Exercise-induced Muscle Damage in Statin Users

Completed

• Conditions: Cardiovascular Diseases; Muscle Damage; HMG COA Reductase Inhibitor Adverse Reaction
• Interventions: Other: Moderate-intensity exercise

• Registration Number: NCT05011643
• Lead Sponsor: Radboud University Medical Center

Brief Summary

Rationale: Combining statin treatment and physical activity is very effective for the prevention of cardiovascular diseases. Statins are well-tolerated by most patients, but may cause statin-associated muscle symptoms (SAMS) and elevated markers of skeletal muscle damage in some patients.

Several studies have shown that statins augment increases in serum creatine kinase after eccentric or vigorous exercise. If statins also increase muscle damage markers after exercises of moderate intensity is unclear. Symptomatic statin users may be more susceptible to exercise-induced skeletal muscle injury, however, previous studies did not differentiate between symptomatic and asymptomatic statin users.

Objective: To compare the impact of moderate-intensity exercise on muscle damage markers between symptomatic and asymptomatic statin users, and non-statin using controls. A secondary objective is to examine the association between leukocytes coenzyme Q10 levels and exercise-induced muscle damage and muscle complaints.

Detailed Description

Combining statin treatment and physical activity is very effective for the prevention of cardiovascular diseases. Statins are well-tolerated by most patients, but may cause statin-associated muscle symptoms (SAMS) and elevated markers of skeletal muscle damage in some patients.

Several studies have shown that statins augment increases in serum creatine kinase after eccentric or vigorous exercise. However. if statins also increase muscle damage markers after exercises of moderate intensity is unclear. Impaired mitochondrial oxidative function might contribute to SAMS and exercise-induced muscle damage. Several studies showed that statins decrease serum coenzyme Q10 levels, an essential component of the mitochondrial transport chain, but effects on intramuscular coenzyme Q10 levels are inconsistent. The investigators have observed that mitochondrial dysfunction is more pronounced in statin users with SAMS compared to asymptomatic statin users. This suggests that symptomatic statin users may be more susceptible to exercise-induced skeletal muscle injury. However, previous studies examining creatine kinase response to exercise did not differentiate between symptomatic and asymptomatic statin users.

In this cross-sectional observational study the investigators will study the impact of moderate-intensity exercise on muscle damage markers between symptomatic and asymptomatic statin users, and non-statin using controls. A secondary objective is to examine the association between leukocytes coenzyme Q10 levels and exercise-induced muscle damage and muscle complaints.

The investigators hypothesize that statins will not increase muscle damage markers after moderate-intensity exercise and that higher CoQ10 levels are associated with less exercise-induced muscle damage and muscle complaints.

Study Timeline

• Study Start: 2018-05-29
• Primary Completion: 2018-07-20
• Study Completion: 2018-07-20
• Status Verified: 2021-08
• Study First Submitted: 2021-08-15
• Study First Submitted QC: 2021-08-15
• Study First Posted: 2021-08-18
• Last Update Submitted: 2021-08-23
• Last Update Posted: 2021-08-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Mentally able to give informed consent
• Statin groups: statin treatment for at least 3 months

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Exclusion Criteria

• Known hereditary muscle defect
• Known mitochondrial disease
• Diabetes Mellitus
• Hypo- or hyperthyroidism
• Other diseases known to cause muscle symptoms (e.g. m. Parkinson or rheumatic diseases)
• Coenzyme Q10 supplementation

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Asymptomatic statin users	Moderate-intensity exercise	Statin users without muscle symptoms
Non-statin using controls	Moderate-intensity exercise	Participants not using statins
Symptomatic statin users	Moderate-intensity exercise	Statin users with self-reported muscle symptoms

Primary Outcome Measures

Name	Time	Method
Muscle damage markers	Baseline (before exercise) and after three days of moderate-intensity walking exercise (measured each day)	Change in muscle damage markers (creatine kinase, myoglobin, lactate dehydrogenase, troponin I and BNP) from baseline to post-exercise

Secondary Outcome Measures

Name	Time	Method
Muscle pain scores	Baseline (before exercise) and after three days of moderate-intensity walking exercise (measured each day)	Muscle pain scores measured with the Brief Pain Inventory questionnaire (10 point scale with 0 representing no pain and 10 the worst pain imaginable)
Muscle strength and fatigue	Baseline (before exercise) and after one day of moderate-intensity walking exercise	M. Quadriceps muscle strength and fatigue measured using electrical stimulation
Coenzyme Q10 levels	At baseline	Coenzyme Q10 levels measured in leukocytes

Trial Locations

Locations (1)

Department of Physiology; 🇳🇱 Nijmegen, Netherlands