Pilot Study of BCAA on Sleep

A Pilot Study of Dietary Supplementation With Branched Chain Amino Acids on Sleep

Individuals will be recruited from the VA Portland Health Care System and the community affiliated with Oregon Health & Science University. Traumatic brain injury status will be assessed as a contributing factor. Subjects will be randomized to one of 3 groups (BCAA or one of 2 placebo conditions) and instructed to consume study product twice daily for 21 days. Self-report questionnaires, wrist actigraphy, pressure pain testing, and cognitive function will be assessed pre and post the experimental period.

Study Overview

• Status: Recruiting
• Conditions: Sleep Disorder; Traumatic Brain Injury
• Intervention / Treatment: Dietary supplement: Branched Chain Amino Acids; Dietary supplement: Rice Protein; Dietary supplement: Microcrystalline Cellulose

Detailed Description

The goal of this proposal is to explore the feasibility of, and potential for, dietary supplementation with branched chain amino acids (BCAAs) to effect sleep quality and cognitive function in Veterans. The BCAAs (Leucine, Isoleucine, and Valine) cannot be synthesized endogenously (i.e., they must be obtained through the diet) and are the precursors to >50% of de novo glutamate and GABA synthesis in the brain, which are the primary excitatory and inhibitory neurotransmitters, respectively. Preclinical evidence strongly suggests that dietary BCAA supplementation restores normal sleep-wake patterns and cognitive function following TBI through a restoration in the global cortical excitation:inhibition ratio. BCAA supplementation has been studied extensively in healthy humans and in a variety of disease states, including following TBI, but not yet in Veterans in the chronic phase of recovery from TBI. BCAAs are a commercially available dietary supplement and very well tolerated with minimal side-effects.

Subjects will be randomized in a double-blind fashion through the VA Research Pharmacy to one of three groups: 1) BCAA; 60 g/day in two 30 g doses, 2) rice protein; 60 g/day in two 30 g doses, and 3) placebo; 60 g microcrystalline cellulose in two 30 g doses. BCAA and placebo will be prepared by the VA Research Pharmacy and dispensed in a blinded fashion to Veterans after demonstrating informed consent. Following a ~4-week period of baseline, Veterans will be instructed to consume study product after waking and ~6 hours later, on an empty stomach for a period of up to 21-days. Self-report questionnaires assessing sleep quality, cognitive function, trauma-related symptom severity, and other measures of mental and physical well-being will be administered before and after the experimental period. Wrist actigraphy will be continuously collected over the baseline and the experimental period. Cognitive function will be assessed before and after the experimental period using an established battery of neuropsychological tests (i.e., selected tests from WAIS, D-KEFS, HVLT, COWAT, among others. Pressure pain testing will be conducted before and after the experimental period.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Miranda M Lim, MD, PhD; Phone Number: Ext. 57404 503-220-8262; Email: lmir@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • VA Portland Health Care System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Veteran
• English Speaking
• Accessible via phone
• Sleep problems

Exclusion Criteria:

• Decisional impairment
• Nickel allergy
• Maple syrup urine disease or family history of disease
• Allergy to sucralose
• Currently taking BCAAs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCAAs; 60 grams of BCAA (2:1:1 ratio of Leucine:Isoleucine:Valine) consumed in two doses (30 grams each) mixed into 20 oz of water for up to 21 days (42 total drinks).	Dietary supplement: Branched Chain Amino Acids; 60 grams of BCAA (2:1:1 ratio of Leucine:Isoleucine:Valine) consumed in two doses (30 grams each) mixed into 20 oz of water for up to21days (42 total drinks).; Other Names: BCAAs
Placebo Comparator: Rice Protein; Rice protein control group: 60 grams of rice protein consumed in two doses (30 grams each) mixed into 20 oz of water for up to 21 days (42 total drinks).	Dietary supplement: Rice Protein; 60 grams of rice protein consumed in two doses (30 grams each) mixed into 20 oz of water for up to 21days (42 total drinks).
Placebo Comparator: Microcrystalline Cellulose; Placebo control group: 60 grams of microcrystalline cellulose, consumed in two doses (30 grams each) mixed into 20 oz of water for up to 21 days (42 total drinks).	Dietary supplement: Microcrystalline Cellulose; 60 grams of microcrystalline cellulose, consumed in two doses (30 grams each) mixed into 20 oz of water for up to 21days (42 total drinks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment and retention rates	Number enrolled per month, proportion who complete the protocol	5 weeks
Rates of adherence and treatment fidelity	Proportion of subjects consuming full doses	5 weeks
Assessment process and patient acceptability	Proportion of questionnaires properly completed, actiwatches properly worn, and patient acceptance of protocol	5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Insomnia Severity Index (ISI)	Measures self-reported insomnia severity; total score range = 0-28 (higher total score = worse insomnia)	Baseline; after 3 weeks of intervention

Collaborators and Investigators

• Sponsor: Portland VA Medical Center

Publications and helpful links

General Publications

• Elliott JE, Keil AT, Mithani S, Gill JM, O'Neil ME, Cohen AS, Lim MM. Dietary Supplementation With Branched Chain Amino Acids to Improve Sleep in Veterans With Traumatic Brain Injury: A Randomized Double-Blind Placebo-Controlled Pilot and Feasibility Trial. Front Syst Neurosci. 2022 May 4;16:854874. doi: 10.3389/fnsys.2022.854874. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): August 1, 2025

Study Registration Dates

• First Submitted: June 17, 2019
• First Submitted That Met QC Criteria: June 17, 2019
• First Posted (Actual): June 19, 2019

Study Record Updates

• Last Update Posted (Actual): April 5, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Sleep Wake Disorders; Brain Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: MIRB 4312

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All non-identifiable data will be made available to qualified researchers on request to the study PI.
• IPD Sharing Time Frame: Information will be sent as soon as is practical and will be available as long as the PI is available.
• IPD Sharing Access Criteria: Legitimate research agenda, including but not limited to request to double-check presented or published results and novel analyses.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

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