Translational Control of Anabolic Resistance in Aging Muscle

This is an interventional study enrolling older individuals aged 60-85y to observe changes during physical inactivity. This study is investigating the relation between short-term physical inactivity and the impact of muscle health and function. The enrollment goal is 8 participants. The study will occur over the course of a month where participants will undergo testing before and after a reduction in physically activity levels. There will be a screening event collecting baseline data, two body composition scans, muscle function and oral glucose tolerance tests and a metabolic study before and after a 2-week period of inactivity. Each metabolic study will entail three-muscle biopsies: one before and 2 after the ingestion of leucine.

Study Overview

• Status: Completed
• Conditions: Physical Inactivity
• Intervention / Treatment: Other: Reduced Physical Activity

Detailed Description

Pre-testing- The baseline evaluation will assess muscle function and strength, and an oral glucose tolerance test. After the baseline visit, participants will be provided with a step activity monitor to track their level of activity. This will provide a baseline of the participant's normal level of physical activity so an accurate level of 75% activity reduction can be determined. A 3-day daily dietary diary will be provided for the participant to self-report prior to the experiment, as well.

Day 1- After the participant completes their normal activity log and dietary diary, they will be asked to return to the research center for a body composition scan and a metabolic study.

The metabolic study will involve blood sampling from an arm vein and muscle biopsies from the thigh before and after a leucine drink.

2-week period of inactivity- After the metabolic study, the participant will return home and maintain a reduced level of activity (75% reduction) for a two-week period. During this time, the participant will receive phone calls from research personnel in order to maintain adherence to the intervention.

Day 14- After the 2-week reduced activity period, the participant will return to the research center to receive a body composition scan and undergo a metabolic study identical to 'Day 1'.

Post-testing- After Day 14, the participant will be asked to return once again to the research center for a oral glucose tolerance test and the exercise lab for muscle function testing.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 60-85 years
• Ability to sign informed consent
• Free-living, prior to admission

Exclusion Criteria:

• Cardiac abnormalities considered exclusionary by the study physician (e.g., Chronic heart Failure, right-to-left shunt)
• Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, diabetes)
• History of kidney disease or failure
• Vascular disease or risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, diabetes, hypercholesterolemia > 250 mg/dl, claudication or evidence of venous or arterial insufficiency upon palpitation of femoral, popliteal and pedal arteries)
• Risk of blood clotting including family history of thrombophilia, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb>18 g/dL) or thrombocytosis (platelets>400x103/mL), and connective tissue diseases (positive lupus anticoagulant), hyperhomocystinemia, deficiencies of factor V Leiden, proteins S and C, and antithrombine III
• Use of anticoagulant therapy (e.g., Coumadin, heparin)
• Elevated systolic pressure >150 or a diastolic blood pressure > 100
• Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
• Implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators)
• Currently on a weight-loss diet or body mass index > 30 kg/m2
• Chronic systemic corticosteroid use (≥ 2 weeks) within 4 weeks of enrollment and for study duration (intra-articular/topical/inhaled therapeutic or physiologic doses of corticosteroids are permitted). Androgens or growth hormone within 6 months of enrollment and for study duration (topical physiologic androgen replacement is permitted)
• History of stroke with motor disability
• A recent history (<12 months) of GI bleed
• History of liver disease
• History of respiratory disease (acute upper respiratory infection, history of chronic lung disease)
• Prior history of Heparin-Induced Thrombocytopenia
• An HbA1c value at or greater than 6.5%
• Any other condition or event considered exclusionary by the PI and faculty physician

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reduced Physical Activity; Participants will reduce their physical activity levels for 2-weeks by approximately 75% of their baseline level of physical activity	Other: Reduced Physical Activity; Participants will reduce their level of physical activity for 2-weeks as defined as approximately 75% reduction from their baseline level of physical activity.; Other Names: Muscle Disuse

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lean Mass	Change in lean mass	baseline and 2-weeks
Strength	Change in muscle strength	baseline and 2-weeks

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2019
• Primary Completion (Actual): December 17, 2019
• Study Completion (Actual): December 17, 2019

Study Registration Dates

• First Submitted: February 11, 2019
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): June 22, 2022
• Last Update Submitted That Met QC Criteria: June 17, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: Leucine study; R21AR073422 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan has been put into place

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No