Comparative Efficacy of Antibiotics for Small Intestine Bacterial Overgrowth in Bangladeshi Children

NCT07451171 | Recruiting Phase 2 DMC

• 2 other identifiers: 3025801R01HD113733-01A1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this Phase IIa study is to identify the most effective antibiotic regimen to treat small intestine bacterial overgrowth (SIBO) in impoverished Bangladeshi children.

Conditions

Small Intestine Bacterial Overgrowth

Keywords

environmental enteric dysfunction

Outcome Measures

Primary Outcomes (1)

• Conversion to Glucose Hydrogen Breath Test (GHBT) Negativity at Day 15

  GHBT negativity will be defined as no breath hydrogen value ≥20 ppm over the patient's baseline during the course of the test. If any breath hydrogen value during the GHBT is \>20 ppm over the patient's baseline, the test will be deemed positive.

  Day 15

Secondary Outcomes (5)

• Conversion to GHBT Negativity at Day 45

  Day 45

• Average Glucose Hydrogen Breath Test Area Under the Curve

  Baseline, day 15, day 45

• Fecal Myeloperoxidase

  Baseline, day 15, day 45

• Fecal Neopterin

  Baseline, day 15, day 45

• Fecal Calprotectin

  Baseline, day 15, day 45

Study Arms (3)

Metronidazole

EXPERIMENTAL

14-day oral course

Drug: Metronidazole

Trimethoprim-sulfamethoxazole and Metronidazole

EXPERIMENTAL

14-day oral course

Drug: Trimethoprim-sulfamethoxazole (TMP/SMX); Drug: Metronidazole

Amoxicillin-Clavulanate

EXPERIMENTAL

14-day oral course

Drug: Amoxicillin-Clavulanate (4:1 formulation)

Interventions

Trimethoprim-sulfamethoxazole (TMP/SMX) DRUG

8-10 mg/kg/day divided every 12 hours, with a maximum 160 mg/dose; dosing based on Trimethoprim

Trimethoprim-sulfamethoxazole and Metronidazole

Metronidazole DRUG

Administered alone: 20-30 mg/kg/day divided every 8 hours, with a maximum 750 mg/dose Co-administered with Trimethoprim-sulfamethoxazole: 35-50 mg/kg/day divided every 8 hours, with a maximum 750 mg/dose

Metronidazole; Trimethoprim-sulfamethoxazole and Metronidazole

Amoxicillin-Clavulanate (4:1 formulation) DRUG

20-40 mg amoxicillin/kg/day divided every 8 hours, with maximum daily dose of 1,500 mg

Amoxicillin-Clavulanate

Eligibility Criteria

• Age: 1 Year - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Positive glucose hydrogen breath test (GHBT)
• Weight-for-age Z score \> -1
• Length-for-age Z score \> -1

You may not qualify if:

• Presence of known chronic or congenital illness, including developmental delay
• Presence of acute gastrointestinal illness in the preceding 14 days
• Antibiotic use in the preceding 14 days
• Previous adverse reaction to any of the three study medications or other drugs in the same antibiotic classes
• Sibling previously enrolled in this study

Sponsors & Collaborators

• National Institutes of Health (NIH): collaborator
• University of Virginia: lead
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator
• Virginia Commonwealth University: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)

Dhaka, Bangladesh

RECRUITING

Related Publications (11)

• Tahan S, Melli LC, Mello CS, Rodrigues MS, Bezerra Filho H, de Morais MB. Effectiveness of trimethoprim-sulfamethoxazole and metronidazole in the treatment of small intestinal bacterial overgrowth in children living in a slum. J Pediatr Gastroenterol Nutr. 2013 Sep;57(3):316-8. doi: 10.1097/MPG.0b013e3182952e93.

  PMID: 23974062 BACKGROUND

• Mello CS, Rodrigues MSDC, Filho HBA, Melli LCFL, Tahan S, Pignatari ACC, de Morais MB. Fecal microbiota analysis of children with small intestinal bacterial overgrowth among residents of an urban slum in Brazil. J Pediatr (Rio J). 2018 Sep-Oct;94(5):483-490. doi: 10.1016/j.jped.2017.09.003. Epub 2017 Oct 16.

  PMID: 29049893 BACKGROUND

• Donowitz JR, Haque R, Kirkpatrick BD, Alam M, Lu M, Kabir M, Kakon SH, Islam BZ, Afreen S, Musa A, Khan SS, Colgate ER, Carmolli MP, Ma JZ, Petri WA Jr. Small Intestine Bacterial Overgrowth and Environmental Enteropathy in Bangladeshi Children. mBio. 2016 Jan 12;7(1):e02102-15. doi: 10.1128/mBio.02102-15.

