Muscle-Related Side Effects of Statins: Functional Impact, Mechanisms, and Potential Relief With Vitamin D Supplementation

Study Overview
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Brief Summary
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This proposal will explore muscle function (strength and endurance) in men and women suffering from statin-induced muscle symptoms. The mechanisms responsible for these muscle symptoms will be explored. Also, the investigators will assess the potential usefulness of vitamin D supplementation in a randomized control trial.

Detailed Description
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Statins are a class of drugs that are widely prescribed to lower blood cholesterol levels. Although they have few side effects, many patients report muscle pain, cramps, and weakness when using these drugs. We know very little on the real impact of these muscle symptoms on patient quality of life, especially in relation to muscle strength and endurance. Patients under statin therapy will stop medication for 2 months. Results from blood sample, muscle function and muscle biopsy (in some participants) will be compared with baseline. Participants will then take vitamin D supplementation or placebo for one month. Thereafter, statin will be reintroduced for two months while continuing vitamin D or placebo supplementation. At the end of that time, measures from blood sample, muscle function and muscle biopsy will be compared with other visits.

Official Title
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Muscle-Related Side Effects of Statins: Functional Impact, Mechanisms, and Potential Relief With Vitamin D Supplementation

Conditions
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HMG COA Reductase Inhibitor Adverse Reaction

Intervention / Treatment
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* Drug: Vitamin D
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: statin therapy healthy and sedentary or moderately physical active Exclusion Criteria: Current treatment with other lipid-lowering drugs Natural medicine affecting lipid metabolism CK levels above the normal range Clinical vitamin D deficiency Impaired liver or kidney function Untreated hypo- or hyperthyroidism Treatment with other medications known to increase risk of myopathy Existing infection requiring antibiotic therapy Consumption of greater than 60 ml of grapefruit juice per day Inherited muscle disorders or myopathy Polymyositis or inflammatory myopathy Use of corticosteroids Comorbidities resulting in muscle or bone pain History of elevated CK Unexplained cramps Known sickle cell trait Cancer within the 5 years prior to study entry Diabetes Stroke, coronary artery or peripheral vascular disease Physical disability or previous injury interfering with exercise testing Pregnant or breastfeeding Depression (in last 3 years) or treatment with antidepressants Use of anti-psychotic drugs Alcohol abuse

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D<br> | Drug: Vitamin D<br>* Participants will receive weekly doses of 30,000 IU of vitamin D for 3 months.<br>* Other names: Cholecalciferol, D-tabs;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Participants will receive placebo (lactose 100 mg) for 3 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain score |  | Change from baseline at 2 months | 
| Change in muscle function testing | Strenght and endurance evaluation | Change from baseline at 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle histology | Histological, ultrastructural and metabolic assessment of muscle biopsy. | Change from baseline at 2 months | 
| Change in pain score |  | Change from baseline at 5 months | 
| Change in muscle function testing |  | Change from baseline at 5 months | 
| Change in muscle histology |  | Change from baseline at 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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statins, side effects, muscle, vitamin D, biopsy, strength, fatigue