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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05392556
Other study ID # 21-03-HC
Secondary ID M-10901
Status Recruiting
Phase N/A
First received
Last updated
Start date July 6, 2022
Est. completion date December 2024

Study information

Verified date May 2024
Source United States Army Research Institute of Environmental Medicine
Contact J. Philip Karl, PhD, RD
Phone 508-206-2318
Email james.p.karl.civ@health.mil
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Emerging evidence supports the existence of a microbiota-gut-brain axis through which gut microbes influence cognition, mood and behavior. Targeting this axis with probiotics and/or prebiotics may provide novel strategies for mitigating stress-induced decrements in gastrointestinal and cognitive function. This double-blind, placebo-controlled, randomized, parallel-arm trial will determine the effects of a prebiotic and a probiotic dietary intervention on gastrointestinal, cognitive and physiologic responses to acute military-relevant physical and cognitive stress. Healthy men and women will be recruited and randomized to receive a placebo, probiotic or prebiotic for 4wk. Volunteers will be fed a controlled diet during the 4th week of supplementation. Fecal, blood, urine and saliva samples will be collected. Physical stress will be induced by a weighted walk on a treadmill, and will be followed by a cognitively challenging testing scenario that uses intermittent electric shocks to the abdomen to induce a stress response.


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Study Design


Related Conditions & MeSH terms


Intervention

Dietary Supplement:
Probiotic
Cerebiome (Lallemand Health Solutions): probiotic supplement containing Bifidobacterium longum R0175, Lactobacillus helveticus R0052, and maltodextrin. Dosing: Oral, 3.6 g/d containing 3x10^9 CFU/d (powder form)
Prebiotic
Bimuno-GOS (Clasado Biosciences): Dosing: Oral; 3.6 g/d containing 2.75 g active GOS/d (powder form)
Other:
Placebo
Maltodextrin 3.6 g/d (powder form)

Locations

Country Name City State
United States United States Army Research Institute of Environmental Medicine Natick Massachusetts

Sponsors (3)

Lead Sponsor Collaborator
United States Army Research Institute of Environmental Medicine United States Air Force Research Laboratory, United States Army Combat Capabilities Development Command Soldier Center

