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

NCT ID: NCT04424537

Last Updated: 2022-08-04

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: EARLY_PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-31
• Study Completion Date: 2028-01-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Control

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.

Group Type: PLACEBO_COMPARATOR

Control diet

Intervention Type: DIETARY_SUPPLEMENT

Meal replacement beverages made with whey protein

Low protein(LP) diet

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.

Group Type: ACTIVE_COMPARATOR

Low protein diet

Intervention Type: DIETARY_SUPPLEMENT

meal replacement beverages(MRBs) containing low protein

Low branched-chain amino acids (BCAA)

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.

Group Type: EXPERIMENTAL

Low branched-chain amino acids(BCAA) diet

Intervention Type: DIETARY_SUPPLEMENT

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

Interventions

Control diet

Meal replacement beverages made with whey protein

Intervention Type: DIETARY_SUPPLEMENT

Low branched-chain amino acids(BCAA) diet

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

Intervention Type: DIETARY_SUPPLEMENT

Low protein diet

meal replacement beverages(MRBs) containing low protein

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Pregnancy or plans to conceive within 4 months of visit 1

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dawn B Davis, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Wisconsin-Madison School of Medicine and Public Health

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

A534245

Identifier Type: OTHER

Identifier Source: secondary_id

SMPH/MEDICINE/ENDOCRINOL

Identifier Type: OTHER

Identifier Source: secondary_id

Protocol Version 3/1/2021

Identifier Type: OTHER

Identifier Source: secondary_id

2019-0701

Identifier Type: -

Identifier Source: org_study_id