The Metabolic Response to Reduced Branched-chain Amino Acids in Humans (SOAR)

Branched-chain amino acids (BCAAs) are essential nutrients that the body obtains from proteins found in food, especially meat, diary products, and legumes. Data from rodent studies suggest that reduction of dietary BCAAs will promote fat mass loss and improved control of blood glucose. The purpose of this study is to test if reduction of dietary BCAAs without reducing calorie intake will lead to similar metabolic benefits in humans. Here the investigators test the feasibility of reducing dietary BCAAs using BCAA-free meal replacement beverages for two months.

Study Overview

• Status: Completed
• Conditions: Obesity; Diabetes; Insulin Resistance
• Intervention / Treatment: Other: Whey protein powder; Other: BCAD2

Detailed Description

This study, which will be completed over three months, involves replacing two meals a day with meal replacement beverages for two months, with a one month follow-up visit. These beverages will be made up by subjects using either a complete protein powder or BCAD2, a BCAA-free medical food. Participants will complete food diaries at baseline and at one month intervals during the study, and compliance will be assessed via food diaries, weekly telephone contact, and measuring returned food powder.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53726
      • University of Wisconsin-Madison School of Medicine and Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Male between the age of 35 - 65
2. BMI between 28 - 35 (mildly obese/overweight)
3. Fasting glucose level of 101 - 125 mg/dL
4. Able and willing to give written informed consent
5. Stable weight (within 5 lbs. for at least 3 months)
6. Not taking (or willing to cease taking) over the counter vitamin/mineral supplements
7. Not planning to begin an exercise or diet program

Exclusion Criteria:

1. Female
2. Outside required age range of 35 - 65
3. BMI not within range of 28 - 35
4. Fasting glucose not within range of 101 - 125 mg/dL
5. Use of prescription medications for diabetes or weight-loss
6. Use of and unwillingness to discontinue over the counter supplements (e.g. cinnamon, chromium, protein powders) or weight loss beverage or meal plans (e.g. SlimFast or Jenny Craig).
7. Low baseline albumin or pre-albumin levels (below normal reference range)
8. Significant anemia (Hemoglobin < 11 g/dL)
9. Known bleeding disorder or platelet dysfunction
10. Already eating a low protein diet (less than 14% total caloric intake from protein), as calculated from food diaries provided by subjects
11. 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.
12. Significant co-morbidities (including kidney disease, liver disease, GI disease, cardiovascular disease, respiratory disease, malnutrition, substance abuse, psychiatric disease, or a diagnosed eating disorder).
13. Planned smoking cessation or attempt at smoking cessation during study period
14. Inability to tolerate meal replacement beverages due to palatability
15. Recent weight loss (> 5 lbs within 3 months).
16. Bariatric surgery, gastric banding or liposuction
17. Current or past (within 1 year) use of illicit drugs
18. Claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Whey protein powder; Participants in the Placebo Arm will replace two-thirds of participants dietary protein intake with meal replacement beverages utilizing a complete protein powder.	Other: Whey protein powder; Participants in the Control Arm will replace two-thirds of participants dietary protein intake with a commercially available whey protein powder.
Experimental: Experimental; Participants in the Experimental Arm will replace two-thirds of participants dietary protein intake with BCAD2 (Mead Johnson), a BCAA-free medical food.	Other: BCAD2; Participants in the Experimental Arm will replace two-thirds of participants dietary protein intake with BCAD2 (Mead Johnson), a BCAA-free medical food.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of BCAA intake	The principle outcome of this study is to determine if replacing 2/3rds of the subjects baseline protein intake with BCAA-free meal replacement beverages are a feasible method of selectively reducing BCAA consumption. Our principle outcome is to reduce BCAA intake by 50% or more in the Experimental Arm (BCAD2) of the study as compared to baseline intake.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	Weight in kg	3 months
Fat mass	Fat mass in kg	3 months
BMI	Weight in kg and height in meters will be combined to report BMI in kg/m^2	3 months
Resting metabolic rate	Resting metabolic rate in kcal/hour	3 months
Fasting blood glucose	Fasting blood glucose in mg/dL	3 months
Insulin	Insulin in ng/dL	3 months
HbA1c	HbA1c in mmol/mol	3 months
Glucose tolerance	Area under the curve in mg/dL/min	3 months

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Dudley W Lamming, PhD, UW-Madison; Principal Investigator: Dawn B Davis, MD, PhD, UW-Madison

Publications and helpful links

General Publications

• Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, Cava E, Spelta F, Tosti V, Syed FA, Baar EL, Veronese N, Cottrell SE, Fenske RJ, Bertozzi B, Brar HK, Pietka T, Bullock AD, Figenshau RS, Andriole GL, Merrins MJ, Alexander CM, Kimple ME, Lamming DW. Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health. Cell Rep. 2016 Jul 12;16(2):520-530. doi: 10.1016/j.celrep.2016.05.092. Epub 2016 Jun 23.

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2017
• Primary Completion (Actual): July 16, 2021
• Study Completion (Actual): July 16, 2021

Study Registration Dates

• First Submitted: May 16, 2017
• First Submitted That Met QC Criteria: August 3, 2017
• First Posted (Actual): August 4, 2017

Study Record Updates

• Last Update Posted (Actual): July 30, 2021
• Last Update Submitted That Met QC Criteria: July 28, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: 2017-0099; Protocol Version 2/23/2021 (Other Identifier: UW Madison); A534245 (Other Identifier: UW Madison); SMPH\MEDICINE\ENDOCRINOL (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No