Sleep RestrictionNCT03525184
Nutrition Intervention to Promote Immune Recovery From Sleep Restriction
A study testing Additional protein and multi-nutrient beverage in people with Sleep Restriction, run by United States Army Research Institute of Environmental Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Sleep Restriction
- What is being tested?
- Additional protein and multi-nutrient beverage
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Feb 2018to 10 Dec 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
U.S. Army Research Institute of Environmental Medicine
Natick, Massachusetts, 01760
About this study
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
- Being tested
- Additional protein and multi-nutrient beverage, Placebo beverage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Additional protein and multi-nutrient beverageOther
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).
Placebo beverageOther
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).
| Study group | Role | What they receive |
|---|---|---|
| Normal sleep | Placebo comparator | A normal sleep condition and the placebo treatment (0.9 g protein/kg body weight/day + placebo beverage; NS) Receives: 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), Receives: 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+). Receives: Other: Additional protein and multi-nutrient beverage |
What is being measured
The primary outcome is the main question the study is designed to answer.
Partial skin barrier restoration
Partial restoration of the skin barrier (i.e., to demonstrate initial phases of the wound healing process)
Measured: up to 10 days
Secondary outcomes (1)
Cytokine response of local wound fluid (e.g., IL-6, IL-8, TNF-a)
Immune response of blister fluid
Measured: 4, 7, 24, 48, 72 and 96-hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2018
- Study start12 Feb 2018
- Primary completion10 Dec 2019
- Study completion10 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sleep RestrictionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Model description
- Participants will undergo the study during normal sleep, sleep restriction without the multi-nutrient beverage and sleep restriction with the multi-nutrient beverage
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- United States Army Research Institute of Environmental Medicine
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, Tracey Smith, United States Army Research Institute of Environmental Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03525184
- Sponsor's protocol ID
- 17-27HC
- Status last verified
- Apr 2020
- First submitted
- 6 Feb 2018
- Last updated
- 27 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35285906Radcliffe 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.
PubMed 33940082
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nutrition Intervention to Promote Immune Recovery From Sleep Restriction
- ClinicalTrials.gov ID
- NCT03525184
- Acronym / sponsor ID
- 17-27HC
- Conditions
- Sleep Restriction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- United States Army Research Institute of Environmental MedicineUS federal agency
- Study start
- 12 Feb 2018 (actual)
- Primary completion
- 10 Dec 2019 (actual)
- Study completion
- 10 Dec 2019 (actual)
- First posted
- 15 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 3
- Model description
- Participants will undergo the study during normal sleep, sleep restriction without the multi-nutrient beverage and sleep restriction with the multi-nutrient beverage
| Arm | Type | Receives |
|---|---|---|
| Normal sleep | Placebo comparator | Other: Placebo beverageA normal sleep condition and the placebo treatment (0.9 g protein/kg body weight/day + placebo beverage; NS) |
| 72-h Sleep restriction with placebo beverage | Placebo comparator | Other: Placebo beverageSleep 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), |
| 72-h Sleep restriction with multi-nutrient beverage | Experimental | Other: Additional protein and multi-nutrient beverageSleep 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+). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (15 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Additional protein and multi-nutrient beverageDuring 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). | Other | 72-h Sleep restriction with multi-nutrient beverage |
| Placebo beverageThe 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). | Other | 72-h Sleep restriction with placebo beverage, Normal sleep |
Primary outcome
Partial skin barrier restoration
Time frame: up to 10 days
Partial restoration of the skin barrier (i.e., to demonstrate initial phases of the wound healing process)
1 secondary outcome
Cytokine response of local wound fluid (e.g., IL-6, IL-8, TNF-a)
Time frame: 4, 7, 24, 48, 72 and 96-hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2020.
- Derived from this study: PubMed 35285906Smith 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.
- Derived from this study: PubMed 33940082Radcliffe 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Additional protein and multi-nutrient beverage in people with Sleep Restriction, run by United States Army Research Institute of Environmental Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Partial skin barrier restoration (time frame: up to 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03525184, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2020.