Nutritional and Contractile Regulation of Muscle Growth

May 1, 2017 updated by: The University of Texas Medical Branch, Galveston

Nutritional and Contractile Regulation of Muscle Growth (Cycle 2)

Muscle wasting, which involves the loss of muscle tissue, is common in many conditions, such as cancer, AIDS, trauma, kidney failure, bone fracture, and sepsis. It is also prevalent among the elderly and in people who experience periods of physical inactivity and weightlessness. Muscle wasting can lead to overall weakness, immobility, physical dependence, and a greater risk of death when exposed to infection, surgery, or trauma. There is a need to develop scientifically based treatments that prevent muscle wasting. As one step towards such a goal, this study will examine the physiological and cellular mechanisms that regulate skeletal muscle growth.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Skeletal muscle comprises about 40% of one's body weight and contains about 50% to 75% of all the proteins in the human body. The turnover of protein is a regular process in the human body. In healthy adults, the interplay between muscle protein synthesis and muscle protein breakdown results in no net growth or loss of muscle mass. But when the scale tips towards muscle protein breakdown, muscle wasting can occur. This can result in negative consequences, because not only does muscle fill the obvious role of converting chemical energy into mechanical energy for moving and maintaining posture, but muscle is also involved in the following less apparent roles: regulating metabolism; removing potentially toxic substances from blood circulation; producing fuel for other tissues; storing energy and nitrogen, both of which are important for fueling the brain and immune system; and facilitating wound healing during malnutrition, starvation, injury, and disease. Therefore, muscle is important not only for physical independence but also for mere survival of the human body. In fact, a mere 30% loss of the body's proteins results in impaired respiration and circulation and can eventually lead to death. The purpose of this study is to examine the physiological and cellular mechanisms that regulate skeletal muscle growth. Results from the study may help to develop future treatments for maintaining and possibly increasing muscle mass as a way to improve function, reduce disease complications, and increase survival.

This study will enroll healthy participants who will be randomly assigned to one of several treatment arms within one of three separate experiments. Overall, the three experiments will examine the following: (1) whether the mammalian target of rapamycin (mTOR) signaling pathway--a group of molecules that work together to control a specific cellular function--is responsible for stimulating muscle protein synthesis after resistance exercise and/or ingestion of an amino acid supplement; (2) whether restricting blood flow with a blood pressure cuff during low-intensity resistance exercise ultimately leads to muscle protein synthesis; and (3) whether aging is associated with reduced physiological and cellular mechanisms that are related to muscle protein synthesis and whether such a reduction can be overcome by post-exercise ingestion of an amino acid supplement or blood flow restriction during low-intensity resistance exercise.

Depending on which treatment arm participants are assigned to, they may receive amino acid supplementation, the drug rapamycin, the drug sodium nitroprusside, and/or placebo. They may also undergo high-intensity resistance exercise, low-intensity resistance exercise, or low-intensity resistance exercise along with blood flow restriction. All participants will attend a single 8-hour study visit and a follow-up visit 1 week later. During the study visit, participants will undergo the following: measurements of vital signs, height, and weight; blood and urine sampling; a dual energy x-ray absorptiometry (DEXA) scan; and an infusion study that will include additional blood sampling, muscle biopsies, and assigned interventions. The follow-up visit will include evaluation of any incisions that were made during the infusion study.

Study Type

Interventional

Enrollment (Actual)

144

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Galveston, Texas, United States, 77550
        • Department of Nutrition & Metabolism, University of Texas Medical Branch

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18 to 35 years of age for the young groups
  • 60 to 85 years of age for the older groups
  • In the follicular phase for the young women participants
  • Ability to sign consent form, as based on a score of greater than 25 on the 30-item Mini Mental State Examination (MMSE)
  • Stable body weight for at least 1 year

Exclusion Criteria:

  • Physical dependence or frailty, as determined by impairment in any of the activities of daily living (ADLs), history of more than two falls per year, or significant weight loss in the past year
  • Exercise training that consists of more than two weekly sessions of moderate to high intensity aerobic or resistance exercise
  • Significant heart, liver, kidney, blood, or respiratory disease
  • Peripheral vascular disease
  • Diabetes mellitus or other untreated endocrine disease
  • Active cancer
  • History of cancer for participants who may be randomly assigned to rapamycin)
  • Acute infectious disease or history of chronic infections (e.g., tuberculosis, hepatitis, HIV, herpes)
  • Treatment with anabolic steroids or corticosteroids within 6 months of study entry
  • Alcohol or drug abuse
  • Tobacco use (smoking or chewing)
  • Malnutrition (e.g., body mass index [BMI] less than 20 kg/m2, hypoalbuminemia, and/or hypotransferrinemia)
  • Obesity (BMI greater than 30 kg/m2)
  • Lower than normal hemoglobin levels

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Exp 1: AA + Rap
Participants will receive amino acid supplementation and rapamycin.
Drug: Rapamycin
Single 16-mg oral dose
Other: Amino acid supplementation
Nutritional drink containing essential amino acids
Placebo Comparator: Exp 1: AA
Participants will receive amino acid supplementation and placebo rapamycin.
Other: Amino acid supplementation
Nutritional drink containing essential amino acids
Active Comparator: Exp 1: HEx + Rap
Participants will receive rapamycin and placebo amino acid supplementation, and they will undergo high-intensity resistance exercise.
Drug: Rapamycin
Single 16-mg oral dose
Other: Low-intensity resistance exercise
Leg extension exercises on a Cybex leg extension machine
Placebo Comparator: Exp 1: HEx
Participants will receive placebo amino acid supplementation and placebo rapamycin, and they will undergo high-intensity resistance exercise.
Other: Low-intensity resistance exercise
Leg extension exercises on a Cybex leg extension machine
Active Comparator: Exp 1: HEx + AA + Rap
Participants will receive amino acid supplementation and rapamycin, and they will undergo high-intensity resistance exercise.
Drug: Rapamycin
Single 16-mg oral dose
Other: Amino acid supplementation
Nutritional drink containing essential amino acids
Other: Low-intensity resistance exercise
Leg extension exercises on a Cybex leg extension machine
Placebo Comparator: Exp 1: HEx + AA
Participants will receive amino acid supplementation and placebo rapamycin, and they will undergo high-intensity resistance exercise.
Other: Amino acid supplementation
Nutritional drink containing essential amino acids
Other: Low-intensity resistance exercise
Leg extension exercises on a Cybex leg extension machine
Active Comparator: Exp 2: LExFR + Rap
Participants will receive rapamycin and will undergo low-intensity resistance exercise with blood flow restriction.
Drug: Rapamycin
Single 16-mg oral dose
Other: Low-intensity resistance exercise
Leg extension exercises on a Cybex leg extension machine
Device: Blood flow restriction cuff
Blood flow restriction for 5 minutes after the second biopsy
Other Names:
  • KAATSU cuff
Placebo Comparator: Exp 2 and 3: LExFR
Participants will receive placebo rapamycin and will undergo low-intensity resistance exercise with blood flow restriction.
Other: Low-intensity resistance exercise
Leg extension exercises on a Cybex leg extension machine
Device: Blood flow restriction cuff
Blood flow restriction for 5 minutes after the second biopsy
Other Names:
  • KAATSU cuff
Active Comparator: Exp 2: SNP
Participants will receive sodium nitroprusside in a resting state.
Drug: Sodium nitroprusside
Variable rate for 3 hours
Active Comparator: Exp 2: FR
Participants will undergo blood flow restriction in a resting state.
Device: Blood flow restriction cuff
Blood flow restriction for 5 minutes after the second biopsy
Other Names:
  • KAATSU cuff
Active Comparator: Exp 2: LEx + SNP
Participants will receive sodium nitroprusside and undergo low-intensity resistance exercise.
Other: Low-intensity resistance exercise
Leg extension exercises on a Cybex leg extension machine
Drug: Sodium nitroprusside
Variable rate for 3 hours
Placebo Comparator: Exp 3: LEx
Participants will undergo low-intensity resistance exercise.
Other: Low-intensity resistance exercise
Leg extension exercises on a Cybex leg extension machine
Active Comparator: Exp 3: HEx
Participants will undergo high-intensity resistance exercise.
Other: Low-intensity resistance exercise
Leg extension exercises on a Cybex leg extension machine
Active Comparator: Exp 3: HEx + AA
Participants will receive amino acid supplementation and will undergo high-intensity resistance exercise.
Other: Low-intensity resistance exercise
Leg extension exercises on a Cybex leg extension machine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Muscle protein synthesis
Time Frame: Measured during the 8-hour infusion study
Measured during the 8-hour infusion study

Secondary Outcome Measures

Outcome Measure
Time Frame
Phosphorylation status of mTOR signaling proteins
Time Frame: Measured during the 8-hour infusion study
Measured during the 8-hour infusion study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Texas Medical Branch, Galveston

Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

  • Principal Investigator: Blake Rasmussen, PhD, The University of Texas Medical Branch, Galveston

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

March 1, 2015

Study Registration Dates

First Submitted

April 29, 2009

First Submitted That Met QC Criteria

April 30, 2009

First Posted (Estimate)

May 1, 2009

Study Record Updates

Last Update Posted (Actual)

May 4, 2017

Last Update Submitted That Met QC Criteria

May 1, 2017

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-306
  • R01AR049877 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sarcopenia

Clinical Trials on Rapamycin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Chile

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe