Utilizing Protein During Weight Loss to Impact Physical Function

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the effects of diet composition (i.e., amount of protein and carbohydrate) during a 6-month weight loss intervention and 12-months of follow-up on physical function, muscle mass, and weight loss maintenance in obese older adults. Participants will receive either a protein or carbohydrate supplement along with a behavioral weight loss intervention.

Detailed Description
-----------------
The study will use a 3-group design in 225 obese (BMI 27-45 kg/m2), older (65-85 years) men and women at risk for disability (eSPPB <2.5) who will undergo a 6-month weight loss intervention followed by a 12-month follow-up phase to test the overall hypothesis that a higher protein (1.2 g/kg body wt/d) / lower carbohydrate (CHO) diet during a 6-month weight loss intervention improves physical function compared with an isocaloric lower protein (the current Recommended Dietary Allowance (RDA), 0.8 g/kg body wt/d) / higher CHO diet, and whether continuing a higher protein / lower CHO diet for 12-months following weight loss will result in better maintenance of improved physical function. All participants will undergo a 6-month weight loss intervention involving caloric restriction and supervised exercise followed by 12 months of follow-up with randomization to one of three groups (n=75/group): 1) Lower protein / higher CHO diet for the 6-month weight loss phase only (RecProt); 2) Higher protein / lower CHO diet for the 6-month weight loss phase only (6-mo HiProt); or 3) Higher protein / lower CHO diet for the 6-month weight loss and 12-month follow-up phases (18-mo HiProt). Physical function (primary aim) will be assessed by the expanded Short Physical Performance Battery (primary outcome) and lower extremity muscle strength at baseline, 6-, 12- and 18-months. Weight loss maintenance and body composition (secondary aim) will be assessed by dual-energy X-ray absorptiometry (DXA) and computed tomography (CT) at baseline, 6- and 18-months. Bone mineral density (DXA) and cardiometabolic risk factors will also be measured at baseline, 6- and 18-months.

Official Title
-----------------
Long-term Effects of Weight Loss and Supplemental Protein on Physical Function

Conditions
-----------------
Obesity, Weight Loss, Diet Modification, Aging, Weight Change, Body, Dietary Habits

Intervention / Treatment
-----------------
* Behavioral: Weight loss intervention months 0-6
* Behavioral: Exercise intervention months 0-6
* Dietary Supplement: Carbohydrate supplement for months 0-6
* Dietary Supplement: Protein supplement for months 0-6
* Dietary Supplement: Protein supplement for follow-up months 7-18


