Pharmacogenomic Modulators of Impaired Exercise Adaptation in Statin Users

N/AActive Not RecruitingNCT04636138

University of Kansas Medical Center5 enrolled

Overview

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have beneficial effects (prevent stroke, heart attack) but also some bad ones (block some good effects of exercise). Individuals have genetic variations in proteins that metabolize/transport statins. The investigators hypothesize that these variations modulate the relationship between statin use and lack of benefit from exercise. The investigators will test this by having statin-users do supervised exercise for 6 weeks, measuring the cardiorespiratory fitness before/after and correlating this to genetic variations present in the participant.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

HMG-CoA Reductase Inhibitor Toxicity

Interventions

Eligibility

Sex: ALLMin age: 35 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * English-speaking * Adults (aged 35-65 years) * Overweight or obese (body-mass index \[BMI\] 25-43) * Currently taking high-dose atorvastatin (40-80mg once daily) for primary prevention of cardiovascular disease and/or stroke * Sedentary (\<30 minutes of structured exercise weekly) * Willing to participate in supervised exercise three times weekly * Willing to not make intentional changes to their diet during the study period. Exclusion Criteria: * Tobacco smokers * Pregnant or breastfeeding * Use other medications that affect lipid metabolism (e.g. fibric acid, fish oil) * Markedly functional debilitated and unable to exert 4 metabolic equivalents (METs) of energy (e.g. unable to climb a flight of stairs without stopping), or who have * Been advised by a physician to avoid exercise due to comorbid serious cardiovascular disease * Uncontrolled diabetes (A1c \> 8) * Uncontrolled thyroid disease * HIV/AIDS * Cancer * History of myocardial infarction or stroke * History of statin-induced myopathy.

Outcomes

Primary Outcomes

Peak oxygen consumption (VO2max)

Change pre/post intervention; compared with genomic variants

Time frame: 6 weeks

Secondary Outcomes

Resting heart rate

Time frame: 6 weeks

Resting systolic blood pressure

Time frame: 6 weeks

Weight

Time frame: 6 weeks

Pharmacogenomic Modulators of Impaired Exercise Adaptation in Statin Users

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes