Changes in Cognition During a 24-h Simulated Military Operation

Changes in Cognition During a 24-h Simulated Military Operation (SUSOP). Influence of β-alanine Supplementation and Markers of Classical Monocyte Recruitment

Sustained military operations (SUSOPs) result in psychological stress and cognitive dysfunction, which may be related to the recruitment of classical monocytes into the brain.

Goals:

• To investigate the effect of sustained-release beta-alanine on changes in cognition and markers of immune cell recruitment during a 24-hour simulated military operation.
• To examine associations between changes cognition and changes in markers mediating immune cell recruitment.

Study Overview

• Status: Completed
• Conditions: Cognitive Impairment
• Intervention / Treatment: Dietary supplement: beta-alanine; Dietary supplement: placebo

Detailed Description

Sustained military operations (SUSOPs) expose soldiers to a multitude of stressors, including sustained physical activity, caloric deficit, and sleep deprivation. Several studies have shown that the combination of these factors result in psychological stress, which often leads to significant cognitive impairment.

Psychological stress has been shown to result in activation of neuroendocrine pathways that signal into the periphery and relay information from the brain to the immune system. This process is generally characterized by elevations of several key pro-inflammatory cytokines, chemokines, secondary messengers and reactive oxygen species. Notably, peripheral classical monocytes are reported to undergo recruitment to the brain during periods of psychological stress following priming by cytokines secreted from activated microglia.

Carnosine, an endogenous dipeptide consisting of beta-alanine and L-histidine, has been shown to inhibit the synthesis of inflammatory and oxidative mediators in microglia in vitro. Beta-alanine, which is the rate limiting amino acid in carnosine formation has been shown to increase carnosine concentrations in various regions of the brain in rodents which been associated with biochemical changes that resulted in favorable improvements in resilience to stress exposure. However, data on the effects of beta-alanine supplementation on cognition in humans is less clear. Further, the effect of beta-alanine supplementation on systemic and cellular mediators of monocyte recruitment has not been examined.

Goals:

• To investigate the effect of sustained-release beta-alanine on changes in psychological stress and cognition using Automated Neuropsychological Assessment Metric (ANAM) cognitive assessments during a 24-hour simulated military operation.
• To examine the effect of sustained-release beta-alanine on monocyte chemoattractant protein-1 (MCP-1), interleukin-8, Lymphocyte function-associated antigen-1 (CD11a), macrophage-1-antigen (CD11b) expression and C-C chemokine receptor 2 (CCR2) expression on neutrophils and classical monocytes during a 24-hour simulated military operation.
• To examine associations between MCP-1, interleukin-8, CD11a, CD11b, CCR2 and a composite measure of cognition derived from ANAM assessment scores during a 24-hour simulated military operation.

Method:

Double-blind placebo controlled trial compared the effect of supplementation with sustained release beta-alanine (12 grams per day) versus placebo (equivalent amount of rice powder) on cognition and monocyte responses during a 24-hour simulated military operation consisting of sleep-restriction, caloric restriction, and acute and sustained periods military specific physical activity.

Supplementation occurred over a period of 14 days prior to completion of the simulated military operation. ANAM tests were assessed and blood samples taken upon arrival to the lab for the 24 hour simulated operation (0 hours) and at 12, 18 and 24 hours during the SUSOP.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32816
      • Kinesiology Research Labs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Participants in this study will be males aged 18-35, preferably with military training or are current Reserve Officers' Training Corps cadets
• Free of any physical limitations (determined by medical and activity history questionnaire [MHQ] and the physical activity readiness questionnaire [PAR-Q+]).
• Participants will be required to be recreationally-active (defined according to American College of Sports Medicine standards of at least 150 minutes exercise per week).
• Participants must be willing abstain from dietary supplementation throughout the duration of the study.
• Participant understands the study procedures and signs forms providing informed consent to participate in the study.

Exclusion Criteria:

• Individual does not provide consent to participate in this study.
• Inability to perform physical exercise (determined by health and activity questionnaire [MHQ] and physical activity readiness questionnaire [PAR-Q+]). That is Answering "Yes" to any question on the PAR-Q+, or having a pre-existing condition such as musculoskeletal injury, back pain, chronic pain etc. that the investigative team perceives will prevent a participant from safely completing the protocol.
• Taking any other nutritional supplement or performance-enhancing drug (determined from health and activity questionnaire).
• Regularly taking any type of prescription or over-the-counter medication, or having any chronic illnesses, which require medical care.
• Inability to complete any of the exercise performance testing on the familiarization day.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Beta-alanine; 4 g by mouth, 3 times per day with regular meals for 14 days.	Dietary supplement: beta-alanine; beta-alanine tablet
Placebo Comparator: Placebo; 4 g by mouth, 3 times per day with regular meals for 14 days.	Dietary supplement: placebo; rice powder tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptoms checklist	monitor frequency and severity of subjective symptoms related to a broad spectrum of conditions. The participant is presented with 21 symptoms. The participant is required to rate each symptom (e.g. fatigue, headache, Nausea, numbness/tingling etc. on a scale from 0 (Not Present) to 6 (Severe)	Change from 0 at 12, 18 and 24 hours
COGcomp (composite measure of cognition)	Throughput (TP) scores from each of seven cognitive assessments administered as part of a battery of tests via Automated Neuropsychological Assessment Metrics (ANAM) computer software. Tests include: Simple reaction time; Code Substitution; Procedural Reaction Time; Mathematical processing; Matching to sample; Code substitution Delayed; Simple reaction time repeat	Change from 0 at 12, 18 and 24 hours
Monocyte chemoattractant protein-1 (MCP-1)	Serum concentrations of MCP-1	Change from 0 at 12, 18 and 24 hours
Macrophage-1-antigen (CD11b)	Surface expression of CD11b on classical monocytes and neutrophils	Change from 0 at 12, 18 and 24 hours
C-C chemokine receptor 2 (CCR2)	Surface expression of CCR2 on classical monocytes	Change from 0 at 12, 18 and 24 hours
Interleukin-8	Serum concentrations of interleukin-8	Change from 0 at 12, 18 and 24 hours
Lymphocyte function-associated antigen-1 (CD11a)	Surface expression of CD11a on classical monocytes and neutrophils	Change from 0 at 12, 18 and 24 hours

Collaborators and Investigators

• Sponsor: University of Central Florida
• Collaborators: National Strength and Conditioning Foundation
• Investigators: Principal Investigator: Adam J Wells, PhD, University of Central Florida

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2017
• Primary Completion (Actual): April 15, 2018
• Study Completion (Actual): April 15, 2018

Study Registration Dates

• First Submitted: January 29, 2020
• First Submitted That Met QC Criteria: January 30, 2020
• First Posted (Actual): January 31, 2020

Study Record Updates

• Last Update Posted (Actual): January 31, 2020
• Last Update Submitted That Met QC Criteria: January 30, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: beta-alanine; immune cells
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: SBE-17-13223

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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