- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04111263
Gut-microbiota Targeted Nutritional Intervention for Gut Barrier Integrity at High Altitude
December 20, 2022 updated by: United States Army Research Institute of Environmental Medicine
Efficacy of a Gut-microbiota Targeted Nutritional Intervention for Promoting Gut Barrier Integrity During Short-term Exposure to Hypobaric Hypoxia.
The aim of this randomized, crossover clinical trial is to determine the efficacy of a gut microbiota-targeted nutritional intervention containing a blend of fermentable fibers and polyphenols (FP) for mitigating increases in GI permeability, and decrements in immune function and neuropsychologic performance following rapid ascent to simulated high altitude.
Fifteen healthy young adults will participate in each of three study phases that include a 14-day supplementation period in which participants will consume 1 of 2 supplement bars: placebo (PL, will be consumed during 2 phases) and FP supplementation (will be consumed during one phase only).
During the final 2-d of each phase, participants will live in a hypobaric chamber under sea level or high altitude conditions.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
The collection of microbes inhabiting the human gastrointestinal (GI) tract, known as the gut microbiota, is increasingly recognized as a mediator of GI, immunologic, and neuropsychologic responses to various environmental and physiologic stressors.
The hypobaric hypoxia characteristic of high altitude environments is a stressor that has recently been associated with increased GI permeability, and which has been shown to cause decrements in immune, neuropsychological and physical function.
To what extent modulation of the human gut microbiota can mitigate these responses during high altitude exposure is undetermined.
The aim of this randomized, crossover clinical trial is to determine the efficacy of a gut microbiota-targeted nutritional intervention containing a blend of fermentable fibers and polyphenols (FP) for mitigating increases in GI permeability, and decrements in immune function and neuropsychologic performance following rapid ascent to simulated high altitude.
Fifteen healthy young adults will participate in each of three study phases in random order.
Each phase will include a 14-day supplementation period in which participants will consume 1 of 2 supplement bars: placebo (PL, will be consumed during 2 phases) and FP supplementation (will be consumed during one phase only).
During the final 2-d of each phase, participants will live in a hypobaric chamber.
During one phase the chamber environment will mimic low-altitude conditions (SHAM).
During two phases the chamber environment will mimic the barometric pressure at Pike's Peak CO (460 mmHg; HA).
Study Type
Interventional
Enrollment (Actual)
33
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Massachusetts
-
Natick, Massachusetts, United States, 01760
- USARIEM
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
17 years to 39 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion criteria:
- Men and women aged 18 - 39 years (active duty personnel who are 17 yr of age will also be allowed to participate)
- In good health
- Physically active
- For active duty, passed most recent body composition assessment; for civilians, body mass index (BMI) ≤ 30.0 kg/m2.
- Self-reports having a bowel movement at least as frequently as every-other-day
- Self-reports normal vision (with or without glasses) and hearing
Exclusion Criteria:
- Born at altitudes greater than 2,100 m (~7,000 feet)
- Living in areas that are more than 1,200 m (~4,000 feet), or have traveled to areas that are more than 1,200 m for five days or more within the last 2 mo
- Pregnant, expecting to become pregnant during study, or breastfeeding
Any of the following medical conditions:
- Musculoskeletal injuries that compromise exercise capability
- Metabolic or cardiovascular abnormalities (e.g., kidney disease, diabetes, cardiovascular disease, etc.)
- Suspected or known strictures, fistulas, or physiological/mechanical GI obstruction
- Evidence of apnea or other sleeping disorders
- Evidence of prior high altitude pulmonary or cerebral edema diagnosis
- Disease of the GI tract including, but not limited to diverticulitis, inflammatory bowel disease, peptic ulcer disease, Crohn's disease, ulcerative colitis
- Anemia or Sickle Cell Anemia/Trait
- Alcoholism or other substance abuse issues
- History of gastric bezoar
- Swallowing disorders; severe dysphagia to food or pills
- Implanted or portable electro-mechanical medical devices
- Allergy to skin adhesive
- Past GI surgery
- Colonoscopy within 3 months of study participation
- Taking prescription medications other than a contraceptive (unless approved by Medical Office and study PI)
- Regular use of over-the-counter medications (including antacids, laxatives, stool softeners, and anti-diarrheals) unless approved by Medical Office and study PI
- Any use of antibiotics, except topical antibiotics, within 3 months of study participation
- Not willing to refrain from using non-steroidal anti-inflammatory medications (NSAIDs) or antihistamine during the study
- Not willing to stop consumption of prebiotic- or probiotic-containing supplements (e.g.,VSL#3, PRO-15, etc.), or other dietary supplements at least 2 weeks before and throughout study participation
- Not willing to stop consumption of probiotic-containing foods (e.g., yogurt, etc.) during study participation.
- Not willing to refrain from smoking any nicotine product (includes e-cigarettes), vaping, and chewing tobacco during controlled-diet periods.
- Not willing to abstain from caffeine and alcohol during controlled-diet periods.
