Biological Effects of Weight Loss In Older, Obese Women

NCT ID: NCT01032733

Last Updated: 2012-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2009-10-31

Brief Summary

Obesity and sedentary lifestyle are associated with physical impairments and biological changes in older adults. Weight loss combined with exercise may reduce inflammation and may improve physical functioning in older adults who are overweight or obese and sedentary. However, the mechanisms by which weight change and exercise influence physical functioning and sarcopenia remain largely understudied. ions). In the WL+E group, participants attended a group-based weight management session plus three supervised exercise sessions each week throughout the entire study. During each exercise session, participants engaged in both aerobic activities (i.e., walking) and lower body resistance training of moderate intensity. The participants in the educational control group attended monthly health education lectures on topics relevant to older adults. It was hypothesized that participants assigned to the WL+E intervention would 1) lose a larger amount of weight, 2) improve their physical function levels, and 3) reduce levels of oxidative stress and inflammation to a greater degree than participants assigned to the Educational Control group. Outcomes are: 1) body weight, 2) walking speed (assessed by 400 meter walk test), 3) the Short Physical Performance Battery [SPPB], and 4) knee extension isokinetic strength. The objectives of this pilot study are fourfold: 1) to demonstrate the feasibility, acceptability, and efficacy of the proposed WL+E intervention in a sample of 40 sedentary, obese older adults with impaired physical functioning; 2) to examine the biological effects of the intervention on inflammatory processes, oxidative stress, apoptosis, sarcopenia, muscle and body composition, muscle strength, and functional performance; 3) to determine whether the expected beneficial effects of the WL+E intervention on physical functioning are mediated by changes in inflammation, apoptosis, and sarcopenia; and 4) to determine the effect size of the WL+E intervention on key outcomes and provide the basis for sample size calculations in the planning of a larger RCT.

Detailed Description

SPECIFIC AIMS A.1. Overview Obesity is associated with a higher level of inflammation and oxidative stress, which in turn are important mediators of sarcopenia, declines in physical functioning, and physical limitations in older adults. Several observational studies and randomized controlled trials (RCTs) suggest that behavioral interventions targeting weight loss through caloric restriction plus exercise (CR +EX) may reduce inflammation and may improve function in obese older adults.3 The mechanisms by which CR +EX may influence physical functioning and sarcopenia (the involuntary loss of skeletal muscle with age) remain largely understudied. It is proposed that CR +EX may avert sarcopenia by reducing inflammation, oxidative damage, and consequent apoptosis of skeletal muscle myocytes.

A.2. Objective of the Pilot Study

The proposed pilot study will lay the groundwork for a RCT of the effects of CR +EX on inflammation, oxidative stress, apoptosis, body composition, intramuscular fat, sarcopenia, muscle strength, and physical functioning in obese older adults. The specific objectives of the proposed study are as follows:

1. Demonstrate the feasibility, acceptability, and efficacy of the proposed intervention, including:

1. Ability to recruit 40 sedentary, older obese adults with mild to moderate functional disability;

2. High rate of attendance at treatment sessions (Mean > 75%); and

3. Good response to treatment (Mean body weight loss > 7%).

2. Evaluate the biological effects of the CR +EX intervention, including changes in:

1. Inflammation (i.e., tumor necrosis factor-α [TNF- α], interleukin-6 [IL-6], myeloperoxidase [MPO]);

2. Oxidative stress (RNA and DNA oxidative damage in leucocytes)

3. Apoptosis (as assessed by caspases and nuclear DNA fragmentation);

4. Body composition (as assessed by dual x-ray absorptiometry [DXA)] and

5. Sarcopenia and muscle composition (i.e., fat free muscle and intramuscular fat, as assessed by Magnetic Resonance Imaging [MRI] and Magnetic Resonance Spectroscopy [MRS]).

3. Examine functional changes associated with weight loss including:

1. Upper and lower extremity muscle strength (as measured by grip strength and isometric and isokinetic ankle and knee strength);

2. Response to the Short Physical Performance Battery; and

3. Self-reported disability.

4. Test whether the expected beneficial effects of the CR +EX intervention on physical functioning are mediated by changes in inflammation, oxidative stress, apoptosis, and sarcopenia;

5. Determine the effect size of the CR +EX intervention on the key outcomes so as to provide the basis for sample size calculations for the planning of the larger RCT.

A.3. Research Hypotheses for the Future RCT

The synergistic effects of CR +EX may be effective in reversing the effects of inflammation, oxidative distress, apoptosis, and sarcopenia on both muscle strength and physical functioning in older adults. Thus, the primary goal of this pilot study is to provide support for a future RCT to test the hypothesis that a lifestyle intervention targeting a 7% loss in body weight through CR + EX will produce greater reductions in these outcomes, as compared to a (no weight loss) control condition. The future RCT would be designed to test the following primary and secondary hypotheses:

Primary hypotheses. As compared with a control condition, the CR +EX Intervention will:

1. Decrease inflammation (as measured by TNF-α, IL-6, and MPO);

2. Decrease oxidative stress (as measured by DNA and RNA damage in isolated leucocytes);

3. Decrease the rate of apoptosis (as measured by caspases and DNA laddering);

4. Produce favorable changes in body composition (i.e., a decrease in total fat mass and an increase in appendicular lean mass, as assessed by DXA); and

5. Produce favorable changes in muscle composition (i.e., a decrease in intramuscular fat and an increase in fat-free muscle as assessed by MRI/MRS).

