Utilizing Protein During Weight Loss to Impact Physical Function and Bone

Study Overview
=================
Brief Summary
-----------------
This study is an ancillary study to the Utilizing Protein During Weight Loss to Impact Physical Function (UPLIFT) trial (NCT03074643) to 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 bone phenotypes in obese older adults. Participants will receive either a protein or carbohydrate supplement along with a behavioral weight loss intervention.

Detailed Description
-----------------
The ancillary study to the UPLIFT trial (NCT03074643) will use a 3-group design in 225 obese (body mass index [BMI] 30-45 kg/m2 or 27-<30 kg/m2 with an obesity-related risk factor), older (65-85 years) men and women at risk for disability (Short Physical Performance Battery, SPPB ≤10) 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 weight/day) / lower carbohydrate (CHO) diet during a 6-month weight loss intervention improves bone phenotypes 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 bone. 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). Vertebral and femoral volumetric bone mineral density and cortical thickness (Primary Aim) and bone marrow adipose tissue (Secondary Aim 1) will be assessed with computed tomography at baseline, 6-, and 18-months. Bone strength and fracture risk (Secondary Aim 2) will be assessed by finite element modeling at baseline, 6-, and 18-months.

Official Title
-----------------
Effect of Protein Supplementation During Weight Loss on Older Adult Bone Health

Conditions
-----------------
Obesity, Weight Loss, Diet Modification, Aging, Weight Change, Body, Dietary Habits, Osteopenia, Osteoporosis, Bone Loss, Fractures, Bone

Intervention / Treatment
-----------------
* Behavioral: Weight loss intervention months 0-6
* Behavioral: Exercise intervention months 0-6
* Dietary Supplement: NutraBio™ CarboMax Supplement
* Dietary Supplement: 6-month NutraBio™ 100% Whey Protein Isolate Supplement
* Dietary Supplement: 18-month NutraBio™ 100% Whey Protein Isolate Supplement


Participation Criteria
=================
Eligibility Criteria
-----------------
Subjects are recruited using inclusion and exclusion criteria of the parent trial (UPLIFT; NCT03074643). Inclusion Criteria: 65-85 years BMI: 30-45 kg/m2 or BMI 27.0 - <30.0 AND at least one of the following risk factors: elevated waist circumference (>35 inches in women, >40 inches in men) diabetes, hypertension, dyslipidemia, or other obesity-related comorbidities: clinically manifest coronary artery disease [e.g., history of myocardial infarction, angina pectoris, coronary artery surgery, coronary artery procedures (e.g., angioplasty) if not within the past year], other atherosclerotic disease [e.g., peripheral arterial disease, abdominal aortic aneurysm, symptomatic carotid artery disease if not within the past year], sleep apnea, or osteoarthritis of the knee or hip. No regular resistance training and/or aerobic exercise (>20 mins/d) for past 6 months SPPB ≥3 to ≤10 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 (Montreal Cognitive Assessment, MoCA score <22) Severe arthritis, or other musculoskeletal disorder Joint replacement or other orthopedic surgery in past year Uncontrolled resting hypertension (>160/90 mmHg); Uncontrolled diabetes (hemoglobin A1c, HbA1c ≥8.0%) 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 (estimated glomerular rate <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 Protein supplements (and unwilling to stop using for duration of study) 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 |
| --- | --- |
| Active Comparator: RecProt<br>Subjects receiving the following interventions in the parent trial (UPLIFT; NCT03074643): 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: NutraBio™ CarboMax Supplement<br>* Participants in the lower protein / higher CHO diet group (RecProt) will be provided a carbohydrate supplement (NutraBio™ CarboMax,  50 g of carbohydrate and 220 calories) to consume daily during the 6 month weight loss intervention.<br>|
| Active Comparator: 6-mo HiProt<br>Subjects receiving the following interventions in the parent trial (UPLIFT; NCT03074643): 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: 6-month NutraBio™ 100% Whey Protein Isolate Supplement<br>* Participants in the 6-month higher protein / lower CHO diet group (6-mo HiProt) will be provided a protein supplement (NutraBio™ 100% Whey Protein Isolate,  50 g of protein and 220 calories) to consume daily during the 6 month weight loss intervention.<br>|
| Active Comparator: 18-mo HiProt<br>Subjects receiving the following interventions in the parent trial (UPLIFT; NCT03074643): 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: 18-month NutraBio™ 100% Whey Protein Isolate Supplement<br>* Participants in the 18-month higher protein / lower CHO diet (18-mo HiProt) will be provided a protein supplement (NutraBio™ 100% Whey Protein Isolate,  50 g of protein and 220 calories) to consume daily during the 6 month weight loss intervention and the 12-month follow-up.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Femoral volumetric bone mineral density assessed by computed tomography (CT) | 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 18-month femoral volumetric bone mineral density | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fraction of adipose tissue within the bone marrow as assessed by a dual-energy computed tomography algorithm | To determine the effects of a higher protein / lower CHO diet vs. lower protein / higher CHO diet during a 6-month weight loss intervention on the 6-month fraction of adipose tissue within the bone marrow as assessed by a dual-energy computed tomography algorithm | 6 months | 
| Fraction of adipose tissue within the bone marrow as assessed by a dual-energy computed tomography algorithm | 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 the 18-month fraction of adipose tissue within the bone marrow as assessed by a dual-energy computed tomography algorithm | 18 months | 
| Femoral bone strength as assessed by subject-specific finite element modeling | To determine the effects of a higher protein / lower CHO diet vs. lower protein / higher CHO diet during a 6-month weight loss intervention on 6-month femoral bone strength as assessed by subject-specific finite element modeling | 6 months | 
| Femoral bone strength as assessed by subject-specific finite element modeling | 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 18-month femoral bone strength as assessed by subject-specific finite element modeling | 18 months | 
| Femoral cortical thickness as assessed by a computed tomography based algorithm | 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 18-month femoral cortical thickness as assessed by a computed tomography based algorithm | 18 months | 
| Femoral cortical thickness as assessed by a computed tomography based algorithm | To determine the effects of a higher protein / lower CHO diet vs. lower protein / higher CHO diet during a 6-month weight loss intervention on 6-month femoral cortical thickness as assessed by a computed tomography based algorithm | 6 months | 
| Vertebral volumetric bone mineral density | 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 18-month vertebral volumetric bone mineral density | 18 months | 
| Vertebral volumetric bone mineral density | To determine the effects of a higher protein / lower CHO diet vs. lower protein / higher CHO diet during a 6-month weight loss intervention on 6-month vertebral volumetric bone mineral density. | 6 months | 
| Femoral volumetric bone mineral density | To determine the effects of a higher protein / lower CHO diet vs. lower protein / higher CHO diet during a 6-month weight loss intervention on 6-month femoral volumetric bone mineral density | 6 months |