Biological Effects of Weight Loss In Older, Obese Women
Condition: Obesity; Sarcopenia
MeSH terms: Sarcopenia; Weight Loss
Study type: Interventional
Phase: Phase 2

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)
    

Intervention name(s): Lifestyle Counseling; Educational Control
Intervention type(s): Behavioral; Other
Intervention description(s): In the WL+E group, participants attended a group-based weight management session plus three supervised exercise sessions each week.; Participants in the educational control group attended monthly health education lectures on topics unrelated to weight loss (e.g., skin protection).
Other intervention name(s): Weight Loss plus Exercise Intervention; Health Educational Group
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Weight Loss; Physical Function; Oxidative Stress; Inflammation