6. Increase muscle strength and performance (as assessed through validated strength measures)

Conditions

Obesity; Sarcopenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Lifestyle Counseling

In the experimental condition, participants attended a group-based weight management session plus three supervised exercise sessions each week.

Group Type: EXPERIMENTAL

Lifestyle Counseling

Intervention Type: BEHAVIORAL

In the WL+E group, participants attended a group-based weight management session plus three supervised exercise sessions each week.

Educational Control

Participants in the educational control group attended monthly health education lectures on topics unrelated to weight loss.

Group Type: PLACEBO_COMPARATOR

Educational Control

Intervention Type: OTHER

Participants in the educational control group attended monthly health education lectures on topics unrelated to weight loss (e.g., skin protection).

Interventions

Lifestyle Counseling

In the WL+E group, participants attended a group-based weight management session plus three supervised exercise sessions each week.

Intervention Type: BEHAVIORAL

Educational Control

Participants in the educational control group attended monthly health education lectures on topics unrelated to weight loss (e.g., skin protection).

Intervention Type: OTHER

Other Intervention Names

Weight Loss plus Exercise Intervention; Health Educational Group

Eligibility Criteria

Inclusion Criteria

• African American or Caucasian Female
• Age between 55 - 79 years
• BMI > 28 kg/m2
• sedentary lifestyle (defined as < 20 min/week of aerobic exercise)
• mild to moderate physical impairments (score on the Short Physical
• Performance Battery between 4 - 10).

Exclusion Criteria

• Weight >300 lbs.
• Weight loss > 10 lbs. within the past 6 months
• History of surgery for weight loss
• Hospitalization with the past 6 months
• Significant underlying disease likely to limit lifespan and/or increase risk of interventions (cancer or any condition with a life expectancy < 5 years with the exception of non-melanoma skin cancer; serious infectious diseases; myocardia infarction, cerebrovascular accident, or unstable angina within the past 6 months; NYHA Class 3 or 4 congestive heart failure; aortic stenosis; chronic hepatitis; cirrhosis; kidney disease; solid organ transplantation; chronic gastrointestinal disorders; fibromyalgia; chronic fatigue syndrome; major psychiatric disorder).
• Metabolic exclusions (resting blood pressure > 160/90 mmHg, fasting blood glucose > 160 mg/dl, fasting triglycerides > 400 mg/dl; patients on medication for hypertension, diabetes, or hyperlipidemia will not be excluded unless their values suggest "poor control").
• Medication exclusions (Antipsychotic agents; monoamine oxidase inhibitors; systemic corticosteroids; antibiotics for HIV or TB; chemotherapeutic drugs; or current use of prescription weight-loss drugs).
• Physical limitations likely to prevent exercise participation (use of walker; breathing problems that limit physical activity).
• Conditions or behaviors likely to affect the conduct of the trial (e.g., unwilling or unable to give informed consent; unwilling to accept random assignment; likely to move out of area within next 2 years; unable to attend weekly meetings; unwilling to complete paperwork; participation in another randomized research project; unwilling or unable to comply with study requirements or schedule)
• Contraindications to MRI (MR-incompatible implants or severe claustrophobia).
• Contraindications to muscle biopsy (i.e., lidocaine allergy)
• Presence of any other medical condition, which in the opinion of the research staff, would be incompatible with participation in the weight loss plus exercise program.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen D Anton, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Gainesville, Florida, United States

Countries

United States

References

Anton SD, Manini TM, Milsom VA, Dubyak P, Cesari M, Cheng J, Daniels MJ, Marsiske M, Pahor M, Leeuwenburgh C, Perri MG. Effects of a weight loss plus exercise program on physical function in overweight, older women: a randomized controlled trial. Clin Interv Aging. 2011;6:141-9. doi: 10.2147/CIA.S17001. Epub 2011 Jun 15.

Reference Type: RESULT

PMID: 21753869 (View on PubMed)

Wohlgemuth SE, Lees HA, Marzetti E, Manini TM, Aranda JM, Daniels MJ, Pahor M, Perri MG, Leeuwenburgh C, Anton SD. An exploratory analysis of the effects of a weight loss plus exercise program on cellular quality control mechanisms in older overweight women. Rejuvenation Res. 2011 Jun;14(3):315-24. doi: 10.1089/rej.2010.1132. Epub 2011 Jun 1.

Reference Type: RESULT

PMID: 21631380 (View on PubMed)

Other Identifiers

P30AG028740

Identifier Type: NIH

Identifier Source: secondary_id

View Link

3992006

Identifier Type: -

Identifier Source: org_study_id