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

Primary Purpose

Obesity, Diabetes

Status

Withdrawn

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Control diet

Low branched-chain amino acids(BCAA) diet

Low protein diet

About this trial

This is an interventional basic science trial for Obesity focused on measuring Calorie restriction

Eligibility Criteria

30 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

University of Wisconsin-Madison School of Medicine and Public Health

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Experimental

Arm Label

Control

Low protein(LP) diet

Low branched-chain amino acids (BCAA)

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Change in weight

Change in participant weight

Change in fasting blood glucose level

Change in the participant's fasting blood glucose level

Secondary Outcome Measures

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

Dual energy X-ray absorptiometry (DXA) is a standard technique for the determination of body composition. DXA results will be used to calculate fat and lean mass composition. Total body Bioelectrical Impedance Spectroscopy (BIS) is a minimal risk procedure which enhances DXA as it permits the determination of intracellular water.BIS is used to calculate fat and fat-free mass composition. A formula will be used to combine BIS fat-free mass composition and DXA lean mass composition corrected by limb length, which allows a surrogate measurement of muscle mass.

Change in Insulin sensitivity

Insulin resistance will be measured by HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) method. Insulin resistance reveals the dynamics between the participant's baseline (fasting) blood sugar and the responsive insulin levels. HOMA-IR healthy range: 1.0 (0.5-1.4), less than 1.0 means participant is insulin-sensitive which is optimal, above 1.9 indicates early insulin resistance, above 2.9 indicates significant insulin resistance.

Change in Fibroblast growth factor 21 (FGF21) levels

Fibroblast growth factor 21 (FGF21) is a hormone which regulate insulin signalling in response to nutritional status. Levels of FGF21 induced in response to low protein diet and fasting will be measured using enzyme-linked immunosorbent assay(ELISA) assay.

Change in Energy expenditure as measured by resting metabolic rate

Energy expenditure will be calculated from resting metabolic rate. Resting metabolic rate is the energy required by the body to perform the most basic functions when body is at rest.

Change in Muscle function as measured by jump maximal height

Jumping mechanography will be used to quantify muscle function. Jumping mechanography involves 3 supervised jumps on a force measurement platform. Analysis will be conducted on variables associated with the highest achieved jump height of the 3 trials. In Jumping mechanography, participants perform two-leg maximal countermovement jumps on a force plate (Leonardo, Novotec, Pforzheim, Germany). Maximal jump height(meter) will be calculated using Leonardo software.

Change in Muscle function as measured by jump velocity

Jumping mechanography will be used to quantify muscle function. Jumping mechanography involves 3 supervised jumps on a force measurement platform.Analysis will be conducted on variables associated with the highest achieved jump height of the 3 trials. In Jumping mechanography, participants perform two-leg maximal counter-movement jumps on a force plate (Leonardo, Novotec, Pforzheim, Germany). Jump velocity [meter/sec] will be calculated using Leonardo software.

Change in Muscle function as measured by relative power of jump

Jumping mechanography will be used to quantify muscle function. Jumping mechanography involves 3 supervised jumps on a force measurement platform.Analysis will be conducted on variables associated with the highest achieved jump height of the 3 trials. In Jumping mechanography, participants perform two-leg maximal countermovement jumps on a force plate (Leonardo, Novotec, Pforzheim, Germany). Relative power of jump [Watt/kg] will be calculated using Leonardo software.

Full Information

NCT ID

NCT04424537

First Posted

June 2, 2020

Last Updated

August 2, 2022

Sponsor

University of Wisconsin, Madison

1. Study Identification

Unique Protocol Identification Number

NCT04424537

Brief Title

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

Acronym

SOAR-2

Official Title

The Metabolic Response to Reduced Branched-chain Amino Acids in Humans 2

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Withdrawn due to lack of funding

Study Start Date

January 2024 (Anticipated)

Primary Completion Date

January 2028 (Anticipated)

Study Completion Date

January 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Wisconsin, Madison

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obesity, Diabetes

Keywords

Calorie restriction

7. Study Design

Primary Purpose

Basic Science

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Control

Arm Type

Placebo Comparator

Arm Description

Arm Title

Low protein(LP) diet

Arm Type

Active Comparator

Arm Description

Arm Title

Low branched-chain amino acids (BCAA)

Arm Type

Experimental

Arm Description

Intervention Type

Dietary Supplement

Intervention Name(s)

Control diet

Intervention Description

Meal replacement beverages made with whey protein

Intervention Type

Dietary Supplement

Intervention Name(s)

Low branched-chain amino acids(BCAA) diet

Intervention Description

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

Intervention Type

Dietary Supplement

Intervention Name(s)

Low protein diet

Intervention Description

meal replacement beverages(MRBs) containing low protein

Primary Outcome Measure Information:

Title

Change in weight

Description

Change in participant weight

Time Frame

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

Title

Change in fasting blood glucose level

Description

Change in the participant's fasting blood glucose level

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline, 60(-3 to +7)days

Title

Change in Insulin sensitivity

Description

Time Frame

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

Title

Change in Fibroblast growth factor 21 (FGF21) levels

Description

Time Frame

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

Title

Change in Energy expenditure as measured by resting metabolic rate

Description

Energy expenditure will be calculated from resting metabolic rate. Resting metabolic rate is the energy required by the body to perform the most basic functions when body is at rest.

Time Frame

Baseline, 60(-3 to +7)days

Title

Change in Muscle function as measured by jump maximal height

Description

Time Frame

Baseline, 60(-3 to +7)days

Title

Change in Muscle function as measured by jump velocity

Description

Jumping mechanography will be used to quantify muscle function. Jumping mechanography involves 3 supervised jumps on a force measurement platform.Analysis will be conducted on variables associated with the highest achieved jump height of the 3 trials. In Jumping mechanography, participants perform two-leg maximal counter-movement jumps on a force plate (Leonardo, Novotec, Pforzheim, Germany). Jump velocity [meter/sec] will be calculated using Leonardo software.

Time Frame

Baseline, 60(-3 to +7)days

Title

Change in Muscle function as measured by relative power of jump

Description

Jumping mechanography will be used to quantify muscle function. Jumping mechanography involves 3 supervised jumps on a force measurement platform.Analysis will be conducted on variables associated with the highest achieved jump height of the 3 trials. In Jumping mechanography, participants perform two-leg maximal countermovement jumps on a force plate (Leonardo, Novotec, Pforzheim, Germany). Relative power of jump [Watt/kg] will be calculated using Leonardo software.

Time Frame

Baseline, 60(-3 to +7)days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dawn B Davis, MD, PhD

Organizational Affiliation

University of Wisconsin, Madison

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Wisconsin-Madison School of Medicine and Public Health

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53726

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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