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

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.

Study Overview

• Status: Completed
• Conditions: HMG COA Reductase Inhibitor Adverse Reaction
• Intervention / Treatment: Drug: Vitamin D; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Québec, Quebec, Canada, G1V 4G2
      • Centre hospitalier universitaire de Québec - CHUL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CHU de Quebec-Universite Laval
• Collaborators: Canadian Institutes of Health Research (CIHR); Laval University
• Investigators: Principal Investigator: Denis R Joanisse, PhD, Laval University; Principal Investigator: Jean Bergeron, MD, CHU de Quebec-Universite Laval; Principal Investigator: Jérôme Frenette, PhD, CHU de Quebec-Universite Laval

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: November 29, 2011
• First Submitted That Met QC Criteria: December 14, 2011
• First Posted (Estimate): December 16, 2011

Study Record Updates

• Last Update Posted (Estimate): January 27, 2016
• Last Update Submitted That Met QC Criteria: January 26, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: fatigue; muscle; vitamin D; strength; statins; side effects; biopsy
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: MOP 114917