Clinical trial NCT06054607: Effect of Short-chain Fatty Acids on Aerobic Endurance
Official title: Effect of Short-chain Fatty Acids on Aerobic Endurance
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aerobic Endurance
Metabolism
Keywords: short-chain fatty acid
microbiome
endurance
fiber
resistant starch
gastrointestinal
Lead sponsor: United States Army Research Institute of Environmental Medicine
Sponsor class: FED
First posted: 2023-09-26
Enrollment: 12
Sex: ALL
Minimum age (years): 17
Maximum age (years): 39
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: Randomized, double-blind, placebo-controlled crossover study designed to determine the effects of increasing colonic short-chain fatty acid (SCFA) content on aerobic endurance in healthy adults, and to identify underpinning mechanisms. In random order, healthy physically active adults will consume provided diets low in fiber and supplemented with SCFA-enriched high amylose maize starch (a poorly digested resistant starch considered a fermentable fiber) or low amylose maize starch (a rapidly digestible starch) for 1-week separated by a ≥2-week washout. At the end of each intervention period, participants will complete an endurance exercise bout followed by a time trial. Biological samples will be collected to assess muscle and whole body metabolism, gut microbiota, inflammation, and gastrointestinal function.


Eligibility criteria: 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.
* Routinely participate in moderate or higher intensity aerobic and/or resistance exercise at least 4 days per week for ≥20 min/d.
* Meet Army weight for height and body composition standards as defined in Army Regulation 600-9.
* Self-reports a usual bowel movement frequency of every other day or more often.
* Willing to refrain from the use of caffeine, alcohol, and nicotine while consuming study diets.
* Willing to refrain from all dietary supplements beginning 2 weeks prior to study start and throughout study participation.
* Willing to refrain from consumption of any foods containing live microorganisms (e.g., yogurt, kefir, kombucha) or added prebiotics (e.g. Fiber One products) beginning 2 weeks prior to study start and throughout study participation.
* Willing to participate in all study procedures.
* Females must have normal menstrual cycles between 26-32 days in duration; 5 menstrual cycles within the past 6 months; or be using an oral/hormonal contraceptive which contains low-dose estrogen/progesterone to maintain continuous levels throughout the 28-day cycle (i.e., no placebos).

Exclusion Criteria:

* Females who are pregnant, expecting to become pregnant during the study, or breastfeeding.
* Any of the following medical conditions:

Cardiac disease (including arrhythmia or fast or skipped heart beats) Hypertension Musculoskeletal injuries that compromise exercise capability Metabolic or cardiovascular abnormalities (e.g., kidney disease, diabetes, etc.) Disease of the GI tract including, but not limited to diverticulitis, inflammatory bowel disease, irritable bowel syndrome, peptic ulcer disease, Crohn's disease, and ulcerative colitis Allergy to skin adhesive or Lidocaine (or other local anesthetic being used in place of Lidocaine) Suspected or known strictures, fistulas, or physiological/mechanical GI obstruction History of gastric bezoar Swallowing disorders; severe dysphagia to food or pills Implanted or portable electro-mechanical medical devices (e.g., pacemaker)

* Colonoscopy within 3 months of study participation.
* Any use of antibiotics or antimycotics, except topical antibiotics/antimycotics, within 3 months of study participation.
* Regular (i.e., weekly or more frequent) use of over-the-counter medications (including antacids, laxatives, stool softeners, and anti-diarrheals) unless approved by study PI.
* Use of medication (i.e., diabetes medications, statins, corticosteroids, etc.) that affects macronutrient utilization and/or the ability to participate in strenuous exercise.
* Anemia (HCT \<38 for men and \<34 for women) or Sickle Cell Anemia/Trait.
* Not willing or able to follow all study procedures and diet/exercise restrictions.
* Allergies, intolerances, unwillingness or inability to eat provided foods and beverages.
* Following vegetarian/vegan diet or other highly restrictive diet (e.g., ketogenic diet, very high protein diet, Paleo diet, etc.).
* Any previous blood donation within the previous 8 weeks that when combined with the volume of blood collected for the study within any 8-week period would exceed 550mL.

Primary outcomes:
measure: Run time
timeFrame: Phases 1 and 2, day 8
Secondary outcomes:
measure: Muscle glycogen content
timeFrame: Phases 1 and 2, day 8
measure: Plasma glucose turnover
timeFrame: Phases 1 and 2, day 8
measure: Whole body substrate oxidation
timeFrame: Phase 1 and 2, day 8
measure: Serum short-chain fatty acid concentrations
timeFrame: Phases 1 and 2, day 8. Measured fasted (-300 minutes) and before (0 minutes) and at the end (80 minutes) of steady state endurance exercise
measure: Fecal short-chain fatty acid concentrations
timeFrame: Phases 1 and 2, days 1 and 7
measure: Intestinal permeability
timeFrame: Phases 1 and 2, day 8
measure: Intestinal pH
timeFrame: Phases 1 and 2, day 8
Other outcomes:
measure: Gastrointestinal symptoms
timeFrame: Phases 1 and 2, daily on days 1 through 8
measure: Gastrointestinal transit time
timeFrame: Phases 1 and 2, day 8
measure: Circulating biomarkers of substrate utilization
timeFrame: Phases 1 and 2, day 8. Measured before (-300minutes, 0minutes) and during (20, 40, 60, 80minutes) steady state endurance exercise.
measure: Total protein content in muscle
timeFrame: Phases 1 and 2, day 8
measure: Total protein expression of molecular markers associated with regulation of muscle metabolism.
timeFrame: Phases 1 and 2, day 8
measure: Phosphorylation status of molecular markers associated with regulation of muscle metabolism.
timeFrame: Phases 1 and 2, day 8
measure: Pyruvate dehydrogenase activity in muscle
timeFrame: Phases 1 and 2, day 8
measure: Gene expression
timeFrame: Phases 1 and 2, day 8
measure: microRNA expression
timeFrame: Phases 1 and 2, day 8
measure: Gut microbiota composition
timeFrame: Phases 1 and 2, days 1 and 7
measure: Gut microbiome gene content
timeFrame: Phases 1 and 2, days 1 and 7
measure: Circulating biomarkers of inflammation
timeFrame: Phases 1 and 2, day 8. Measured before (-300minutes) and at the end (80minutes) of steady state endurance exercise.
measure: Circulating biomarkers of gut barrier function
timeFrame: Phases 1 and 2, day 8. Measured fasted (-300minutes) and before (0minutes), during (40minutes) and at the end (80minutes) of steady state endurance exercise.
measure: Circulating microRNA
timeFrame: Phases 1 and 2, day 8. Measured fasted (-15minutes) and at the end (80minutes) of steady state endurance exercise.
measure: Appetite
timeFrame: Phases 1 and 2, daily on days 1 through 7
measure: Breath hydrogen and methane
timeFrame: Phases 1 and 2, day 8. Measured fasting (-300minutes) and before (0minutes) and at the end (80minutes) of steady state endurance exercise
Locations:
city: Natick
country: United States
facility: United States Army Research Institute of Environmental Medicine
state: Massachusetts
Study officials:
affiliation: United States Army Research Institute of Environmental Medicine
name: J. Philip Karl, PhD
role: PRINCIPAL_INVESTIGATOR
References: