Effect of Short-chain Fatty Acids on Aerobic Endurance

Metabolism Clinical Trial

Official title:

Effect of Short-chain Fatty Acids on Aerobic Endurance

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06054607
• Other study ID #: 23-13H
• Secondary ID: M-11031
• Status: Recruiting
• Phase: N/A
• Start date: July 21, 2023
• Est. completion date: September 30, 2025

Study information

• Verified date: September 2023
• Source: United States Army Research Institute of Environmental Medicine
• Contact: J. Philip Karl, PhD
• Phone: 508-206-2318
• Email: james.p.karl.civ[@]health.mil
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: September 30, 2025
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 17 Years to 39 Years

Eligibility

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.

Related Conditions & MeSH terms

• Aerobic Endurance
• Metabolism

Intervention

Dietary Supplement:
• High-amylose maize starch+acetate/butyrate
High-amylose maize starch (HAMS), commercially available as Hylon VII (Ingredion, Inc.), to which the SCFA acetate or butyrate has been chemically added. Hylon VII is a HAMS containing ~70% amylose and used in a variety of food products. To produce SCFA-enriched HAMS, Hylon VII is chemically modified through esterification with the SCFA acetate or butyrate.

Other:
• Low-amylose maize starch
Rapidly digestible low-amylose maize starch (0% amylose, 100% amylopectin) sold commercially as AMIOCA (Ingredion, Inc).

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
United States Army Research Institute of Environmental Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Gastrointestinal symptoms	Gastrointestinal symptoms (bloating, pain, nausea, flatulence, discomfort, urge to defecate) measured by 10 cm (0 = low, 10 = high) visual analog scale	Phases 1 and 2, daily on days 1 through 8
Other	Gastrointestinal transit time	Transit time through the stomach, small intestine and large intestine measured using the SmartPill Gastrointestinal monitoring system	Phases 1 and 2, day 8
Other	Circulating biomarkers of substrate utilization	Serum/plasma glucose, insulin, free fatty acids, glycerol, lactate and beta-hydroxybutyrate	Phases 1 and 2, day 8. Measured before (-300minutes, 0minutes) and during (20, 40, 60, 80minutes) steady state endurance exercise.
Other	Total protein content in muscle	Total protein content measured in muscle collected before and after steady state endurance exercise.	Phases 1 and 2, day 8
Other	Total protein expression of molecular markers associated with regulation of muscle metabolism.	Muscle protein signalling measured by Western blotting in muscle collected before and after steady state endurance exercise. Total protein expression of molecular markers associated with regulation of muscle metabolism will be measured to include (but not be limited to): Akt, p-AktSer473, AMPKa, p- AMPKaThr172, PGC-1a , SIRT1, ACC, p-ACCSer79, p53, p-p53Ser15, PDK4, IRS1, p-IRS1Ser302, GSK-3ß, p-GSK-3ßSer9, GSK-3a , p-GSK-3a Ser21, GS, p-GSSer641, and GLUT4.	Phases 1 and 2, day 8
Other	Phosphorylation status of molecular markers associated with regulation of muscle metabolism.	Muscle protein signalling measured by Western blotting in muscle collected before and after steady state endurance exercise. Phosphorylation status of molecular markers associated with regulation of muscle metabolism will be measured to include (but not be limited to): Akt, p-AktSer473, AMPKa, p- AMPKaThr172, PGC-1a , SIRT1, ACC, p-ACCSer79, p53, p-p53Ser15, PDK4, IRS1, p-IRS1Ser302, GSK-3ß, p-GSK-3ßSer9, GSK-3a , p-GSK-3a Ser21, GS, p-GSSer641, and GLUT4 .	Phases 1 and 2, day 8
Other	Pyruvate dehydrogenase activity in muscle	Pyruvate dehydrogenase activity in muscle before and after steady state endurance exercise measured colorimetric assay.	Phases 1 and 2, day 8
Other	Gene expression	Expression of genes regulating carbohydrate and fat oxidation in muscle collected before and after steady state endurance exercise. Individual primers will be used to determine the mRNA expression of known intracellular targets regulating substrate metabolism to include (but not limited to): FAT, PDK4, HADHA, PGC-1a, PPARd, PPAR?, FABP, CPT1a, ACOX1, GS, GSK3a, GLUT4, and HK2.	Phases 1 and 2, day 8
Other	microRNA expression	Expression of genes and microRNA regulating carbohydrate and fat oxidation in muscle collected before and after steady state endurance exercise. microRNA analysis will be conducted using microarray, assessing microRNA that may be associated with substrate metabolism.	Phases 1 and 2, day 8
Other	Gut microbiota composition	Relative abundance of bacterial taxa measured by 16S rRNA amplicon sequencing	Phases 1 and 2, days 1 and 7
Other	Gut microbiome gene content	Relative abundances of microbial genes measured by shotgun metagenomics sequencing	Phases 1 and 2, days 1 and 7
Other	Circulating biomarkers of inflammation	Serum interleukin (IL)-6, IL-10, IL-17, IL-8, IL-1ralpha, IL-1beta, tumor necrosis factor-alpha, interferon gamma	Phases 1 and 2, day 8. Measured before (-300minutes) and at the end (80minutes) of steady state endurance exercise.
Other	Circulating biomarkers of gut barrier function	Serum claudin-3, intestinal fatty acid binding protein and zonulin	Phases 1 and 2, day 8. Measured fasted (-300minutes) and before (0minutes), during (40minutes) and at the end (80minutes) of steady state endurance exercise.
Other	Circulating microRNA	Serum C-microRNA	Phases 1 and 2, day 8. Measured fasted (-15minutes) and at the end (80minutes) of steady state endurance exercise.
Other	Appetite	Appetite (hunger, fullness, desire to eat, prospective consumption) measured by 10 cm (0 = low, 10 = high) visual analog scale	Phases 1 and 2, daily on days 1 through 7
Other	Breath hydrogen and methane	Breath hydrogen and methane concentrations	Phases 1 and 2, day 8. Measured fasting (-300minutes) and before (0minutes) and at the end (80minutes) of steady state endurance exercise
Primary	Run time	Time to complete a 5km treadmill run	Phases 1 and 2, day 8
Secondary	Muscle glycogen content	Muscle glycogen content	Phases 1 and 2, day 8
Secondary	Plasma glucose turnover	Glucose production, utilization and metabolic clearance rate measured during endurance steady state exercise using 6,6-[2H2] glucose tracer	Phases 1 and 2, day 8
Secondary	Whole body substrate oxidation	Carbohydrate and fat oxidation rates measured during endurance steady state exercise using indirect calorimetry	Phase 1 and 2, day 8
Secondary	Serum short-chain fatty acid concentrations	Serum acetate, butyrate and propionate concentrations	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
Secondary	Fecal short-chain fatty acid concentrations	Fecal acetate, butyrate and propionate concentrations	Phases 1 and 2, days 1 and 7
Secondary	Intestinal permeability	Small and large intestine permeability measured by saccharide excretion in urine	Phases 1 and 2, day 8
Secondary	Intestinal pH	pH of the small intestine and large intestine measured using the SmartPill Gastrointestinal monitoring system	Phases 1 and 2, day 8