SOAR-2: Intervening in Obesity Through Reduction of Dietary Branched Chain Amino Acids

NCT04424537 | Withdrawn Early Phase 1 DMC

• 4 other identifiers: 2019-0701A534245SMPH/MEDICINE/ENDOCRINOLProtocol Version 3/1/2021
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

One of the primary risk factors for the development of diabetes is obesity. While even moderate weight loss achieved by dieting can lead to improvements in metabolic health, reduced-calorie diets are notoriously difficult to sustain. Over the past decade, a number of groups have shown that low protein diets are associated with metabolic health in both rodents and humans. In particular, specific building blocks of protein- the branched chain amino acids (BCAAs) leucine, isoleucine, and valine - are associated with insulin resistance and diabetes in humans. Blood levels of the BCAAs decrease in humans fed a low protein diet, and we recently showed that reducing either dietary BCAAs or protein rapidly restored normal body composition and insulin sensitivity to diet-induced obese mice without reducing calorie intake. Current study will test the metabolic role of dietary BCAAs in humans by completing an adequately powered, randomized controlled study. A total of 132 subjects stratified by gender will be randomized to one of three groups: 1) Control; 2) Low Protein; 3) Low BCAA. Subjects in each group will replace two meals a day (and 2/3rds of their baseline dietary protein) with meal replacement beverages based on either complete protein powder or a BCAA-free medical food for two months. Primary outcomes will be weight and fasting blood glucose levels. A number of secondary outcomes will also be assessed and blood, adipose, and fecal samples will be collected for integrated transcriptional and metabolomic pathway analysis to identify and compare the metabolic pathways affected by low protein and low BCAA diets.

Conditions

Obesity; Diabetes

Keywords

Calorie restriction

Outcome Measures

Primary Outcomes (2)

• Change in weight

  Change in participant weight

  Baseline, 30 (±7)days, 60(-3 to +7)days, 134(+7) days

• Change in fasting blood glucose level

  Change in the participant's fasting blood glucose level

  Baseline, 30 (±7)days, 60(-3 to +7)days, 134(+7) days

Secondary Outcomes (7)

• Change in the body composition (adipose mass) as measured by DXA/BIS

  Baseline, 60(-3 to +7)days

• Change in Insulin sensitivity

  Baseline, 30 (±7)days, 60(-3 to +7)days, 134(+7) days

• Change in Fibroblast growth factor 21 (FGF21) levels

  Baseline, 30 (±7)days, 60(-3 to +7)days

• Change in Energy expenditure as measured by resting metabolic rate

  Baseline, 60(-3 to +7)days

• Change in Muscle function as measured by jump maximal height

  Baseline, 60(-3 to +7)days

Study Arms (3)

Control

PLACEBO COMPARATOR

A control group will consume 2 meal replacement beverages(MRBs) made with whey protein The control diet group will be provided with a protein powder which will provide all Amino Acids. Diets will be provided in unmarked containers, to ensure subjects will be blinded to the dietary group assignment. No overall calorie reduction will be implemented for any group. All subjects will receive recipes developed by clinical nutritionist in the study team. Theses recipes will maximize palatability and match energy density across all diets and total protein content. The subjects will be able to use multiple different recipes over the course of the study to prevent taste fatigue and dropout. Each subject is anticipated to replace 2 meals per day with a beverage.

Dietary Supplement: Control diet

Low protein(LP) diet

ACTIVE COMPARATOR

This group will consume 2 meal replacement beverages(MRBs) containing low protein (goal to reduce total protein by 2/3rds). LP diet group will be provided with a protein powder which will provide all Amino Acids. Diets will be provided in unmarked containers, to ensure subjects will be blinded to the dietary group assignment. No overall calorie reduction will be implemented for any group. All subjects will receive recipes developed by clinical nutritionist in the study team. Theses recipes will maximize palatability and match energy density across all diets and total protein content. The subjects will be able to use multiple different recipes over the course of the study to prevent taste fatigue and dropout. Each subject is anticipated to replace 2 meals per day with a beverage.

Dietary Supplement: Low protein diet

Low branched-chain amino acids (BCAA)

EXPERIMENTAL

The group on low-BCAA diet will consume 2 meal replacement beverages (MRBs) per day made with BCAD2 (branched chain amino acid) powder (lacking BCAAs). BCAD2 powder(Mead Johnson) is a fortified medical food powder that does not contain the BCAAs isoleucine, leucine, or valine, but provides all other essential and nonessential AAs, carbohydrates, fat, vitamins, and minerals. No overall calorie reduction will be implemented for any group. All subjects will receive recipes developed by clinical nutritionist in the study team. Theses recipes will maximize palatability and match energy density across all diets and total protein content. The subjects will be able to use multiple different recipes over the course of the study to prevent taste fatigue and dropout. Each subject is anticipated to replace 2 meals per day with a beverage.

Dietary Supplement: Low branched-chain amino acids(BCAA) diet

Interventions

Control diet DIETARY_SUPPLEMENT

Meal replacement beverages made with whey protein

Control

Low branched-chain amino acids(BCAA) diet DIETARY_SUPPLEMENT

meal replacement beverages (MRBs) made with BCAD2 powder (lacking BCAAs).

Low branched-chain amino acids (BCAA)

Low protein diet DIETARY_SUPPLEMENT

meal replacement beverages(MRBs) containing low protein

Low protein(LP) diet

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI between 28 - 40 (overweight to obese)
• Baseline protein intake within normal adult ranges (15.1%-20.8% of calories from protein)
• Able and willing to give written informed consent
• Stable weight (within 5 lbs. for at least 3 months)
• Not taking (or willing to cease taking) vitamin/mineral supplements, unless prescribed for a specific medical disorder
• Not planning to begin a new exercise or diet program

You may not qualify if:

• Use of prescription medications for diabetes or weight-loss
• Diabetes - fasting glucose level of greater than 125 mg/dL and/or hemoglobin A1C( HbA1c or A1C) above 6.4%
• Use of and unwillingness to discontinue weight loss beverage or meal plans (e.g. SlimFast or Jenny Craig)
• Low baseline albumin or pre-albumin levels (below normal reference range)
• Significant anemia (Hemoglobin \< 11 g/dL)
• Known bleeding disorder or platelet dysfunction
• Participating in intensive exercise training program (high to moderate intensity exercise greater than 210 minutes per week) or planning to start new exercise program during study period.
• Significant co-morbidities (including kidney disease, liver disease, GI disease, cardiovascular disease, respiratory disease, malnutrition, substance abuse, psychiatric disease, or a diagnosed eating disorder).
• Planned smoking cessation or attempt at smoking cessation during study period
• Inability to tolerate meal replacement beverages due to palatability
• Bariatric surgery, gastric banding or liposuction
• Current or past (within 1 year) use of illicit drugs
• Use of and unwillingness to cease taking vitamin/mineral supplements and other over the counter supplements (e.g.,cinnamon, protein powders) that are known to affect weight and/or glucose tolerance, unless prescribed for a specific medical disorder
• Allergy to racemethionine
• Lactose intolerance

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin-Madison School of Medicine and Public Health

Madison, Wisconsin, 53726, United States

Location

MeSH Terms

Conditions

Obesity; Diabetes Mellitus

Interventions

Diet; Diet, Protein-Restricted

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Diet Therapy; Nutrition Therapy; Therapeutics

Study Officials

• Dawn B Davis, MD, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2020
• First Posted: June 11, 2020
• Study Start: January 1, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: August 4, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)