Fatigability of Lower Limb Muscle in Older Adults: Protective Effects of Strength Training Exercise in Old Men and Women

NCT03888040 | Recruiting DMC

• 2 other identifiers: HR-2945R01AG048262
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed studies will assess 1) the mechanisms for the age-related increase in fatigability during dynamic exercise (Aims 1 and 2) and 2) the effectiveness of high-velocity resistance training coupled with blood flow restriction (BFR) in improving muscle power output and fatigability in older adults (Aim 3). The first two aims are cross-sectional studies comparing young (18-35 years old) and older adults (≥60 yrs old) to test our central hypothesis that the greater accumulation of metabolites and increase in fatigability in older adults is due to either age-related impairments in skeletal muscle bioenergetics (Aim 1) and/or vascular dysfunction (Aim 2). These two aims will integrate techniques to assess whole-muscle bioenergetics (31P-MRS) and in vivo vascular function (near infrared spectroscopy; NIRS and doppler ultrasonography) with in vitro assessment of single fiber bioenergetics (epifluorescence microscopy) and vasoreactivity of isolated skeletal muscle arterioles (video microscopy). We will then determine whether bioenergetics, vascular function and fatigability are altered in older men and women in response to 8 weeks of resistance exercise training of the lower limb both with and without blood flow restriction (Aim 3).

Conditions

Aging

Keywords

Aging; Fatigue; Resistance training; Skeletal Muscle; Knee extensor muscles; limb power

Outcome Measures

Primary Outcomes (8)

• Change in Fatigability of the knee extensor muscles from baseline to after 8 weeks training

  Fatigability will be quantified as the change in limb muscle power output from the start ot the end of a 4-minute dynamic fatiguing exercise.

  One session before and then after 8 weeks of training

• Change in single muscle fiber function form baseline to after 8 weeks training

  Muscle Biopsies: An area of vastus lateralis will numbed by injection with local anesthetic. A small 1/4 inch incision will be made in the skin and a needle inserted briefly into the muscle to remove a piece of muscle about the size of a pencil eraser. The incision is pulled closed with a bandage and the area over the incision will be covered with an elastic pressure bandage. The whole muscle biopsy procedure will take a total of approximately 15 minutes, with the actual biopsy lasting only a few seconds. The biopsy samples will be stored for analyses and used to examine various aspects of skeletal muscle health.

  Before and after completion of resistance training intervention of 8 weeks.

• Change in muscle volume of the quadricep muscles form baseline to after 8 weeks training

  Magnetic resonance imaging (MRI) is used to detect the muscle volume.

  Before and after completion of resistance training intervention of 8 weeks.

• Change in muscle metabolism during a fatiguing knee extensor exercise from baseline to after 8 weeks resistance training

  Phosphorus magnetic resonance spectroscopy (P-MRS) is used to noninvasively measure or calculate a measure of muscle metabolism using intracellular pH in the quadriceps.

  Before and 2-days after completion of resistance training intervention of 8 weeks.

• Change in vascular function via flow-mediated dilation of the femoral artery from baseline to after 8 weeks of training

  Macrovascular endothelial function of the leg with doppler ultrasonography by measuring the blood flow response (velocity and arterial diameter) of the femoral artery after 5 minutes of lower limb occlusion

  One session before and one after 8 weeks of training

• Change in myofibrillar-ATPase efficiency from baseline to after 8 weeks of training

  Myofibrillar ATPase efficiency will be measured during shortening contractions in single fibers isolated from biopsies of the vastus lateralis via epifluorescence microscopy

  One session before and after 8 weeks of training

• Change in Oxygenation of the muscle between baseline to after 8 weeks of training

  Tissue oxygenation levels of the knee extensors muscles will be measured during the 4-minute dynamic fatiguing exercise with near infrared spectroscopy

  One session before and after 8 weeks of training

• Change in arteriole Vasodilation from baseline to after 8 weeks of training

  Acetylcholine-induced vasodilation will be measured in arterioles excised from muscle biopsies of the vastus lateralis via video microscopy

  One session before and after 8 weeks of training

Secondary Outcomes (1)

• Strength

  One session before and after 8 weeks of training

Study Arms (2)

Blood Flow Restriction Training

EXPERIMENTAL

This leg will then perform low-load resistance training (30% of 1-RM) including 3 sets of 15 knee extensions performed as fast as possible while seated upright in a knee extension weight machine. Sets will be interspersed with 30 seconds rest. This leg will always perform the training with blood flow restriction.

Other: Exercise

Resistance Training Only

EXPERIMENTAL

This leg will then perform low-load resistance training (30% of 1-RM) including 3 sets of 15 knee extensions performed as fast as possible while seated upright in a knee extension weight machine. Sets will be interspersed with 30 seconds rest. This leg will always perform the training without blood flow restriction.

Other: Exercise

Interventions

Exercise OTHER

The participant will attend 3 training sessions per week for 8 weeks. Resistance training will be performed by each leg with a load of 30% of maximal strength: one leg with and the other without blood flow restriction.

Blood Flow Restriction Training; Resistance Training Only

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• men and women aged 18-40 years and \>60 years

You may not qualify if:

• body mass index ≥40 kg/m2;
• type 1 or type 2 diabetes;
• uncontrolled hypertension;
• active cancer, cancer in remission, or having received treatment for any form of cancer in the previous five years;
• coronary artery disease;
• cardiovascular disease (e.g., PAD, PVD);
• abnormal and untreated thyroid function;
• chronic and/or regular nonsteroidal anti-inflammatory drugs (NSAID) consumption,
• tobacco use (includes smoking);
• any condition that presents a limitation to exercise (e.g., severe arthritis, COPD, neuromuscular disorder, moderate or severe cognitive impairment, Alzheimer's Disease, severe untreated sleep apnea).
• women who are pregnant or likely to be pregnant.

Sponsors & Collaborators

• Marquette University: lead
• National Institute on Aging (NIA): collaborator
• Medical College of Wisconsin: collaborator

Study Sites (1)

Marquette University

Milwaukee, Wisconsin, 53201, United States

RECRUITING

MeSH Terms

Conditions

Fatigue

Interventions

Exercise

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Christopher W Sundberg, PhD

CONTACT

414-288-5607; christopher.sundberg@marquette.edu

Sarah Lessila

CONTACT

slessila@umich.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Exercise Training Intervention: The older adult subjects that were recruited for the cross-sectional studies will then be asked to return to perform 8 weeks of resistance exercise training on each leg. The exercise will involve low-load, high-velocity power training of the knee extensor muscles. One of the legs will be counterbalanced based on strength to either exercise with blood flow restriction (BFR), while the other leg will exercise without BFR. Before and after the 8 weeks of training subjects will undergo the same measurements in the cross-sectional studies to assess fatigability, skeletal muscle bioenergetics and vascular function of each leg.

Study Record Dates

• First Submitted: March 14, 2019
• First Posted: March 25, 2019
• Study Start: September 1, 2020
• Primary Completion: March 31, 2025
• Study Completion: August 31, 2025
• Last Updated: February 11, 2025

Record last verified: 2024-03

Locations

US (1)