Investigation of the Gut Microbiota in Regulating Nutrient Absorption in Humans

NCT02037295 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 99991404514-DK-N045
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

We propose to study both stool and urine energy loss in 24 individuals on two experimental diets (50% increased and 50% reduced nutrient load relative to body size) in a random cross-over design. Following this over/underfeeding, volunteers will also be randomly assigned to a placebo versus oral antibiotic medication arm. This study will extend our previous findings by investigating whether 1) nutrient absorption changes upon similar increases/decreases in relative nutrient load and 2) whether manipulation of gut microbial communities with antibiotics alters nutrient absorption and 3) how these changes may affect glucose tolerance and fat storage.

Conditions

Obesity

Keywords

Gut Microbiota; Obesity; Absorption; Overfeeding

Outcome Measures

Primary Outcomes (2)

• Stool Calories During OF and UF

  Calculated as stool calories (kcal/day) x 100/ingested calories (kcal/day)

  Days 5-7 and 11-13

• Stool Calories During Vancomycin and Placebo

  Calculated as stool calories (kcal/day) x 100/ingested calories (kcal/day), vancomycin compared to placebo

  Days 23-25

Secondary Outcomes (5)

• Urine Calories During OF and UF

  Days 5-7 and 11-13

• Urine Calories During Vancomycin and Placebo

  Days 23-25

• Change in 2 Hour Glucose Tolerance From Day 16 to Day 28 During Vancomycin and Placebo

  Day 16 and day 28

• Overall Gut Microbial Colonization During OF and UF

  Days 5-7 and 11-13

• Overall Gut Microbial Colonization During Vancomycin and Placebo

  Days 23-25

Study Arms (4)

OF_UF Vancomycin

EXPERIMENTAL

Healthy volunteers assigned overfeeding diet, underfeeding diet, and then vancomycin

Drug: Vancomycin; Other: Overfeeding diet (OF); Other: Underfeeding diet (UF)

OF_UF Placebo

PLACEBO COMPARATOR

Healthy volunteers assigned overfeeding diet, underfeeding diet, and then placebo

Drug: Placebo oral tablet; Other: Overfeeding diet (OF); Other: Underfeeding diet (UF)

UF_OF Vancomycin

EXPERIMENTAL

Healthy volunteers assigned underfeeding diet, overfeeding diet, and then vancomycin

Drug: Vancomycin; Other: Overfeeding diet (OF); Other: Underfeeding diet (UF)

UF_OF Placebo

PLACEBO COMPARATOR

Healthy volunteers assigned underfeeding diet, overfeeding diet, and then placebo

Drug: Placebo oral tablet; Other: Overfeeding diet (OF); Other: Underfeeding diet (UF)

Interventions

Vancomycin DRUG

Vancomycin 125mg orally four times per day for 12 days

OF_UF Vancomycin; UF_OF Vancomycin

Placebo oral tablet DRUG

Placebo pills orally four times per day for 12 days

OF_UF Placebo; UF_OF Placebo

Overfeeding diet (OF) OTHER

Diet in which the calories are 150% of their weight maintaining energy requirements

OF_UF Placebo; OF_UF Vancomycin; UF_OF Placebo; UF_OF Vancomycin

Underfeeding diet (UF) OTHER

Diet in which the calories are 50% of their weight maintaining energy requirements

OF_UF Placebo; OF_UF Vancomycin; UF_OF Placebo; UF_OF Vancomycin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Free of acute and chronic diseases (especially GI disorders) as determined by medical history, physical examination and laboratory tests.
• Individuals may be taking laxative drugs but they must be discontinued 3 or more weeks before admission.
• Age 18-45 y (in order to minimize the affect of aging on nutrient absorption).

