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| ID | Type | Description | Link |
|---|---|---|---|
| M-11031 | Other Identifier | HQ US Army Medical Research and Development Command IRBO |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low-amylose maize starch | Placebo Comparator | Low-amylose maize starch (AMIOCA; Ingredion, Inc). |
|
| High-amylose maize starch+acetate/butyrate | Active Comparator | High-amylose maize starch, (Hylon VII; Ingredion, Inc.) to which the SCFA acetate or butyrate has been chemically added. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High-amylose maize starch+acetate/butyrate | Dietary Supplement | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Run time | Time to complete a 5km treadmill run | Phases 1 and 2, day 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Muscle glycogen content | Muscle glycogen content | Phases 1 and 2, day 8 |
| Plasma glucose turnover | Glucose production, utilization and metabolic clearance rate measured during endurance steady state exercise using 6,6-[2H2] glucose tracer |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Circulating biomarkers of substrate utilization |
Inclusion Criteria:
Exclusion Criteria:
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)
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| Name | Affiliation | Role |
|---|---|---|
| J. Philip Karl, PhD | United States Army Research Institute of Environmental Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| United States Army Research Institute of Environmental Medicine | Natick | Massachusetts | 01760 | United States |
De-identified data and samples will remain under the control of the Principal Investigator and may be shared with outside collaborators for future research with appropriate data sharing agreements and legal/ethical approvals. De-identified microbiome sequencing data may be posted in a publicly available data repository.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Sep 21, 2023 | Dec 18, 2025 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D002087 | Butyrates |
| ID | Term |
|---|---|
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005232 | Fatty Acids, Volatile |
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| Low-amylose maize starch | Other | Rapidly digestible low-amylose maize starch (0% amylose, 100% amylopectin) sold commercially as AMIOCA (Ingredion, Inc). |
|
| Phases 1 and 2, day 8 |
| Whole body substrate oxidation | Carbohydrate and fat oxidation rates measured during endurance steady state exercise using indirect calorimetry | Phase 1 and 2, day 8 |
| 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 |
| Fecal short-chain fatty acid concentrations | Fecal acetate, butyrate and propionate concentrations | Phases 1 and 2, days 1 and 7 |
| Intestinal permeability | Small and large intestine permeability measured by saccharide excretion in urine | Phases 1 and 2, day 8 |
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. |
| 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 |
| 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, AMPKα, p- AMPKαThr172, PGC-1α , SIRT1, ACC, p-ACCSer79, p53, p-p53Ser15, PDK4, IRS1, p-IRS1Ser302, GSK-3β, p-GSK-3βSer9, GSK-3α , p-GSK-3α Ser21, GS, p-GSSer641, and GLUT4. | Phases 1 and 2, day 8 |
| 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, AMPKα, p- AMPKαThr172, PGC-1α , SIRT1, ACC, p-ACCSer79, p53, p-p53Ser15, PDK4, IRS1, p-IRS1Ser302, GSK-3β, p-GSK-3βSer9, GSK-3α , p-GSK-3α Ser21, GS, p-GSSer641, and GLUT4 . | Phases 1 and 2, day 8 |
| 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 |
| 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-1α, PPARδ, PPARγ, FABP, CPT1a, ACOX1, GS, GSK3α, GLUT4, and HK2. | Phases 1 and 2, day 8 |
| 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 |
| Gut microbiota composition | Relative abundance of bacterial taxa measured by 16S rRNA amplicon sequencing | Phases 1 and 2, days 1 and 7 |
| Gut microbiome gene content | Relative abundances of microbial genes measured by shotgun metagenomics sequencing | Phases 1 and 2, days 1 and 7 |
| 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. |
| 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. |
| Circulating microRNA | Serum C-microRNA | Phases 1 and 2, day 8. Measured fasted (-15minutes) and at the end (80minutes) of steady state endurance exercise. |
| 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 |
| 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 |
| D005227 |
| Fatty Acids |
| D008055 | Lipids |