Nutritional and Contractile Regulation of Muscle Growth

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by The University of Texas, Galveston
Sponsor:
Collaborator:
Information provided by (Responsible Party):
The University of Texas, Galveston
ClinicalTrials.gov Identifier:
NCT00891696
First received: April 29, 2009
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention
Sarcopenia
Drug: Rapamycin
Other: Amino acid supplementation
Other: Low-intensity resistance exercise
Drug: Sodium nitroprusside
Device: Blood flow restriction cuff

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Nutritional and Contractile Regulation of Muscle Growth (Cycle 2)

Resource links provided by NLM:


Further study details as provided by The University of Texas, Galveston:

Primary Outcome Measures:
  • Muscle protein synthesis [ Time Frame: Measured during the 8-hour infusion study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phosphorylation status of mTOR signaling proteins [ Time Frame: Measured during the 8-hour infusion study ] [ Designated as safety issue: No ]

Estimated Enrollment: 144
Study Start Date: April 2009
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Device: Blood flow restriction cuff
Blood flow restriction for 5 minutes after the second biopsy
Other Name: KAATSU cuff
Other: Low-intensity resistance exercise
Leg extension exercises on a Cybex leg extension machine
Placebo Comparator: Exp 2 and 3: LExFR
Participants will receive placebo rapamycin and will undergo low-intensity resistance exercise with blood flow restriction.
Device: Blood flow restriction cuff
Blood flow restriction for 5 minutes after the second biopsy
Other Name: KAATSU cuff
Other: Low-intensity resistance exercise
Leg extension exercises on a Cybex leg extension machine
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 Name: KAATSU cuff
Active Comparator: Exp 2: LEx + SNP
Participants will receive sodium nitroprusside and undergo low-intensity resistance exercise.
Drug: Sodium nitroprusside
Variable rate for 3 hours
Other: Low-intensity resistance exercise
Leg extension exercises on a Cybex leg extension machine
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00891696

Contacts
Contact: Blake Rasmussen, PhD 409-747-1619 blrasmus@utmb.edu
Contact: Syed Habeebullah Husaini 214-729-8893 shhusain@utmb.edu

Locations
United States, Texas
Department of Nutrition & Metabolism, University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77550
Principal Investigator: Blake Rasmussen, PhD         
Sponsors and Collaborators
The University of Texas, Galveston
Investigators
Principal Investigator: Blake Rasmussen, PhD The University of Texas Medical Branch, Galveston
  More Information

No publications provided by The University of Texas, Galveston

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: The University of Texas, Galveston
ClinicalTrials.gov Identifier: NCT00891696     History of Changes
Other Study ID Numbers: 08-306, R01AR049877
Study First Received: April 29, 2009
Last Updated: June 5, 2014
Health Authority: United States: Federal Government

Keywords provided by The University of Texas, Galveston:
Sarcopenia
Aging
Metabolism
Muscle
mTOR
Essential Amino Acids
Exercise
Rapamycin

Additional relevant MeSH terms:
Sarcopenia
Muscular Atrophy
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Atrophy
Pathological Conditions, Anatomical
Signs and Symptoms
Sirolimus
Everolimus
Nitroprusside
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antihypertensive Agents
Cardiovascular Agents
Vasodilator Agents
Nitric Oxide Donors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014