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 65-85 years BMI: 27-45 kg/m2 No regular resistance training and/or aerobic exercise (>20 mins/d) for past 6 months eSPPB <2.5 No contraindications for safe and optimal participation in exercise training Approved for participation by Medical Director (Dr. Lyles) Willing to provide informed consent Agree to all study procedures and assessments Willing to consume protein/CHO supplements for up to 18 months Able to provide own transportation to study visits and intervention sessions Exclusion Criteria: Weight loss (≥5%) in past 6 months Dependent on cane or walker Cognitive impairment (MoCA score <22) Severe arthritis, or other musculoskeletal disorder Joint replacement or other orthopedic surgery in past 6 months Uncontrolled resting hypertension (>160/90 mmHg); Insulin-dependent or uncontrolled diabetes (HbA1c ≥8%) Current or recent past (within 1 year) severe symptomatic heart disease, uncontrolled angina, stroke, chronic respiratory disease requiring oxygen; uncontrolled endocrine/metabolic disease; neurological or hematological disease; cancer requiring treatment in past year, except non-melanoma skin cancers; liver or renal disease; or clinically evident edema Unstable, severe depression Serious conduction disorder, uncontrolled arrhythmia, or new Q waves or ST-segment depressions (>3 mm at rest or ≥2 mm with exercise) Abnormal kidney function (eGFR <30 based on serum creatinine, age, gender, and race) Anemia (Hb<13 g/dL in men; <12 g/dL in women) Drug abuse or excessive alcohol use (>7 drinks/week women; >14 drinks/week men) Use of any tobacco or nicotine products in the past year Osteoporosis (T-score < -2.5 on hip or spine scan) Regular use of growth/steroid hormones, sex steroids or corticosteroids, osteoporosis medication, or protein supplements Weight loss medications or procedures Current participation in another intervention 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
Interventional Model Description: All participants will undergo a 6-month weight loss intervention of caloric restriction and supervised exercise followed by 12 months of follow-up with randomization to one of three groups (n=75/group): 1) Lower protein / higher CHO diet for the 6-month weight loss phase only (RecProt); 2) Higher protein / lower CHO diet for the 6-month weight loss phase only (6-mo HiProt); or 3) Higher protein / lower CHO diet for the 6-month weight loss and 12-month follow-up phases (18-mo HiProt).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: RecProt<br>Lower protein / higher CHO diet for the 6-month weight loss phase. Exercise intervention months 0-6. Weight loss intervention months 0-6. Carbohydrate supplement for months 0-6 (blinded). Follow-up months 7-18. | Behavioral: Weight loss intervention months 0-6<br>* All participants will undergo a dietary weight loss intervention designed to elicit behavioral changes leading to decreased caloric intake sufficient to yield a  10% loss of initial body mass. The weight loss intervention will incorporate nutrition education (via group and individual meetings with the study dietitian), self-monitoring skills, cognitive-behavioral strategies for promoting lifestyle behavior modifications, and planned meals. Behavioral and educational group and individual sessions will be held weekly in a 3:1 ratio (3 group and 1 individual session per month).<br>Behavioral: Exercise intervention months 0-6<br>* All participants will be expected to participate in a supervised, center-based exercise program involving moderate-intensity aerobic exercise (e.g., treadmill walking) 3 days/wk during the 6-month weight loss intervention in accordance with the American Heart Association and the American College of Sports Medicine physical activity recommendations for older adults.<br>Dietary Supplement: Carbohydrate supplement for months 0-6<br>* Participants in the lower protein / higher CHO diet group (RecProt) will be provided a carbohydrate supplement ( 50 g of carbohydrate and 220 calories) to consume daily during the 6 month weight loss intervention.<br>|
| Active Comparator: 6-mon HiProt<br>Higher protein / lower CHO diet for the 6-month weight loss phase. Exercise intervention months 0-6. Weight loss intervention months 0-6. Protein supplement for months 0-6 (blinded). Follow-up months 7-18. | Behavioral: Weight loss intervention months 0-6<br>* All participants will undergo a dietary weight loss intervention designed to elicit behavioral changes leading to decreased caloric intake sufficient to yield a  10% loss of initial body mass. The weight loss intervention will incorporate nutrition education (via group and individual meetings with the study dietitian), self-monitoring skills, cognitive-behavioral strategies for promoting lifestyle behavior modifications, and planned meals. Behavioral and educational group and individual sessions will be held weekly in a 3:1 ratio (3 group and 1 individual session per month).<br>Behavioral: Exercise intervention months 0-6<br>* All participants will be expected to participate in a supervised, center-based exercise program involving moderate-intensity aerobic exercise (e.g., treadmill walking) 3 days/wk during the 6-month weight loss intervention in accordance with the American Heart Association and the American College of Sports Medicine physical activity recommendations for older adults.<br>Dietary Supplement: Protein supplement for months 0-6<br>* Participants in the higher protein / lower CHO diet groups (6-mon HiProt and 18-mon HiProt) will be provided a protein supplement ( 50 g of protein and 220 calories) to consume daily during the 6 month weight loss intervention.<br>|
| Active Comparator: 18-mon HiProt<br>Higher protein / lower CHO diet for the 6-month weight loss and 12-month follow-up phases. Exercise intervention months 0-6. Weight loss intervention months 0-6. Protein supplement for months 0-6 (blinded). Protein supplement for follow-up months 7-18. | Behavioral: Weight loss intervention months 0-6<br>* All participants will undergo a dietary weight loss intervention designed to elicit behavioral changes leading to decreased caloric intake sufficient to yield a  10% loss of initial body mass. The weight loss intervention will incorporate nutrition education (via group and individual meetings with the study dietitian), self-monitoring skills, cognitive-behavioral strategies for promoting lifestyle behavior modifications, and planned meals. Behavioral and educational group and individual sessions will be held weekly in a 3:1 ratio (3 group and 1 individual session per month).<br>Behavioral: Exercise intervention months 0-6<br>* All participants will be expected to participate in a supervised, center-based exercise program involving moderate-intensity aerobic exercise (e.g., treadmill walking) 3 days/wk during the 6-month weight loss intervention in accordance with the American Heart Association and the American College of Sports Medicine physical activity recommendations for older adults.<br>Dietary Supplement: Protein supplement for months 0-6<br>* Participants in the higher protein / lower CHO diet groups (6-mon HiProt and 18-mon HiProt) will be provided a protein supplement ( 50 g of protein and 220 calories) to consume daily during the 6 month weight loss intervention.<br>Dietary Supplement: Protein supplement for follow-up months 7-18<br>* Participants in the higher protein / lower CHO diet (18-mon HiProt) will be provided a protein supplement ( 50 g of protein and 220 calories) to consume daily during the 12-month follow-up.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Expanded Short Physical Performance Battery Score | To determine the effects of a higher protein / lower CHO diet vs. lower protein / higher CHO diet during a 6-month weight loss intervention and 12 months of follow-up on change in lower extremity physical function assessed by the expanded Short Physical Performance Battery score over 18 months. The expanded Short Physical Performance Battery score ranges from 0 to 4 with higher scores indicating better lower extremity physical function | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lower Extremity Muscle Strength | To determine the effects of a higher protein / lower CHO diet vs. lower protein / higher CHO diet during a 6-month weight loss intervention and 12 months of follow-up on change in lower extremity muscle strength assessed using an isokinetic dynamometer (Biodex) over 18 months | 18 months | 
| Weight Change | To determine the effects of a higher protein / lower CHO diet vs. lower protein / higher CHO diet during a 6-month weight loss intervention and 12 months of follow-up on change in body weight over 18 months | 18 months | 
| Total Body Lean Mass | To determine the effects of a higher protein / lower CHO diet vs. lower protein / higher CHO diet during a 6-month weight loss intervention and 12 months of follow-up on change in dual energy x-ray (DXA) acquired total body lean mass over 18 months | 18 months | 
| Total Body Fat Mass | To determine the effects of a higher protein / lower CHO diet vs. lower protein / higher CHO diet during a 6-month weight loss intervention and 12 months of follow-up on change in dual energy x-ray acquired (DXA) total body fat mass over 18 months | 18 months | 
| Thigh Muscle Volume | To determine the effects of a higher protein / lower CHO diet vs. lower protein / higher CHO diet during a 6-month weight loss intervention and 12 months of follow-up on change in computerized tomography (CT) acquired thigh muscle volume over 18 months | 18 months | 
| Intermuscular Adipose Tissue | To determine the effects of a higher protein / lower CHO diet vs. lower protein / higher CHO diet during a 6-month weight loss intervention and 12 months of follow-up on change in computerized tomography (CT) acquired thigh intermuscular adipose tissue over 18 months | 18 months |