Pilot Study of BCAA on Sleep

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Sleep Disorder, Traumatic Brain Injury

Intervention / Treatment
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* Dietary Supplement: Branched Chain Amino Acids
* Dietary Supplement: Rice Protein
* Dietary Supplement: Microcrystalline Cellulose


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCAAs<br>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<br>* 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).<br>* Other names: BCAAs;|
| Placebo Comparator: Rice Protein<br>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<br>* 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).<br>|
| Placebo Comparator: Microcrystalline Cellulose<br>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<br>* 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).<br>|

What is the study measuring?
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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 |