LDL-Cholesterol Measured at the Beginning and End of the Study | 12 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pravastatin | 22 |
| Red Yeast Rice | 21 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 |
Baseline characteristics
| Characteristic | Red Yeast Rice | Pravastatin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 8 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 14 Participants | 25 Participants |
| Age Continuous | 62.4 years STANDARD_DEVIATION 8.9 | 62.9 years STANDARD_DEVIATION 6.6 | 62.7 years STANDARD_DEVIATION 7.7 |
| Region of Enrollment United States | 21 participants | 22 participants | 43 participants |
| Sex: Female, Male Female | 16 Participants | 16 Participants | 32 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 22 | 11 / 21 |
| serious Total, serious adverse events | 0 / 22 | 0 / 21 |
Outcome results
Primary
Withdrawal of Therapy Due to Muscle Symptoms That Are Either Intolerable and/or Associated With a Creatine Kinase(CK) >500
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pravastatin | Withdrawal of Therapy Due to Muscle Symptoms That Are Either Intolerable and/or Associated With a Creatine Kinase(CK) >500 | 2 Participants |
| Red Yeast Rice | Withdrawal of Therapy Due to Muscle Symptoms That Are Either Intolerable and/or Associated With a Creatine Kinase(CK) >500 | 1 Participants |
Secondary
Change in LDL-Cholesterol Measured at the Beginning and End of the Study
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pravastatin | Change in LDL-Cholesterol Measured at the Beginning and End of the Study | -27.0 Percentage Change | Standard Deviation 15.4 |
| Red Yeast Rice | Change in LDL-Cholesterol Measured at the Beginning and End of the Study | -30.2 Percentage Change | Standard Deviation 10.5 |