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Change from baseline in mean heart rate Heart rate will be measured using a chest-worn heart rate monitor. During stress exposure (up to 4hr) on days 0 and 29
Other Change from baseline in exercise energy expenditure Exercise energy expenditure will be measured by indirect calorimetry During exercise (120min) on days 0 and 29
Other Change from baseline in mean respiratory exchange ratio Respiratory exchange ratio will be measured by indirect calorimetry During exercise (120min) on days 0 and 29
Other Difference from baseline in perceived exertion Perceived exertion will be measured using the validate Borg Ratings of Perceived Exertion scale (range 6 [lightest] to 20 [hardest]) Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29
Other Change from baseline in aggression Measured using the modified Buss-Perry Aggression Questionnaire. The questionnaire is a 29 item questionnaire that assesses aggressive thought patterns ranked on a 5 point continuum. The individual items presents statements like "Once in a while, I can't control the urge to strike another person". The questionnaire instructions will be modified to measure feeling of aggression over the past month, not trait aggression. The results are provided as scores on 4 scales: Physical Aggression [range 9-45], Verbal Aggression [range 5-25], Anger [range 7-35], and Hostility [8-40]; lower is better for all scores. Days 0 and 29
Other Subjective pain ratings The Numeric Pain Rating Scale will be use to quantify subjective pain experienced when receiving electrical shocks during virtual reality cognitive testing (range 0 [none] to 10 [severe]). Day 29
Other Difference from baseline in circulating metabolite levels Serum metabolite levels will be measured via an indwelling venous catheter and untargeted metabolomics analysis (hundreds of metabolites) pending funding availability Before (-20min) exercise and immediately after cognitive stress exposure on days 0 and 29
Other Difference from baseline in fecal metabolite levels Fecal metabolite levels will be measured using untargeted metabolomics (hundreds of metabolites) pending funding availability Pre-intervention, week 3 and week 4
Other Difference from baseline in circulating glucose concentrations Serum glucose concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min) and immediately after (120min) exercise on days 0 and 29
Other Difference from baseline in circulating lactate concentrations Serum lactate concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min) and immediately after (120min) exercise on days 0 and 29
Other Difference from baseline in subjective ratings of fatigue Fatigue will be measured using a numbered visual analog scale ranging from 0 (not tired) to 10 (total exhaustion). Day 0, Week 1, Week 2, Week 3, Day 29
Other Difference from baseline in circulating acetate concentrations Serum acetate concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min) and immediately after (120min) exercise on days 0 and 29
Other Difference from baseline in circulating propionate concentrations Serum propionate concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min) and immediately after (120min) exercise on days 0 and 29
Other Difference from baseline in circulating butyrate concentrations Serum butyrate concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min) and immediately after (120min) exercise on days 0 and 29
Other Difference from baseline in fecal valerate concentrations Valerate concentrations will be measured in fecal samples Pre-intervention, week 3 and week 4
Other Difference from baseline in fecal isobutyrate concentrations Isobutyrate concentrations will be measured in fecal samples Pre-intervention, week 3 and week 4
Other Difference from baseline in fecal isovalerate concentrations Isovalerate concentrations will be measured in fecal samples Pre-intervention, week 3 and week 4
Other Difference from baseline in fecal abundance of probiotic bacteria Abundance of the probiotic bacteria used in the Probiotic intervention arm will be measured using PCR Pre-intervention, week 3 and week 4
Other Difference from baseline in gut microbiota gene content Fecal microbiota gene content will be measured using shotgun metagenomics pending funding availability Pre-intervention, week 3 and week 4
Primary Change from baseline in intestinal permeability A differential sugar absorption test will be used to assess intestinal permeability. Participants will consume 2g sucralose and 4g mannitol dissolved in 180 mL water prior to starting exercise. Participants will then collect all urine produced over the subsequent 4hr. Urine sucralose and mannitol concentrations will be analyzed. Days 0 and 29
Primary Difference from baseline in circulating cortisol concentrations Serum cortisol concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
Secondary Change from baseline in mean heart rate variability Heart rate variability will be measured using a chest-worn heart rate monitor. During stress exposure (up to 4hr) on days 0 and 29.
Secondary Change from baseline in performance on decision making under conditions of ambiguity task Decision making under conditions of ambiguity task will be completed using a virtual reality cognitive testing scenario, which probes shoot/don't-shoot decision-making and the ability to discriminate friend/foe camouflage patterns at varying levels of ambiguity. Days 0 and 29
Secondary Difference from baseline in reaction time. The reaction time task assesses simple and choice response time. In the task participants will be asked to perform a series of simple and choice reaction time trials in response to targets displayed on a computer monitor. Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.
Secondary Difference from baseline in response inhibition The go/no-go task assesses response inhibition. In the task participants will be presented with two, neutral stimuli on a computer screen. Participants will be instructed to press a button on a response device as quickly as possible in response to one visual stimulus, but to withhold from responding to the other visual stimulus. Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.
Secondary Difference from baseline in working memory This N-back task assesses working memory. Participants will be shown a series of letters on a computer screen and will be required to mentally take note of those depicted letters. Participants will then respond either "yes" or "no" if they were the same letters as either 1, 2, and/or 3 letters back. Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.
