Lifestyle Intervention Trial in Obese Elderly

Study Overview
=================
Brief Summary
-----------------
Obesity causes frailty in obese older adults by exacerbating the age-related decline in physical function. However, appropriate management of obesity in older adults is controversial. Weight loss without exercise could worsen frailty by accelerating the usual age-related decline in muscle and bone mass that leads to sarcopenia and osteopenia, respectively. Because of the important problem of frailty in obese older adults, it is important to determine the most efficacious approach in reducing, or even reversing frailty in this population. The primary objective of this proposal is to evaluate which distinct type of physical exercise (resistance, aerobic, or combined resistance + aerobic) is most efficacious in preventing the weight-loss-induced reduction in muscle and bone mass and reversing frailty in obese older adults.

Official Title
-----------------
Exercise Interventions During Voluntary Weight Loss in Obese Older Adults

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Behavioral: Diet + Resistance Training
* Behavioral: Diet + Aerobic Training
* Behavioral: Diet + Resistance/Aerobic Exercise


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 65-85 years old Obese men and women (BMI > or equal to 30 kg/m2) Stable weight (±2 kg) during the last 6 mos. Must be sedentary (regular exercise <1 h/wk or <2 x/wk for the last 6 mos.) Be judged, during the initial screening, to be well motivated and reliable Exclusion Criteria: Any major chronic diseases Any condition or unstable diseases that would interfere with exercise or dietary restriction, in which exercise or dietary restriction are contraindicated, or that would interfere with interpretation of results that include but are not limited to: Cardiopulmonary disease (e.g., recent MI, unstable angina, stroke etc.) Severe orthopedic/musculoskeletal or neuromuscular impairments that would contraindicate participation in exercise Visual or hearing impairments that interfere with following directions Diagnosis of dementia History of malignancy during the past 5 yr Recent use of bone acting drugs (e.g. use of estrogen, or androgen containing compound, raloxifene, calcitonin, parathyroid hormone during the past year or biphosphonates during the last two years) Individuals on insulin or with a fasting blood glucose of > 140mg/dl, and/or a 2 hour post-glucose of >250 mg/dl BMD t-scores of <-2.3 of the lumbar spine and proximal femur serum creatinine >2.0 mg/dl No commitments, life situations or conditions that would interfere with their participation in the study

Ages Eligible for Study
-----------------
Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diet + Resistance Exercise Training<br>Weekly behavioral/diet-induced weight loss plus supervised resistance exercise training three times a week | Behavioral: Diet + Resistance Training<br>* Behavioral Therapy through a lifestyle modification program, Diet therapy once weekly through a dietician prescribed diet for 26 weeks, and resistance exercise training 3-days/week for 24 weeks.<br>|
| Experimental: Diet + Aerobic Exercise Training<br>Weekly behavioral/diet-induced weight loss plus supervised aerobic exercise training three times a week | Behavioral: Diet + Aerobic Training<br>* Behavioral Therapy through a lifestyle modification program, Diet therapy once weekly through a dietician prescribed diet for 26 weeks, and aerobic exercise training 3-days/week for 24 weeks<br>|
| Experimental: Diet + Combined Aerobic/Resistance Exercise<br>Weekly behavioral/diet-induced weight loss plus combined supervised resistance exercise training and aerobic exercise training three times a week | Behavioral: Diet + Resistance/Aerobic Exercise<br>* Behavioral Therapy through a lifestyle modification program, Diet therapy once weekly through a dietician prescribed diet for 26 weeks, and combined resistance/aerobic exercise training 3-days/week for 24 weeks<br>|
| No Intervention: Control Group (No Diet/No Exercise)<br>No diet No exercise training | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Physical Function | The Physical Performance Test includes seven standardized tasks (walking 15.2 m [50 ft], putting on and removing a coat, picking up a penny, standing up from a chair, lifting a book, climbing one flight of stairs, and performing a progressive Romberg test) plus two additional tasks (going up and down four flights of stairs and making a 360-degree turn). The score for each task ranges from 0 to 4, with higher scores indicating better physical performance; a perfect score would be 36. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lean mass | Assessed using dual energy x-ray absorptiometry (DXA) | 6 months | 
| Change in fat mass | Assessed using DXA | 6 months | 
| Change in muscle strength | Assessed using 1-repetition maximum and dynamometry | 6 months | 
| Change in gait speed | Measured as time to walk a certain distance | 6 months | 
| Change in areal bone mineral density | Assessed by using DXA | 6 months | 
| Change in biochemical marker for bone turnover and bone metabolism | Assessed by using enzyme linked immunoabsorbent assay and radioimmunoassay | 6 months | 
| Change in circulating cytokines | Assessed by using enzyme linked immunoassay | 6 months | 
| Change in adipocytokines | Assessed by using enzyme linked immunoassay | 6 months | 
| Change in aerobic capacity | Assessed by using indirect calorimetry during graded exercise stress test | 6 months | 
| Change in systolic and diastolic blood pressure | Assessed by using sphygmomanometer | 6 months | 
| Change in serum glucose | Assessed by glucose oxidase method | 6 months | 
| Change in serum lipids | Assessed by automated enzymatic/colorimetric assays | 6 months | 
| Change in habitual physical activity assessed by questionnaires | Using the Stanford physical activity questionnaire (score range: 0 to 40 with higher scores indicating higher physical activity levels) | 6 months | 
| Change in habitual physical activity measured objectively | Using accelerometers | 6 months | 
| Change in serum insulin | Assessed by immunoassay | 6 months | 
| Change in serum estradiol | Assessed by immunoassay | 6 months | 
| Change in 25 hydroxyvitamin D | Assessed by immunoassay | 6 months | 
| Change in Impact of Weight on Quality of Life_Lite (IWQOL-lite) score | Assessed by IWQO-liteL questionnaire | 6 months | 
| Change in Medical Outcomes 36-Item short form Health survey (SF-36) | Assessed by Physical component summary and mental component summary score (score range 0 to 100, with higher scores indicating better health status) | 6 months | 
| Change in gene expression of muscle anabolic and catabolic factors | Assessed by reverse transcription polymerase chain reaction and nanostring | 6 months | 
| Change in protein expression of muscle anabolic and catabolic factors | Assessed by western blotting | 6 months | 
| Change in concentration of targeted metabolites | Assessed by liquid chromatography hyphenated with mass spectrometry techniques | 6 months | 
| Change in dynamic balance | Assessed by the obstacle course | 6 months | 
| Change in static balance | Assessed by one leg stance | 6 months | 
| Change in modified mini-mental exam | Assessed by using cognitive instrument testing | 6 months | 
| Change in word fluency | Assessed by using cognitive instrument testing | 6 months | 
| Change in trail a and trail b | Assessed by using cognitive instrument testing | 6 months | 
| Change in Ray Auditory verbal learning test | Assessed by using cognitive instrument testing | 6 months | 
| Change in muscle protein synthesis rate | Assessed by stable isotope methodology | 6 months | 
| Change in thigh muscle and fat mass | Assessed by magnetic resonance imaging (MRI) | 6 months | 
| Change in visceral fat mass | Assessed by MRI | 6 months | 
| Change in mood | Assessed by geriatric depression scale (score range: 0 to 30, where lower scores indicating better mood) | 6 months | 
| Change in waist circumference | Using a tape measure | 6 months | 
| Change in serum testosterone | Assessed by immunoassay | 6 months | 
| Change in subjective ability to function | Assessed by Functional Status Questionnaire (score range: 0 to 36 with higher scores indicating better function) | 6 months | 
| Change is serum sclerostin | Assessed by immunoassay | 6 months | 
| Change in parathyroid hormone | Assessed by immunoassay | 6 months |