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Trial record 63 of 215 for:    Inflammatory Myopathies

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

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ClinicalTrials.gov Identifier: NCT03743675
Recruitment Status : Recruiting
First Posted : November 16, 2018
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Miami University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Overweight and Obesity Inflammation; Muscle Sedentary Lifestyle Behavioral: Diet-Induced Weight Loss Behavioral: Aerobic Exercise Training Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Influence of Aerobic Training and Weight Loss on Skeletal Muscle Inflammatory Markers
Actual Study Start Date : January 31, 2018
Estimated Primary Completion Date : July 30, 2021
Estimated Study Completion Date : September 30, 2021


Arm Intervention/treatment
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.



Primary Outcome Measures :
  1. 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.

  2. 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.



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Ages Eligible for Study:   58 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03743675


Contacts
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Contact: Kyle L Timmerman, PhD 513-529-2930 timmerkl@miamioh.edu
Contact: Mary E Miller, PhD 513-529-2700 mille736@miamioh.edu

Locations
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United States, Ohio
Miami University, Department of Kinesiology and Health, Phillips Hall Recruiting
Oxford, Ohio, United States, 45056
Contact: Anita Sackenheim    513-529-2700    sackenac@miamioh.edu   
Sponsors and Collaborators
Miami University

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Responsible Party: Miami University
ClinicalTrials.gov Identifier: NCT03743675     History of Changes
Other Study ID Numbers: #01488r
First Posted: November 16, 2018    Key Record Dates
Last Update Posted: November 16, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The investigators have no plans to make individual participant data available to researchers outside of their team.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Miami University:
Overweight
Exercise Training
Older Adults
Weight Loss

Additional relevant MeSH terms:
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Myositis
Muscular Diseases
Inflammation
Overweight
Weight Loss
Pathologic Processes
Body Weight
Signs and Symptoms
Body Weight Changes
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases