Nutrition Intervention to Promote Immune Recovery From Sleep Restriction

NCT03525184 | Completed

• 1 other identifier: 17-27HC
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Physical and psychological stress on Warfighters during training and operational missions can suppress immune responsiveness. Skin wound models can be used to detect changes in immune function. Investigators have recently demonstrated that relatively modest sleep disruption degrades immune response at the site of the disrupted skin barrier and delays the initial restoration of the skin barrier. Provision of additional protein and a multi-nutrient beverage during and after sleep restriction seems to mitigate decrements in local immune function, without producing detectable effects on initial restoration of the skin barrier. However, the prior work used a parallel-group study design and inter-subject variability may have made it more difficult to detect significant differences in skin barrier restoration between participants receiving the nutrition intervention versus those receiving the placebo. Therefore, the purpose of the proposed cross-over study is to test the efficacy of a multi-nutrient beverage and additional protein (1.5 g protein per kg body weight versus 0.9 g protein per kg body weight) on immune function and the initial restoration of the skin barrier consequent to an operational stressor (i.e., 72-h sleep restriction). The effect of sleep restriction on a friend-foe marksmanship task, flow state, and measures of cognitive and neuromotor performance, will be investigated as a sub-study (Appendix A). Additionally, the effects of sleep restriction on appetite physiology, eating behaviors and intestinal permeability will be tested. Research will be conducted in a laboratory environment using male and female Soldiers from the human research participant detachment (NSRDEC), or Soldiers or civilians at NSRDEC and/or USARIEM. Participants in the study described herein (n = 20) will be exposed, in a single-blind, cross-over design to a \~72 hour normal sleep control phase, and to 2 periods of \~72 hours of sleep restriction (monitored in laboratory with \~2-h sleep per night) during which time eight blisters will be induced via suction on participant's forearm and the top layer of blisters will be removed to reveal the dermal layer of skin. In the normal sleep trial, participants will consume \~0.9 g protein per kg body weight per day and a placebo beverage during (3 days). In the first sleep restriction trial, participants will consume \~0.9 g protein per kg body weight per day and a placebo beverage during (3 days) and after (5 days) sleep restriction; and, in the second sleep restriction trial (after at least two weeks wash-out) participants will instead consume \~1.5 g protein per kg body weight and a multi-nutrient beverage (arginine: 20 g·d-1, glutamine: 30 g·d-1, zinc sulfate: 24 mg·d-1, vitamin C: 400 mg·d-1, vitamin D3: 800 IU·d-1 and omega-3 fatty acids: 1 g·d-1). Outcome measures include immune function (e.g., circulating markers of inflammation, cytokines at the blister site, and secretory immunoglobin A), skin barrier restoration time (by transepidermal water loss), subjective appetite ratings, appetite-mediating hormone concentrations, food preferences and cravings, gut microbiota composition, and intestinal permeability. Findings from this study will determine if a nutritional intervention attenuates the loss of immune responsiveness to a military relevant stressor (i.e., sleep restriction), and will determine the effects of acute sleep restriction on appetite, gut microbiota composition, and intestinal permeability.

Conditions

Sleep Restriction

Outcome Measures

Primary Outcomes (1)

• Partial skin barrier restoration

  Partial restoration of the skin barrier (i.e., to demonstrate initial phases of the wound healing process)

  up to 10 days

Secondary Outcomes (1)

• Cytokine response of local wound fluid (e.g., IL-6, IL-8, TNF-a)

  4, 7, 24, 48, 72 and 96-hours

Other Outcomes (6)

• Lactulose:mannitol ratio of urine

  5-h

• Appetite ratings

  Throughout study participation (~68 days)

• Energy consumption

  Throughout study participation (~68 days)

Study Arms (3)

Normal sleep

PLACEBO COMPARATOR

A normal sleep condition and the placebo treatment (0.9 g protein/kg body weight/day + placebo beverage; NS)

Other: Placebo beverage

72-h Sleep restriction with placebo beverage

PLACEBO COMPARATOR

Sleep restriction (72-h with 2-h of sleep per night) and the placebo treatment (0.9 g protein/kg body weight/day + placebo beverage; SR),

Other: Placebo beverage

72-h Sleep restriction with multi-nutrient beverage

EXPERIMENTAL

Sleep restriction (72-h with 2-h of sleep per night) and the experimental treatment (1.5 g protein/kg body weight/day + multi-nutrient beverage; SR+).

Other: Additional protein and multi-nutrient beverage

Interventions

Additional protein and multi-nutrient beverage OTHER

During SR+, participants will consume a multi-nutrient beverage and additional protein (\~1.5 grams·kg-1 body weight·day-1 versus the lower end of MDRI of \~0.9 grams·kg-1 body weight·day-1) during and after the period of sleep restriction. The multi-nutrient beverage contains arginine, glutamine, vits C \& D, zinc and omega-3 fatty acids (DHA and EPA).

72-h Sleep restriction with multi-nutrient beverage

Placebo beverage OTHER

The placebo beverage (NS and SR) will be composed of a commercially-available artificially sweetened (e.g., containing aspartame, splenda or another artificial sweetener) beverage powder base and grapefruit extract (i.e., naringen) and/or quinine (i.e., a common ingredient found in tonic water).

72-h Sleep restriction with placebo beverage; Normal sleep

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Active duty military personnel and civilians with prior rifle marksmanship experience, and who sleep between 7 and 9 hours per night at least 5 days per week, and are between the ages of 18 and 45 will be invited to participate in this study.

You may not qualify if:

• Potential participants will be excluded from participation if they:
• are under the age of 18 or over the age of 45;
• have a tattoo on either forearm; are taking nonsteroidal anti-inflammatory drugs (e.g., Advil), aspirin, lipid-lowering drugs or corticosteroids; pregnant or lactating; are immune-compromised (e.g., chemotherapy or radiation treatment);
• are suffering from an autoimmune disease (e.g., lupus);
• recovering from a surgery within the past 6 months; have an injury that will prevent physical activity;
• have a recent eye injury (within the past 6 months) or have had eye surgery within the past year, have doctor-diagnosed dry eye syndrome;
• have a history of cardiovascular or metabolic disease; are suffering from sleep apnea; have a history of psychiatric disorder requiring hospitalization or have taken psychiatric medication (e.g., anti-depressants or anti-anxiety medication) within the past three years for any length of time;
• are suffering from any neurological disorder (e.g., epilepsy or other seizure disorder, narcolepsy or other sleep disorders, or multiple sclerosis);
• have a history of gastrointestinal disease (such as celiac disease, irritable bowel syndrome, colitis, and Crohn's disease), have taken oral antibiotics within the 3 months prior to study participation;
• and have a Body Mass Index (BMI) ≥ 30;
• have speech, facial or muscle disorder or injuries preventing them from producing a normal range of hand or finger motion.
• Participants will be asked not to sign the consent form if they regularly (more than 2 days per week) sleep less than 7 hours or more than 9 hours per night; or, take a nap 3 or more days per week.
• Potential participants will also be excluded from participation if they will feel uncomfortable handling a weapon, shooting at silhouette targets, have an injury that will impair firing a rifle, have ever been diagnosed with post-traumatic stress disorder, are unable to distinguish the color "red" from the color "black", or have a bowel movement less frequently than every-other-day.
• Potential participants also must agree to abstain from smoking, chewing or vaping tobacco or nicotine-containing products during the live-in portions of the study.
• Participants must be able to speak and read English fluently and will require a general medical clearance.

Sponsors & Collaborators

• United States Army Research Institute of Environmental Medicine: lead

Study Sites (1)

U.S. Army Research Institute of Environmental Medicine

Natick, Massachusetts, 01760, United States

Location

Related Publications (2)

• Smith TJ, Wilson M, Whitney C, Fagnant H, Neumeier WH, Smith C, Heaton KJ, Cho E, Spielmann G, Walsh NP, Karl JP. Supplemental Protein and a Multinutrient Beverage Speed Wound Healing after Acute Sleep Restriction in Healthy Adults. J Nutr. 2022 Jun 9;152(6):1560-1573. doi: 10.1093/jn/nxac064.

  PMID: 35285906 DERIVED

• Radcliffe PN, Whitney CC, Fagnant HS, Wilson MA, Finlayson G, Smith TJ, Karl JP. Severe sleep restriction suppresses appetite independent of effects on appetite regulating hormones in healthy young men without obesity. Physiol Behav. 2021 Aug 1;237:113438. doi: 10.1016/j.physbeh.2021.113438. Epub 2021 Apr 30.

  PMID: 33940082 DERIVED

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Nutrition Scientist

Model Details: Participants will undergo the study during normal sleep, sleep restriction without the multi-nutrient beverage and sleep restriction with the multi-nutrient beverage

Study Record Dates

• First Submitted: February 6, 2018
• First Posted: May 15, 2018
• Study Start: February 12, 2018
• Primary Completion: December 10, 2019
• Study Completion: December 10, 2019
• Last Updated: April 27, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)