Clinical trial NCT04424537: SOAR-2: Intervening in Obesity Through Reduction of Dietary Branched Chain Amino Acids
Official title: The Metabolic Response to Reduced Branched-chain Amino Acids in Humans 2
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Obesity
Diabetes
Keywords: Calorie restriction
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2020-06-11
Enrollment: 0
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Change in weight
timeFrame: Baseline, 30 (±7)days, 60(-3 to +7)days, 134(+7) days
measure: Change in fasting blood glucose level
timeFrame: Baseline, 30 (±7)days, 60(-3 to +7)days, 134(+7) days
Secondary outcomes:
measure: Change in the body composition (adipose mass) as measured by DXA/BIS
timeFrame: Baseline, 60(-3 to +7)days
measure: Change in Insulin sensitivity
timeFrame: Baseline, 30 (±7)days, 60(-3 to +7)days, 134(+7) days
measure: Change in Fibroblast growth factor 21 (FGF21) levels
timeFrame: Baseline, 30 (±7)days, 60(-3 to +7)days
measure: Change in Energy expenditure as measured by resting metabolic rate
timeFrame: Baseline, 60(-3 to +7)days
measure: Change in Muscle function as measured by jump maximal height
timeFrame: Baseline, 60(-3 to +7)days
measure: Change in Muscle function as measured by jump velocity
timeFrame: Baseline, 60(-3 to +7)days
measure: Change in Muscle function as measured by relative power of jump
timeFrame: Baseline, 60(-3 to +7)days
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin-Madison School of Medicine and Public Health
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Dawn B Davis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: