Clinical trial NCT03990909: Pilot Study of BCAA on Sleep
Official title: A Pilot Study of Dietary Supplementation With Branched Chain Amino Acids on Sleep
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sleep Disorder
Traumatic Brain Injury
Lead sponsor: Portland VA Medical Center
Sponsor class: FED
First posted: 2019-06-19
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Recruitment and retention rates
timeFrame: 5 weeks
measure: Rates of adherence and treatment fidelity
timeFrame: 5 weeks
measure: Assessment process and patient acceptability
timeFrame: 5 weeks
Secondary outcomes:
measure: Change in Insomnia Severity Index (ISI)
timeFrame: Baseline; after 3 weeks of intervention
Other outcomes:
Locations:
city: Portland
country: United States
facility: VA Portland Health Care System
state: Oregon
Study officials:
affiliation: Portland VA Medical Center
name: Miranda M Lim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.