Influence of Aerobic Training and Weight Loss on Skeletal Muscle Inflammatory Markers and Muscle Protein Balance in Older Adults

November 13, 2018 updated by: Miami University

Influence of Aerobic Training and Weight Loss on Skeletal Muscle Inflammatory Markers

It is estimated that 15% of adults aged 60-70 years, and up to 50% of adults aged 80 years and older are affected by sarcopenia-the age related loss of muscle mass and function. A disruption of the homeostatic balance between periods of muscle protein breakdown (predominant during fasting) and muscle protein synthesis (predominant following nutrient ingestion) can result in the loss of muscle mass over time. In particular, research suggests that an inability of muscle to fully respond to the anabolic influence of nutrient intake may contribute significantly to age-related muscle loss. This anabolic resistance is likely influenced by increased age-related inflammation. There is evidence in cell line and animal models that increased levels of the inflammatory cytokine, tumor necrosis factor-α (TNFα) impairs the molecular pathways that initiate muscle protein synthesis (i.e. mammalian target of rapamycin, mTOR signaling), and can accelerate muscle protein breakdown. Obesity, and sedentary lifestyle have been linked to increased TNFα expression, and thus may partially explain impaired muscle protein balance in older adults. The objectives of this clinical trial are to 1) determine if lifestyle modification via weight loss and aerobic exercise can reduce skeletal muscle inflammation and subsequently improve nutrient-stimulated muscle protein synthesis in previously sedentary, obese older adults; and 2) expose undergraduate Kinesiology and Nutrition majors to meritorious research. The investigators have recently published data with undergraduate researchers showing that body composition is associated with elevated skeletal muscle expression of TNFα converting enzyme (TACE). One of the primary actions of TACE is to cleave membrane bound TNFα (mTNFα) to soluble TNFα (sTNFα)-a more mature and bioactive form of TNFα. Both TACE and sTNFα are known to be elevated in a number of clinical conditions, including heart disease, cancer, arthritis, and diabetes. Based on these data, the investigators feel that TACE may represent an important and potentially modifiable (via weight loss and aerobic conditioning) regulator of skeletal muscle inflammation in humans. There are currently no data on the associations among skeletal muscle expression of TACE, TNFα, and muscle protein balance. Thus, the focus of this study is to determine if 5-10% diet-induced weight loss and 6-months (3 days per week) of aerobic exercise training can influence: 1) TACE and TNFα expression in skeletal muscle; and 2) improve molecular indices of muscle protein breakdown and nutrient-stimulated muscle protein synthesis (mTOR signaling) in sedentary, obese older adults. Specifically, 60 sedentary, obese older adults will be randomized to one of the following groups: 1) control group (CON), 2) a diet-induced weight loss group (DIET), 3) an aerobic exercise training group (EX), or 4) a diet-induced weight loss + aerobic exercise training group (DIET + EX). The results of this study will advance the understanding of the connections among skeletal muscle inflammation and muscle protein balance in older adults, and validate TACE as a potentially modifiable target for the prevention and treatment of sarcopenia and other age-related inflammatory diseases, which will contribute to the development of practice-based guidelines for healthcare practitioners.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Ohio
      • Oxford, Ohio, United States, 45056
        • Recruiting
        • Miami University, Department of Kinesiology and Health, Phillips Hall
        • Contact:

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

58 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Men and women
  • 58 years or older
  • Sedentary (<500 kcal/wk of physical activity)
  • BMI > 30 kg/m2
  • Stable body weight for at least 1 year
  • Approval from primary care provider

Exclusion Criteria:

  • Physical dependence
  • History of falls (≥ 2/yr)
  • Significant cardiovascular, metabolic, or pulmonary disease
  • Implantable defibrillator or pacemaker
  • Active cancer
  • Recent (within 6 months) treatment with anabolic steroids, or corticosteroids
  • Alcohol or drug abuse
  • Prescription anti-coagulant use
  • Allergy to lidocaine

