Overweight and ObesityNCT03743675
Influence of Aerobic Training and Weight Loss on Skeletal Muscle Inflammatory Markers and Muscle Protein Balance in Older Adults
A study testing Diet-Induced Weight Loss and Aerobic Exercise Training in people with Overweight and Obesity and Inflammation; Muscle, run by Miami University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 58 years and olderHealthy volunteers can take part
- Conditions the study is for
- Overweight and Obesity, Inflammation; Muscle, Sedentary Lifestyle
- What is being tested?
- Diet-Induced Weight Loss and Aerobic Exercise Training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2018to 30 Sep 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 58 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- Alcohol or drug abuse
- Prescription anti-coagulant use
- Allergy to lidocaine
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Miami University, Department of Kinesiology and Health, Phillips Hall
Oxford, Ohio, 45056
Anita Sackenheim, 513-529-2700, sackenac@miamioh.edu
About this study
Official title: 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.
- Being tested
- Diet-Induced Weight Loss, Aerobic Exercise Training
- Keywords
- Overweight, Exercise Training, Older Adults, Weight Loss
- Medical subject headings
- Overweight, Obesity, Myositis, Inclusion Body, Sedentary Behavior, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diet-Induced Weight LossBehavioural
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.
Aerobic Exercise TrainingBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Diet-Induced Weight Loss | Experimental | Subjects in this arm will undergo 6-months of dietary counseling targeting 5-10% weight loss by the end of the intervention period. Receives: Behavioral: Diet-Induced Weight Loss |
| Exercise Training | Experimental | Subjects in this arm will undergo 6-months of supervised aerobic exercise training (3 days per week, moderate-to-vigorous intensity). Receives: Behavioral: Aerobic Exercise Training |
| Diet Plus Exercise | Experimental | 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). Receives: Behavioral: Diet-Induced Weight Loss; Behavioral: Aerobic Exercise Training |
| Control | No intervention | 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 being measured
The primary outcome is the main question the study is designed to answer.
Skeletal Muscle Inflammation
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.
Measured: 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
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.
Measured: Change from baseline nutrient-stimulated mTOR and S6K1 activation at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2018
- Study start31 Jan 2018
- Primary completion30 Jul 2021 (estimated)
- Study completion30 Sep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Overweight and ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Miami University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03743675
- Sponsor's protocol ID
- #01488r
- Status last verified
- Oct 2018
- First submitted
- 18 Oct 2018
- Last updated
- 16 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The investigators have no plans to make individual participant data available to researchers outside of their team.
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Aerobic Training and Weight Loss on Skeletal Muscle Inflammatory Markers
- ClinicalTrials.gov ID
- NCT03743675
- Acronym / sponsor ID
- #01488r
- Keywords
- Overweight, Exercise Training, Older Adults, Weight Loss
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Miami UniversityUniversity, hospital or other
- Study start
- 31 Jan 2018 (actual)
- Primary completion
- 30 Jul 2021 (estimated)
- Study completion
- 30 Sep 2021 (estimated)
- First posted
- 16 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Diet-Induced Weight Loss | Experimental | Behavioral: Diet-Induced Weight LossSubjects in this arm will undergo 6-months of dietary counseling targeting 5-10% weight loss by the end of the intervention period. |
| Exercise Training | Experimental | Behavioral: Aerobic Exercise TrainingSubjects in this arm will undergo 6-months of supervised aerobic exercise training (3 days per week, moderate-to-vigorous intensity). |
| Diet Plus Exercise | Experimental | Behavioral: Diet-Induced Weight Loss, Behavioral: Aerobic Exercise TrainingSubjects 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). |
| Control | No intervention | –Subjects in this group will be asked to maintain their habitual physical activity, and will received counseling regarding a healthy, weight-maintenance diet. |
Who may qualify
- Ages
- 58 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- Physical dependence
- History of falls (≥ 2/yr)
- Significant cardiovascular, metabolic, or pulmonary disease
- Implantable defibrillator or pacemaker
- Active cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Diet-Induced Weight LossDiet-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. | Behavioural | Diet Plus Exercise, Diet-Induced Weight Loss |
| Aerobic Exercise TrainingExercise 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. | Behavioural | Diet Plus Exercise, Exercise Training |
Primary outcome
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.
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2018.
- Individual participant dataSharing planned: No. The investigators have no plans to make individual participant data available to researchers outside of their team.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Diet-Induced Weight Loss and Aerobic Exercise Training in people with Overweight and Obesity and Inflammation; Muscle, run by Miami University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kyle L Timmerman, PhD (513-529-2930, timmerkl@miamioh.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Skeletal Muscle Inflammation (time frame: Change from baseline TACE and TNFa expression at 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2018.