Secondary Difference from baseline in distractibility to emotional stimuli The Emotional Interference Task task assesses spatial working memory and distractibility to emotional stimuli. Each trial has three phases: stimulus, delay and probe. The stimulus consists of three white dots appearing in pseudo-random locations against a black background. The stimulus phase begins with a "remember this…" instruction, and then the stimulus is presented, followed by a blank screen prior to delay. During the delay, either a neutral or a negative image is presented, selected at random without replacement (both during and across sessions) from an image directory. Finally, the probe is presented, depicting a white ring against a black background to indicate a screen location. The participant is asked to press either YES or NO to indicate whether the indicated location contained or did not contain a dot during the stimulus period. Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.
Secondary Difference from baseline in emotional states measured by the Depression, Anxiety and Stress Scale (DASS) The DASS is a validated 42-item questionnaire designed to measure the three related negative emotional states of depression, anxiety and tension/stress. Score range for all subscales is 0-42; lower is better. Day 0, Week 1, Week 2, Week 3, Day 29
Secondary Difference from baseline in mood state measured by the Profile of Mood States 2-A (POMS2A) The POMS2-A is a validated 65-item inventory of self-reported mood states. Participants rate each of 65 mood-related adjectives on a five-point scale, in response to the question, "How are you feeling right now?" The adjectives factor into six mood sub-scales (tension/anxiety [range 0-40], depression/dejection [range 0-52], anger/hostility [range 0-44], vigor/activity [range 0-36], fatigue/inertia [range 0-24], and confusion/bewilderment [range 0-40], and total mood disturbance [range -36-200]. For all scores except vigor, lower is better. Before (-45min) and immediately after exercise, and after cognitive stress exposure on days 0 and 29
Secondary Difference from baseline in feelings of pleasantness The Feeling Scale is a one-item inventory that measures the extent to which participants feel pleasant or unpleasant. The scale ranges from "very good" (+5) to "very bad" (-5). Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.
Secondary Difference from baseline in feelings of arousal The Felt Arousal Scale is a one-item inventory measures feeling of arousal. The scale ranges from "low arousal" (1) to "high arousal" (6). Before (-45min) exercise, after 40 and 100 min of exercise, and immediately after exercise on days 0 and 29.
Secondary Difference from baseline in gastrointestinal discomfort Subjective ratings of gastrointestinal discomfort will be measured by a modified version of the Irritable Bowel Syndrome-Symptom Severity Score Questionnaire (range 0-470; lower is better). Day 0, Week 1, Week 2, Week 3, Day 29
Secondary Difference from baseline in gastrointestinal symptoms Subjective ratings of gastrointestinal symptoms (e.g., flatulence, constipation, loose stool; range 0-4, higher is better) will be assessed weekly using a modified Gastrointestinal Quality of Life Index. Day 0, Week 1, Week 2, Week 3, Day 29
Secondary Difference from baseline in circulating cytokines concentrations. Serum interleukin (IL)-6, tumor necrosis factor (TNF)a, IL-17, IL-10, IL-8, IL-1ra, IL-1ß, and interferon gamma concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29
Secondary Difference from baseline in circulating dehydroepiandrosterone-sulfate (DHEA-S) concentrations Serum DHEA-S concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29
Secondary Difference from baseline in circulating epinephrine concentrations Plasma epinephrine concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
Secondary Difference from baseline in circulating norepinephrine concentrations Plasma norepinephrine concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
Secondary Difference from baseline in circulating neuropeptide Y concentrations Serum neuropeptide Y concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min) exercise and immediately before cognitive stress exposure on days 0 and 29
Secondary Difference from baseline in circulating brain-derived neurotrophic factor (BDNF) concentrations Plasma BDNF concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min) exercise and immediately before cognitive stress exposure on days 0 and 29
Secondary Difference from baseline in circulating S100 calcium binding protein B (S100B) concentrations Serum S100B concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
Secondary Difference from baseline in circulating lipopolysaccharide concentrations Serum lipopolysaccharide concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
Secondary Difference from baseline in circulating zonulin concentrations Serum zonulin concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
Secondary Difference from baseline in circulating intestinal fatty acid binding protein (I-FABP) concentrations. Serum IFABP concentrations will be measured in serial blood samples collected via an indwelling venous catheter. Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29.
Secondary Difference from baseline in fecal acetate concentrations Acetate concentrations will be measured in fecal samples Pre-intervention, week 3 and week 4
Secondary Difference from baseline in fecal propionate concentrations Propionate concentrations will be measured in fecal samples Pre-intervention, week 3 and week 4
Secondary Difference from baseline in fecal butyrate concentrations Butyrate concentrations will be measured in fecal samples Pre-intervention, week 3 and week 4
Secondary Difference from baseline in gut microbiota composition Fecal microbiota composition will be measured using 16S rRNA gene amplicon sequencing Pre-intervention, week 3 and week 4
Secondary Change from baseline in salivary secretory immunoglobulin A Secretory immunoglobulin A concentrations will be measured in saliva Day 0 and Day 29
Secondary Difference from baseline in salivary cortisol concentrations Cortisol concentrations will be serially measured in saliva Before (-20min), during (60min) and immediately after (120min) exercise and immediately before and after cognitive stress exposure on days 0 and 29
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