Clinical trial NCT03888040: Fatigability of Lower Limb Muscle in Older Adults: Protective Effects of Strength Training Exercise in Old Men and Women
Official title: Fatigability of Limb Muscle in Older Adults: Protective Effects of Exercise
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aging
Keywords: Aging
Fatigue
Resistance training
Skeletal Muscle
Knee extensor muscles
limb power
Lead sponsor: Marquette University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: Medical College of Wisconsin
First posted: 2019-03-25
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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.
* Subjects will be excluded if they have joint pain in the exercising leg or arm. Medication use. Medications currently taken or in the previous year and known to influence muscle mass (e.g., glucocorticoids, testosterone) and cortical and neuromuscular excitability will be exclusionary, while medications that may be prevalent among older adults (e.g., statins) will be accounted for with a covariate statistical model.

Primary outcomes:
measure: Change in Fatigability of the knee extensor muscles from baseline to after 8 weeks training
timeFrame: One session before and then after 8 weeks of training
measure: Change in single muscle fiber function form baseline to after 8 weeks training
timeFrame: Before and after completion of resistance training intervention of 8 weeks.
measure: Change in muscle volume of the quadricep muscles form baseline to after 8 weeks training
timeFrame: Before and after completion of resistance training intervention of 8 weeks.
measure: Change in muscle metabolism during a fatiguing knee extensor exercise from baseline to after 8 weeks resistance training
timeFrame: Before and 2-days after completion of resistance training intervention of 8 weeks.
measure: Change in vascular function via flow-mediated dilation of the femoral artery from baseline to after 8 weeks of training
timeFrame: One session before and one after 8 weeks of training
measure: Change in myofibrillar-ATPase efficiency from baseline to after 8 weeks of training
timeFrame: One session before and after 8 weeks of training
measure: Change in Oxygenation of the muscle between baseline to after 8 weeks of training
timeFrame: One session before and after 8 weeks of training
measure: Change in arteriole Vasodilation from baseline to after 8 weeks of training
timeFrame: One session before and after 8 weeks of training
Secondary outcomes:
measure: Strength
timeFrame: One session before and after 8 weeks of training
Other outcomes:
Locations:
city: Milwaukee
country: United States
facility: Marquette University
state: Wisconsin
Study officials:
References: