BFR and Muscle Mitochondrial Oxidative Capacity

Study Overview
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Brief Summary
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Blood flow restricted (BFR) exercise has been shown to improve skeletal muscle adaptations to resistance exercise. BFR uses blood pressure cuffs (i.e., tourniquets) to reduce skeletal muscle blood flow during resistance exercise. One benefit of BFR is that skeletal muscle adaptations to resistance exercise training including muscle hypertrophy and increases in strength can be achieved at lower-loads (e.g., 25-30% 1RM), that are often comparable to more traditional resistance training loads (70-85% 1RM). However, the impact that low-load BFR resistance exercise has on muscle quality and bioenergetics is unknown. The present study will examine the impact of 6 weeks of low-load, single-leg resistance exercise training with or without personalized BFR on measures of muscle mass, strength, quality, and mitochondrial bioenergetics. The investigators will recruit and study up to 30, previously sedentary, healthy, college-aged adults (18-40 years). The investigators will measure muscle mass using Dual Energy X-Ray Absorptiometry and muscle strength and endurance using isokinetic testing. The investigators will normalize knee extensor strength to lower limb lean mass to quantify muscle quality. The investigators will also use near infrared spectroscopy (NIRS) to measure mitochondrial oxidative capacity in the vastus lateralis. Finally, the investigators will measure markers of systemic inflammation and markers of muscle damage using commercially available ELISA assays.

Official Title
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Impact of Low-Intensity Resistance Exercise With and Without Blood Flow Redistricted (BFR) on Muscle Mitochondrial Oxidative Capacity

Conditions
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Mitochondria, Strength, Hypertrophy

Intervention / Treatment
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* Behavioral: Low Load Resistance Exercise
* Behavioral: Low Load Resistance Exercise + BFR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria. Capable and willing to give written informed consent Capable of understanding inclusion and exclusion criteria 18-40 years of age inclusive Body Mass Index (BMI) between 18.5-30 kg/m2 inclusive No medical condition that would limit their participation in supervised exercise training based on the Physical Activity Readiness Questionnaire for Everyone (PARQ+) No current prescription medications, with the exception of birth control Willing to allow researchers to use data, biospecimens (e.g., blood) and images (e.g., Dual Energy x-Ray Absorptiometry) for research purposes after study participation is completed Exclusion Criteria. Evidence or self-report being pregnant, lactating, or anticipating becoming pregnant in the next year Participation in resistance or aerobic exercise training > 2 days per week within the 3 months prior to screening Self-report of history of type 1 or 2 diabetes mellitus Self-report history of cardiovascular, peripheral vascular, cerebral vascular, pulmonary, or renal disease Self-report or evidence of uncontrolled hypertension Self-report history of blood clotting disorders Self-report history of deep vein thrombosis or pulmonary embolism Self-report history of sickle cell trait Self-report history of varicose veins Self-report history of a myopathy leading to muscle loss, weakness, severe cramps or myalgia Self-report history of orthopedic limitations that would preclude them from participation in a dynamic exercise program Self-report history of musculoskeletal disorders (e.g., severe osteoarthritis, rheumatoid arthritis, avascular necrosis or osteonecrosis) Self-report history of neurological disorders (e.g., peripheral neuropathy, amyotrophic lateral sclerosis, multiple sclerosis, fibromyalgia, Parkinson's disease) Weight loss of > 10% in the last 3 months prior to screening Active smoking Current consumption of > 14 alcoholic drinks per week based on self-report Absolute Contraindication to Exercise as Defined by the American College of Sports Medicine,1 including: Resting diastolic blood pressure > 100 mm Hg Resting systolic blood pressure > 180 mm Hg Resting heart rate > 100 beats per min Self-report acute viral or bacterial upper or lower respiratory infection at screening Any other condition that in the judgement of the Principal Investigator and/or the Medical Director of this protocol may interfere with study participation and adherence to the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low Load Resistance Exercise<br>Subjects allocated to Low Load Resistance Exercise will undergo 6 weeks of single-legged low load (25%) resistance exercise. Their contralateral leg will serve as within subject control. | Behavioral: Low Load Resistance Exercise<br>* Subjects allocated to Low Load Resistance Exercise will undergo 6 weeks of single-legged low load (25%) resistance exercise. Subjects will then perform 4 sets of 30, 15, 15 and 15 repetitions at 25% of their 1RM for the single-legged leg press and single-legged knee extensions. Their contralateral leg will serve as within subject control.<br>|
| Experimental: Low Load Resistance Exercise + BFR<br>Subjects allocated to Low Load Resistance Exercise + BFR will undergo 6 weeks of single-legged low load (25%) resistance exercise plus blood flow restriction. Their contralateral leg will serve as within subject control. | Behavioral: Low Load Resistance Exercise + BFR<br>* Subjects allocated to Low Load Resistance Exercise + BFR will undergo 6 weeks of single-legged low load (25%) resistance exercise with blood flow restriction (60% occlusion pressure). Subjects will then perform 4 sets of 30, 15, 15 and 15 repetitions at 25% of their 1RM for the single-legged leg press and single-legged knee extensions. Their contralateral leg will serve as within subject control.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Mitochondrial Oxidative Capacity | Changes in mitochondrial oxidative capacity will be measured using near infrared spectroscopy (NIRS). | Changes from baseline (pre-training) to follow-up (about 48-72 hours post-training). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Muscle Mass measured by Dual Energy X-ray Absorptiometry | Changes in muscle mass will be measured by Dual Energy X-ray Absorptiometry | Changes from baseline (pre-training) to follow-up (about 48-72 hours post-training) | 
| Changes in Muscle Strength measured using Isokinetic Dynamometry | Changes in muscle strength measured using isokinetic dynamometry | Changes from baseline (pre-training) to follow-up (about 48-72 hours post-training) | 
| Changes in Muscle Endurance measured using Isokinetic Dynamometry | Changes in muscle endurance measured using isokinetic dynamometry | Changes from baseline (pre-training) to follow-up (about 48-72 hours post-training) |