- Allergies, intolerances, unwillingness or inability to eat provided foods and beverages
- Following vegetarian/vegan diet
- Unable to regularly sleep for 7-10 hr/night
- Any previous blood donation, within 8 weeks of the first blood draw of the study, of a volume that when combined with the amount of blood to be collected during the study would exceed 550 mL
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Sham Comparator: PL+SHAM
Placebo intervention + sea level exposure
|
Matched placebo
Sea level environment in altitude chamber
|
Placebo Comparator: PL+HA
Placebo intervention + high altitude exposure
|
Matched placebo
Simulated high altitude in altitude chamber using hypobaric hypoxia
|
Experimental: FP+HA
Fiber and polyphenol supplementation + high altitude exposure
|
Simulated high altitude in altitude chamber using hypobaric hypoxia
Fiber and polyphenol blend
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Difference in intestinal permeability
Time Frame: Study days 20, 40 and 60
|
Intestinal permeability measured by the ratio of the urinary excretion of sucralose and erythrirol
|
Study days 20, 40 and 60
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Difference in lipopolysaccharide binding protein concentrations
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Fasting serum lipopolysaccharide binding protein concentration
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in zonulin concentrations
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Fasting serum zonulin concentration
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in glucagon-like peptide-2 concentrations
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Fasting serum glucagon-like peptide-2 concentration
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in intestinal fatty acid binding protein concentrations
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Fasting and post-exercise serum intestinal fatty acid binding protein concentration
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in claudin-3 concentrations
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Fasting and post-exercise serum claudin-3 concentration
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in S100B concentrations
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Fasting and post-exercise serum S100B concentration
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in systemic inflammation
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Fasting serum interleukin (IL) IL-6, IL-8, IL-10, IL-17, IL-1β, IL-1ra, tumor necrosis factor-α, interferon-γ concentrations
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in intestinal inflammation
Time Frame: Study days 6, 18, 21, 23, 27, 39, 42, 44, 48, 60, 63, 65
|
Fecal calprotectin concentration
|
Study days 6, 18, 21, 23, 27, 39, 42, 44, 48, 60, 63, 65
|
Difference in glucose concentrations
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Fasting and post-exercise serum glucose concentrations
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in insulin concentrations
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Fasting and post-exercise serum insulin concentrations
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in lactate concentrations
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Fasting and post-exercise serum lactate concentrations
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in glycerol concentrations
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Fasting and post-exercise serum glycerol concentrations
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in cortisol concentrations
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Fasting and post-exercise serum cortisol concentrations
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in bone specific alkaline phosphatase concentrations
Time Frame: Study days 20, 41, 62
|
Fasting serum bone specific alkaline phosphatase concentration
|
Study days 20, 41, 62
|
Difference in carboxy-terminal collagen crosslinks concentrations
Time Frame: Study days 20, 41, 62
|
Fasting serum carboxy-terminal collagen crosslinks concentration
|
Study days 20, 41, 62
|
Difference in tartrate resistant acid phosphatase concentrations
Time Frame: Study days 20, 41, 62
|
Fasting serum tartrate resistant acid phosphatase concentration
|
Study days 20, 41, 62
|
Difference in procollagen type 1 N-terminal propeptide concentrations
Time Frame: Study days 20, 41, 62
|
Fasting serum procollagen type 1 N-terminal propeptide concentration
|
Study days 20, 41, 62
|
Difference in osteocalcin concentrations
Time Frame: Study days 20, 41, 62
|
Fasting serum osteocalcin concentration
|
Study days 20, 41, 62
|
Difference in secretory immunoglobulin A concentrations
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Secretory immunoglobulin A concentrations in tear fluid and saliva
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in immune cell phenotypes
Time Frame: Study days 21, 42, 63
|
Immune cell phenotype by flow cytometry
|
Study days 21, 42, 63
|
Difference in T-cell simulated cytokine production
Time Frame: Study days 21, 42, 63
|
T-cell simulated cytokine production by cell culture and flow cytometry
|
Study days 21, 42, 63
|
Difference in natural killer-cell cytotoxicity
Time Frame: Study days 21, 42, 63
|
Natural killer-cell cytotoxicity by cell culture and flow cytometry
|
Study days 21, 42, 63
|
Difference in development of acute mountain sickness
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Environmental Symptoms Questionnaire-short form.
Acute Mountain Sickness will be measured multiple times daily using the Lake Louise scoring system wherein higher scores indicate more severe symptoms.
AMS severity cutoffs will use mild (0.7-1.53), moderate (1.53-2.63),
severe >=2.63
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in gastrointestinal symptoms; quality of life
Time Frame: Study weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9
|
Gastrointestinal symptoms measure by modified version of the gastrointestinal quality of life index wherein lower scores indicate more severe symptoms.
|
Study weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9
|
Difference in gastrointestinal symptoms; irritable bowel syndrome
Time Frame: Study weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9
|
Gastrointestinal symptoms measure by modified version of the irritable bowel syndrome symptom severity scale score wherein higher scores indicate more severe symptoms.
Scored on scale of 0-500; symptom severity scored as mild (75-174), moderate (175-300), severe (>300).
|
Study weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9
|
Difference in appetite
Time Frame: Study weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9
|
Hunger, fullness, desire to eat, and prospective consumption measured by 100 mm visual analog scale.
Scored from 0-100 with higher scores indicating greater sensation.
|
Study weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9
|
Difference in changes in mood state
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Measured by Profile of Mood States Questionnaire; a 65-item inventory of self-reported mood states which factor into six mood sub-scales (tension/anxiety (0-36), depression/dejection (0-60), anger/hostility (0-48), vigor/activity (0-32), fatigue/inertia (0-28), confusion/bewilderment (0-28), and total mood disturbance (0-200) wherein higher scores indicate greater mood state.
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in changes in feeling
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Measured by Feeling Scale; a one-item inventory measuring the extent to which participants feel pleasant or unpleasant.
Higher scores indicate more unpleasant feeling.
Scored from -5 (very bad) to 5 (very good)
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in changes arousal
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Measured by Felt Arousal Scale; a one-item inventory measuring the extent to which participants feel aroused.
Higher scores indicate greater arousal (low=1 to high =6).
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in willingness to take risks
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Measured by Evaluation of Risks Questionnaire; a 24-item questionnaire providing scores on five scales: self-control, danger seeking, energy, impulsivity, and invincibility.
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in risk taking behavior
Time Frame: Study days 7, 20, 21, 41, 42, 62, 63
|
Measured by Balloon Analogue Risk Task
|
Study days 7, 20, 21, 41, 42, 62, 63
|
Difference in resting metabolic rate
Time Frame: Study days 7, 21, 42, 63
|
Resting metabolic rate measured by indirect calorimetry
|
Study days 7, 21, 42, 63
|
Difference in physical activity energy expenditure
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Energy expenditure measured by indirect calorimetry during 60-minute steady state exercise
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in gastrointestinal transit time
Time Frame: Study days 20, 41, 62
|
Gastric, small intestine and large intestine transit time measured by SmartPill
|
Study days 20, 41, 62
|
Difference in gastrointestinal pH
Time Frame: Study days 20, 41, 62
|
Gastric, small intestine and large intestine pH measured by SmartPill
|
Study days 20, 41, 62
|
Difference in changes in working memory
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Measured by N-Back task before, during and after exercise
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in changes in spatial working memory
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Measured by emotional Interference task before, during and after exercise
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in changes in spatial memory
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Measured by Matching to Sample test in the morning and afternoon
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in change in reaction time
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Measured by reaction time task before, during and after exercise
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in change in response inhibition
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Measured by Go/No-Go task before, during and after exercise
|
Study days 20, 21, 41, 42, 62, 63
|
Difference in vigilance
Time Frame: Study days 20, 21, 23, 41, 42, 44, 62, 63, 65
|
Measured by scanning visual vigilance task
|
Study days 20, 21, 23, 41, 42, 44, 62, 63, 65
|
Difference in simple visual reaction time
Time Frame: Study days 20, 21, 23, 41, 42, 44, 62, 63, 65
|
Measured by psychomotor vigilance test
|
Study days 20, 21, 23, 41, 42, 44, 62, 63, 65
|
Difference in language-based logical reasoning
Time Frame: Study days 20, 21, 23, 41, 42, 44, 62, 63, 65
|
Measured by grammatical Reasoning task
|
Study days 20, 21, 23, 41, 42, 44, 62, 63, 65
|
Difference in ambulatory vigilance
Time Frame: 48-hours/day during study weeks 0, 2, 3, 5, 6, 8, 9
|
Measured by wrist-worn vigilance monitor
|
48-hours/day during study weeks 0, 2, 3, 5, 6, 8, 9
|
Difference in fecal short chain fatty acids
Time Frame: Study days 6, 18, 21, 23, 27, 39, 42, 44, 48, 60, 63, 65
|
Fecal short chain fatty acid concentrations
|
Study days 6, 18, 21, 23, 27, 39, 42, 44, 48, 60, 63, 65
|
Difference in gut microbiota composition
Time Frame: Study days 6, 18, 21, 23, 27, 39, 42, 44, 48, 60, 63, 65
|
Fecal bacterial community diversity and relative abundance measured by 16S rRNA gene sequencing
|
Study days 6, 18, 21, 23, 27, 39, 42, 44, 48, 60, 63, 65
|
Differences in microRNA concentrations
Time Frame: Study days 20, 21, 41, 42, 62, 63
|
Fasting and post-exercise circulating and exosomal microRNA
|
Study days 20, 21, 41, 42, 62, 63
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: J. Philip Karl, PhD, United States Army Research Institute of Environmental Medicine
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 6, 2019
Primary Completion (Actual)
November 5, 2022
Study Completion (Actual)
November 5, 2022
Study Registration Dates
First Submitted
July 2, 2019
First Submitted That Met QC Criteria
September 30, 2019
First Posted (Actual)
October 1, 2019
Study Record Updates
Last Update Posted (Actual)
December 23, 2022
Last Update Submitted That Met QC Criteria
December 20, 2022
Last Verified
December 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 19-02-HC
- M-10783 (Other Identifier: USMRMC)
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
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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