  PMID: 26758185 BACKGROUND

• Vonaesch P, Morien E, Andrianonimiadana L, Sanke H, Mbecko JR, Huus KE, Naharimanananirina T, Gondje BP, Nigatoloum SN, Vondo SS, Kaleb Kandou JE, Randremanana R, Rakotondrainipiana M, Mazel F, Djorie SG, Gody JC, Finlay BB, Rubbo PA, Wegener Parfrey L, Collard JM, Sansonetti PJ; Afribiota Investigators. Stunted childhood growth is associated with decompartmentalization of the gastrointestinal tract and overgrowth of oropharyngeal taxa. Proc Natl Acad Sci U S A. 2018 Sep 4;115(36):E8489-E8498. doi: 10.1073/pnas.1806573115. Epub 2018 Aug 20.

  PMID: 30126990 BACKGROUND

• Pereira SP, Khin-Maung-U, Bolin TD, Duncombe VM, Nyunt-Nyunt-Wai, Myo-Khin, Linklater JM. A pattern of breath hydrogen excretion suggesting small bowel bacterial overgrowth in Burmese village children. J Pediatr Gastroenterol Nutr. 1991 Jul;13(1):32-8. doi: 10.1097/00005176-199107000-00006.

  PMID: 1833523 BACKGROUND

• Mello CS, Tahan S, Melli LC, Rodrigues MS, de Mello RM, Scaletsky IC, de Morais MB. Methane production and small intestinal bacterial overgrowth in children living in a slum. World J Gastroenterol. 2012 Nov 7;18(41):5932-9. doi: 10.3748/wjg.v18.i41.5932.

  PMID: 23139610 BACKGROUND

• dos Reis JC, de Morais MB, Oliva CA, Fagundes-Neto U. Breath hydrogen test in the diagnosis of environmental enteropathy in children living in an urban slum. Dig Dis Sci. 2007 May;52(5):1253-8. doi: 10.1007/s10620-006-9288-9. Epub 2007 Mar 20.

  PMID: 17372830 BACKGROUND

• Gasbarrini A, Corazza GR, Gasbarrini G, Montalto M, Di Stefano M, Basilisco G, Parodi A, Usai-Satta P, Vernia P, Anania C, Astegiano M, Barbara G, Benini L, Bonazzi P, Capurso G, Certo M, Colecchia A, Cuoco L, Di Sario A, Festi D, Lauritano C, Miceli E, Nardone G, Perri F, Portincasa P, Risicato R, Sorge M, Tursi A; 1st Rome H2-Breath Testing Consensus Conference Working Group. Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference. Aliment Pharmacol Ther. 2009 Mar 30;29 Suppl 1:1-49. doi: 10.1111/j.1365-2036.2009.03951.x.

  PMID: 19344474 BACKGROUND

• Donowitz JR, Parikh HI, Taniuchi M, Gilchrist CA, Haque R, Kirkpatrick BD, Alam M, Kakon SH, Islam BZ, Afreen S, Kabir M, Nayak U, Colgate ER, Carmolli MP, Petri WA Jr. Increased Fecal Lactobacillus Is Associated With a Positive Glucose Hydrogen Breath Test in Bangladeshi Children. Open Forum Infect Dis. 2019 Jun 1;6(7):ofz266. doi: 10.1093/ofid/ofz266. eCollection 2019 Jul.

  PMID: 31281862 BACKGROUND

• Pimentel M, Saad RJ, Long MD, Rao SSC. ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth. Am J Gastroenterol. 2020 Feb;115(2):165-178. doi: 10.14309/ajg.0000000000000501.

  PMID: 32023228 BACKGROUND

• Donowitz JR, Pu Z, Lin Y, Alam M, Ferdous T, Shama T, Taniuchi M, Islam MO, Kabir M, Nayak U, Faruque ASG, Haque R, Ma JZ, Petri WA Jr. Small Intestine Bacterial Overgrowth in Bangladeshi Infants Is Associated With Growth Stunting in a Longitudinal Cohort. Am J Gastroenterol. 2022 Jan 1;117(1):167-175. doi: 10.14309/ajg.0000000000001535.

  PMID: 34693912 BACKGROUND

MeSH Terms

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination; Metronidazole; Amoxicillin-Potassium Clavulanate Combination; Dosage Forms

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Technology, Pharmaceutical; Investigative Techniques

Study Officials

• Jeffrey R Donowitz, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

• Rashidul Haque, MBBS, PhD

  International Centre for Diarrhoeal Disease Research, Bangladesh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeffrey R Donowitz, MD

CONTACT

434-243-8824; jrd9d@virginia.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: March 5, 2026
• Study Start: April 18, 2026
• Primary Completion (Estimated): August 2, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)