Obesity, Overweight With Indications for Weight Loss
Conditions
Keywords
Body Composition, Sarcopenia, Weight loss trials, Intervention studies, Elderly
Brief summary
The purpose of this pilot study is to compare two strategies intended to improve the health of overweight older adults by improving body composition. One strategy, resistance training, is designed to preserve skeletal muscle mass. The other strategy, the use of a PPAR-γ agonist, is designed to enhance the loss of fat from visceral and skeletal depots. These strategies will be used in conjunction with a hypocaloric diet and will be compared to a hypocaloric diet alone to determine if either of these strategies are superior in reducing visceral fat and preserving muscle mass.
Detailed description
In this pilot we propose to recruit 88 older (65 - 79 yrs) men (n=48) and women (n=40) at risk for disability and with indications for weight loss according to NIH guidelines. All will be enrolled in a dietary intervention designed to generate a caloric deficit of 500 kcal/day for a 4 month period. All will receive supplemental vitamin D and calcium. These participants will be randomized into one of 4 groups: Group 1 - Hypocaloric diet (and placebo) Group 2 - Hypocaloric diet and resistance training designed to maximize muscular power (and placebo) Group 3 - Hypocaloric diet and a PPAR- γ agonist (pioglitazone/Actos™) Group 4 - Hypocaloric diet and resistance training and pioglitazone/Actos™ The specific aims of the pilot are: 1. In both men and women, to determine whether randomization to resistance exercise is associated with an increased retention of appendicular non-bone lean mass compared to those not undergoing power training. 2. In both men and women, to determine whether randomization to the pioglitazone group is associated with an increased loss of visceral adiposity relative to randomization to the non-pioglitazone group. 3. Assess the feasibility of the recruitment, assessment and intervention strategies 4. To estimate adherence to the weight loss, exercise training, and drug interventions; 5. In this population, to determine measurement characteristics of the functional outcomes that will be considered as primary end-points of the larger study. 6. To obtain pilot data on a subset of participants to determine the feasibility, acceptability and measurement characteristics of muscle samples (biopsies) to quantify intramyocellular lipid in this study population.
Interventions
DRUGPioglitazone
BEHAVIORALResistance exercise training to maximize muscle power
BEHAVIORALHypocaloric diet
DRUGPlacebo
Sponsors
Takeda Pharmaceuticals North America, Inc.
National Institute on Aging (NIA)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
65 Years to 79 Years
Healthy volunteers
Yes
Inclusion criteria
* Weight Stable, Indication for weight loss per NIH guidelines, Performance on the short physical performance battery score 3-10
Exclusion criteria
* Diabetes, weight \> 136 kg, Medical condition that limits exercise participation, Congestive heart failure, abnormal kidney function, higher ALT than normal, currently involved in a weight loss or exercise program, current smoking, alcohol or drug abuse, taking anti-inflammatory steroids, taking protein supplements, taking PPAR-gamma agonist, edema, anemia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Appendicular Non-bone Lean Mass | Baseline visit (pre intervention) and 4month follow up (post intervention) | Change in Appendicular Non-bone Lean Mass |
Secondary
| Measure | Time frame |
|---|---|
| Lean Body Mass | Baseline visit (pre intervention) and 4month follow up (post intervention) |
Countries
United States
Participant flow
Recruitment details
Starting in April 2006,144 participants underwent a medical screening. After further exclusion (n = 47) and declining to participate (n = 9), 88 participants (48 men, 40 women) were randomized to one of the four treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Hypocaloric Weight Loss Only Two meal replacements per day (bars and shakes) were provided to all participants (containing \
220 kcal with 7-10 g protein, 33-46 g carbohydrates, and 1.5-5 g fat with 2-5 g of fiber). For the third meal, a weekly menu plan with recipes was given to the participants. This meal was composed of traditional foods, was low in fat, high in vegetables but allowed for individual preferences, and provided 500-750 kcal. In addition, up to three snacks (\
100 kcal each) were allowed each day. The macronutrient goal for each individual was \
55-60% carbohydrates, \
15% protein, and \
25% fat. | 22 |
| Hypocaloric Weight Loss + Pioglitazone Two meal replacements per day (bars and shakes) were provided to all participants (containing \
220 kcal with 7-10 g protein, 33-46 g carbohydrates, and 1.5-5 g fat with 2-5 g of fiber). For the third meal, a weekly menu plan with recipes was given to the participants. This meal was composed of traditional foods, was low in fat, high in vegetables but allowed for individual preferences, and provided 500-750 kcal. In addition, up to three snacks (\
100 kcal each) were allowed each day.