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
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Diet-Induced Weight Loss
Subjects in this arm will undergo 6-months of dietary counseling targeting 5-10% weight loss by the end of the intervention period.
Behavioral: Diet-Induced Weight Loss
Diet-Induced Weight Loss: The goal of the diet intervention is to produce a weight loss of approximately 5-10% of body weight over the six-month period, which is consistent with the goals for obesity treatment outlined by the Academy of Nutrition and Dietetics (AND). According to the 2016 AND position paper for obesity-related interventions, this level of weight loss produces clinically significant reductions in biometrics (biochemical and anthropometrics measurements) and associated risk factors for chronic disease. Additionally, obese older adults who achieve weight loss intentionally through lifestyle changes experience improved physical function. This intervention will last for 6-months with bi-weekly face-to-face counseling sessions with a registered dietitian.
EXPERIMENTAL: Exercise Training
Subjects in this arm will undergo 6-months of supervised aerobic exercise training (3 days per week, moderate-to-vigorous intensity).
Behavioral: Aerobic Exercise Training
Exercise Intervention: Subjects will exercise on a cycle ergometer during the training sessions. Each session will consist of 1) a 5-10 minute warm up at "light" intensity; 2) a 20 to 30-minute training phase at "moderate-to-vigorous" intensity; and 3) a 5-minute cool down phase at "light". The training will be conducted 3 days per week for 6 months.
EXPERIMENTAL: Diet Plus Exercise
Subjects in this arm will undergo 6-months of dietary counseling targeting 5-10% weight loss by the end of the intervention period. They will simultaneously undergo 6-months of supervised aerobic exercise training (3 days per week, moderate-to-vigorous intensity).
Behavioral: Diet-Induced Weight Loss
Diet-Induced Weight Loss: The goal of the diet intervention is to produce a weight loss of approximately 5-10% of body weight over the six-month period, which is consistent with the goals for obesity treatment outlined by the Academy of Nutrition and Dietetics (AND). According to the 2016 AND position paper for obesity-related interventions, this level of weight loss produces clinically significant reductions in biometrics (biochemical and anthropometrics measurements) and associated risk factors for chronic disease. Additionally, obese older adults who achieve weight loss intentionally through lifestyle changes experience improved physical function. This intervention will last for 6-months with bi-weekly face-to-face counseling sessions with a registered dietitian.
Behavioral: Aerobic Exercise Training
Exercise Intervention: Subjects will exercise on a cycle ergometer during the training sessions. Each session will consist of 1) a 5-10 minute warm up at "light" intensity; 2) a 20 to 30-minute training phase at "moderate-to-vigorous" intensity; and 3) a 5-minute cool down phase at "light". The training will be conducted 3 days per week for 6 months.
NO_INTERVENTION: Control
Subjects in this group will be asked to maintain their habitual physical activity, and will received counseling regarding a healthy, weight-maintenance diet.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Skeletal Muscle Inflammation
Time Frame: Change from baseline TACE and TNFa expression at 6 months
Skeletal muscle biopsies will be taken at baseline and following 6-months of the interventions to assess changes in indices of inflammation including tumor necrosis factor-alpha (TNFa) and TNFa converting enzyme (TACE). Analyses will be made utilizing Western blots, along with appropriate loading and positive controls. Outcome data will be normalized to an internal loading control and presented as arbitrary units.
Change from baseline TACE and TNFa expression at 6 months
The activation of mammalian target of rapamycin (mTOR) signaling in the fasted and postprandial state
Time Frame: Change from baseline nutrient-stimulated mTOR and S6K1 activation at 6 months
At baseline and following 6-months of the interventions, muscle biopsies will be taken in the fasted state and following ingestion of a beverage containing 0.5 g/kg body mass carbohydrate + 0.3 g/kg body mass protein by the subjects. 60 and 120 minutes after ingestion, biopsies will also be taken. Using Western blot analyses, the total and phosphorylated protein expression of mTOR, as well as its downstream signaling protein, S6K1 will be measured. Data will be expressed as phosphorylated-to-total abundance. This pathway has been shown to be critical for the stimulation of muscle protein synthesis (MPS) in response to nutrient intake. A higher ratio of phosphorylated:total abundance of these proteins (expressed as arbitrary units) indicates increased activation of MPS. It is hypothesized that the fasted-to-postprandial fold-change in activation of these proteins will be greater following 6-months of diet-induced weight loss and/or exercise training compared to a control group.
Change from baseline nutrient-stimulated mTOR and S6K1 activation at 6 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Miami University

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 (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 31, 2018

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 30, 2021

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 18, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 13, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 16, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 16, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 13, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • #01488r

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The investigators have no plans to make individual participant data available to researchers outside of their team.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

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