Effects of Branch Chain Amino Acids on Glucose Tolerance in Obese Pre-Diabetic Subjects

Prediabetic State Clinical Trial

— BCAA  

Official title:

Effects of Branch Chain Amino Acids on Glucose Tolerance in Obese Pre-Diabetic Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02684565
• Other study ID #: IRB#15-001928
• Status: Completed
• Phase: N/A
• First received: February 9, 2016
• Last updated: February 8, 2018
• Start date: October 2016
• Est. completion date: February 2018

Study information

• Verified date: February 2018
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Branching chain amino acids (BCAA) have both beneficial and detrimental effects of on metabolism have been established and therefore warrants further investigation. In the preliminary study, the investigators found that BCAAs enhanced glucose metabolism in lean mice while they promoted glucose intolerance in obese mice. In lean mice, BCAAs decreased adiposity and enhanced glucose utilization and insulin sensitivity in different tissues. But in obese mice, BCAAs' effects were mediated by impaired insulin signaling in fat tissue.

This study will examine 10 obese subjects with pre-diabetes and examine the effects of taking BCAA supplement and will monitor the subjects blood glucose, insulin, triglyceride levels and will have an oral glucose tolerance test on repeated occasions to see if any changes are noted in their glucose regulation.

Description:

Branched-Chain Amino Acids (BCAAs, including leucine, isoleucine, and valine) regulate multiple cellular functions as nutrient signaling. For example, BCAAs regulate insulin and glucagon secretion and thus glucose metabolism1. BCAAs, especially leucine, is one key regulator of mTOR signaling, which is the central component of a complex signaling network of insulin signaling, cell growth, and proliferation. BCAAs also regulate protein synthesis and degradation in various tissues.

Increasing dietary uptake of BCAAs improved the parameters associated with obesity and T2DM, such as body composition and glycemia levels. However, these beneficial effects are not conclusive. Moreover, other studies have shown that circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents.

This is a 12-week, randomized, crossover study with 10 obese subjects with prediabetes. Subjects will be randomly assigned to take 20g BCAA or low-BCAA protein a day for 4 weeks, then switch to BCAA or low-BCAA protein for 4 weeks after a 2-week washout.

At baseline and weeks 4, 6 and 10 weeks glucose, insulin and triglyceride levels will be tested at time 0, 30 min, 60 min, and 120 min after 75 grams of glucose load. In addition to laboratory tests vital signs, weight and body composition will be done.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: February 2018
• Est. primary completion date: February 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Age 20-50 years of age at screen

2. BMI between 27 to 35

3. Fasting glucose level >100, but <126 mg/dL or HgbA1c >5.7% but < 6.4%

4. Waist circumference > 40 cm in men and >35 in women

5. Subjects must read and sign the Institutional Review Board-approved written informed consent prior to the initiation of any study specific procedures or enrollment. A subject will be excluded for any condition that might compromise the ability to give truly informed consent.

Exclusion Criteria:

1. Any subject with a history of diabetes mellitus on medications, or other serious medical condition, such as chronic hepatic or renal disease, bleeding disorder, congestive heart disease, cancer (except skin basal cell carcinoma ) chronic diarrhea disorders, myocardial infarction, coronary artery bypass graft, angioplasty within 6 months prior to screening, current diagnosis of uncontrolled hypertension (defined as systolic BP>160mmHg, diastolic BP>95mmHg), active or chronic gastrointestinal disorders, bulimia, anorexia, or endocrine diseases (except thyroid disease requiring medication) as indicated by medical history or routine physical examination.

2. Any subject with a screening laboratory value outside of the laboratory normal range that is considered clinically significant for study participation by the investigator.

3. Any subject who currently uses tobacco products.

4. Any history of gastrointestinal disease except for appendectomy.

5. Any antibiotic or laxative use during the 2 months before the study.

6. Any subject who is unable or unwilling to comply with the study protocol.

7. Any subject allergic to soy products.

Related Conditions & MeSH terms

• Prediabetic State

Intervention

Dietary Supplement:
• BCAA High Protein supplement
Subjects will be randomly assigned to take high BCAA or low-BCAA protein a day for 4 weeks, then switch to BCAA or low-BCAA protein for 4 weeks after a 2-week washout.
• BCAA Low Protein supplement
Subjects will be randomly assigned to take high BCAA or low-BCAA protein a day for 4 weeks, then switch to BCAA or low-BCAA protein for 4 weeks after a 2-week washout.

Locations

Country	Name	City	State
United States	University of California, Los Angeles	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (3)

Lynch CJ, Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol. 2014 Dec;10(12):723-36. doi: 10.1038/nrendo.2014.171. Epub 2014 Oct 7. Review. — View Citation

McCormack SE, Shaham O, McCarthy MA, Deik AA, Wang TJ, Gerszten RE, Clish CB, Mootha VK, Grinspoon SK, Fleischman A. Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents. Pediatr Obes. 2013 Feb;8(1):52-61. doi: 10.1111/j.2047-6310.2012.00087.x. Epub 2012 Sep 7. — View Citation

Pal S, Ellis V. The acute effects of four protein meals on insulin, glucose, appetite and energy intake in lean men. Br J Nutr. 2010 Oct;104(8):1241-8. doi: 10.1017/S0007114510001911. Epub 2010 May 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in glucose tolerance composition that Are Related to High protein BCAA Treatment	The major changes in glucose tolerance after taking supplement	Baseline to 4 weeks
Primary	Change in glucose tolerance and body composition that Are Related to Low protein BCAA Treatment	The major changes in glucose tolerance after taking supplement	Baseline to 4 weeks
Secondary	Change in glucose tolerance and body composition that Are Related to Low protein BCAA treament	Change in body composition after taking supplement	baseline to 4 weeks
Secondary	Change in glucose tolerance and body composition that Are Related to High Protein BCAA treament	Change in body composition after taking supplement	Baseline to 4 weeks