You may not qualify if:

• Because it is unclear how chronic illnesses or substance abuse could affect nutrient absorption we will exclude volunteers with chronic diseases or current substance abuse. This is especially important because the limited number of study subjects in this study will make it hard to control for these confounders. We will therefore exclude subjects with a history or clinical manifestation of:
• Current smoking
• Type 2 diabetes (according to the World Health Organization diagnostic criteria)
• Endocrine disorders, such as Cushing s disease, pituitary disorders, and hypo- and hyperthyroidism
• HIV infection (self-report), due to effects on weight and body composition of HIV and medications used to treat HIV
• Active tuberculosis (self-report)
• Asthma on active daily treatment with medications
• Pulmonary disorders including physician diagnosed chronic obstructive pulmonary diseases and obstructive sleep apnea syndrome
• Cardiovascular diseases, including coronary heart disease, heart failure, arrhythmias, and peripheral artery disease
• Hypertension (according to the World Health Organization diagnostic criteria), treated or uncontrolled
• Gastrointestinal disease, including inflammatory bowel diseases (e.g. Crohn s disease and ulcerative colitis), malabsorption syndromes (e.g. celiac disease), gastric ulcer (active) and irritable bowel syndrome.
• Lactose intolerance
• Anemia (defined as hemoglobin \< 11 mg/dl), leucopenia (defined as white blood cell count \< 4,000/microL) or thrombocytopenia (defined as platelet count \< 150,000/microL)
• Liver disease, including non-alcoholic fatty liver disease or current elevated liver enzymes over 1.5 times the normal range for AST, ALT or GGT or a history and physical exam that indicates a potential liver disease as describe by Giannini et al
• Evidence of chronic renal disease as defined by estimated glomerular filtration rate of \< 60 ml/min or evidence of overt proteinuria on urine dipstick.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

NIDDK, Phoenix

Phoenix, Arizona, 85014, United States

Location

Related Publications (5)

• Yanovski SZ, Yanovski JA. Obesity. N Engl J Med. 2002 Feb 21;346(8):591-602. doi: 10.1056/NEJMra012586. No abstract available.

  PMID: 11856799 BACKGROUND

• Weststrate JA, Dekker J, Stoel M, Begheijn L, Deurenberg P, Hautvast JG. Resting energy expenditure in women: impact of obesity and body-fat distribution. Metabolism. 1990 Jan;39(1):11-7. doi: 10.1016/0026-0495(90)90141-x.

  PMID: 2294371 BACKGROUND

• Segal KR, Dunaif A. Resting metabolic rate and postprandial thermogenesis in polycystic ovarian syndrome. Int J Obes. 1990 Jul;14(7):559-67.

  PMID: 2228390 BACKGROUND

• Basolo A, Hohenadel M, Ang QY, Piaggi P, Heinitz S, Walter M, Walter P, Parrington S, Trinidad DD, von Schwartzenberg RJ, Turnbaugh PJ, Krakoff J. Effects of underfeeding and oral vancomycin on gut microbiome and nutrient absorption in humans. Nat Med. 2020 Apr;26(4):589-598. doi: 10.1038/s41591-020-0801-z. Epub 2020 Mar 23.

  PMID: 32235930 RESULT

• Basolo A, Parrington S, Ando T, Hollstein T, Piaggi P, Krakoff J. Procedures for Measuring Excreted and Ingested Calories to Assess Nutrient Absorption Using Bomb Calorimetry. Obesity (Silver Spring). 2020 Dec;28(12):2315-2322. doi: 10.1002/oby.22965. Epub 2020 Oct 7.

  PMID: 33029899 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Jonathan Krakoff, M.D.
• Organization: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

jkrakoff@mail.nih.gov

(602) 200-5217

Study Officials

• Jonathan Krakoff, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2014
• First Posted: January 15, 2014
• Study Start: January 14, 2014
• Primary Completion: March 29, 2019
• Study Completion: March 29, 2019
• Last Updated: July 31, 2020
• Results First Posted: July 31, 2020

Record last verified: 2019-03-29

Locations

US (1)