Pioglitazone was given an initial 15 mg/day dose. Participants were assessed for side effects after 3 weeks, but none were reported. Therefore, after 3 weeks, the dose was increased to 30 mg/day for the remainder of the study for all participants randomized to receive pioglitazone. In order to understand the potential effects of changes in body composition independent of drug effects, a 1-week wash-out period preceded the follow-up outcome assessment. | 22 |
| Hypocaloric Weight-loss +Resistance Training Two meal replacements per day (bars and shakes) were provided to all participants (containing \
220 kcal with 7-10 g protein, 33-46 g carbohydrates, and 1.5-5 g fat with 2-5 g of fiber). For the third meal, a weekly menu plan with recipes was given to the participants. This meal was composed of traditional foods, was low in fat, high in vegetables but allowed for individual preferences, and provided 500-750 kcal. In addition, up to three snacks (\
100 kcal each) were allowed each day.
The goal of the resistance training program was to increase strength and muscle mass in the major muscle groups of the body, while also improving muscle power in the lower extremity. Participants randomized to the resistance training exercised 3 days/week. Participants warmed-up by walking or cycling for 3-5 min at a slow pace followed by 5 min of large muscle flexibility exercises targeting the major muscle groups of the body. Training sessions ended with a cool-down session of light stretching. | 22 |
| Hypocaloric Weight Loss + Resistance Training + Pioglitazone Two meal replacements per day (bars and shakes) were provided to all participants (containing \
220 kcal with 7-10 g protein, 33-46 g carbohydrates, and 1.5-5 g fat with 2-5 g of fiber). For the third meal, a weekly menu plan with recipes was given to the participants.
The goal of the resistance training program was to increase strength and muscle mass in the major muscle groups of the body, while also improving muscle power in the lower extremity. Participants randomized to the resistance training exercised 3 days/week. Participants warmed-up by walking or cycling for 3-5 min at a slow pace followed by 5 min of large muscle flexibility exercises targeting the major muscle groups of the body.
Pioglitazone was given an initial 15 mg/day dose. Participants were assessed for side effects after 3 weeks. Therefore, after 3 weeks, the dose was increased to 30 mg/day for the remainder of the study for all participants randomized to receive pioglitazone. | 22 |
| Total | 88 |
Baseline characteristics
| Characteristic | Hypocaloric Weight Loss + Pioglitazone | Hypocaloric Weight-loss +Resistance Training | Hypocaloric Weight Loss Only | Hypocaloric Weight Loss + Resistance Training + Pioglitazone | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 22 Participants | 22 Participants | 22 Participants | 22 Participants | 88 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 70.4 years STANDARD_DEVIATION 3.5 | 71.0 years STANDARD_DEVIATION 4.3 | 71.0 years STANDARD_DEVIATION 3.9 | 69.9 years STANDARD_DEVIATION 2.7 | 70.6 years STANDARD_DEVIATION 3.6 |
| Region of Enrollment United States | 22 participants | 22 participants | 22 participants | 22 participants | 88 participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 40 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 12 Participants | 12 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 |
| serious Total, serious adverse events | 3 / 22 | 0 / 22 | 0 / 22 | 0 / 22 |
Outcome results
Primary
Appendicular Non-bone Lean Mass
Change in Appendicular Non-bone Lean Mass
Time frame: Baseline visit (pre intervention) and 4month follow up (post intervention)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Hypocaloric Weight Loss Only | Appendicular Non-bone Lean Mass | -2.53 kg |
| Hypocaloric Weight Loss + Pioglitazone | Appendicular Non-bone Lean Mass | -2.49 kg |
| Hypocaloric Weight-loss +Resistance Training | Appendicular Non-bone Lean Mass | -2.04 kg |
| Hypocaloric Weight Loss + Resistance Training + Pioglitazone | Appendicular Non-bone Lean Mass | -1.45 kg |
Secondary
Lean Body Mass
Time frame: Baseline visit (pre intervention) and 4month follow up (post intervention)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Hypocaloric Weight Loss Only | Lean Body Mass | -2.55 kg |
| Hypocaloric Weight Loss + Pioglitazone | Lean Body Mass | -1.89 kg |
| Hypocaloric Weight-loss +Resistance Training | Lean Body Mass | -2.38 kg |
| Hypocaloric Weight Loss + Resistance Training + Pioglitazone | Lean Body Mass | -1.65 kg |