Antibiotic Resistance and Microbiome in Children Aged 6-59 Months in Nouna, Burkina Faso

NCT03187834 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 17-22036
• Study Type: interventional
• Target: 252
• Locations: 2 countries
• Sites: 2

Brief Summary

The use of antibiotics has saved millions of human lives, however consumption of antibiotics can select for antibiotic resistant organisms and may lead to changes in commensal microbiome. This study is designed to estimate the effect of antibiotic consumption on microbiome in a rural region of rural Burkina Faso. Changes in the intestinal and nasopharyngeal microbiome and resistome following a short course of antibiotics will be measured.

Conditions

Child Development

Keywords

infection; azithromycin; amoxicillin; co-trimoxazole; trachoma; mass treatment

Outcome Measures

Primary Outcomes (1)

• Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome

  The primary outcome of the study was pre-specified as α-diversity (inverse Simpson's) at the genus level, expressed in effective number. Simpson's Alpha Diversity were obtained at Baseline and Post-treatment in this study. The minimum of Simpson's index of diversity is 0, there is no maximum. Higher Simpson's index of diversity means more diverse. There are no subscales.

  Baseline and Day 9

Secondary Outcomes (13)

• Simpson's Index of Diversity (Alpha Diversity) in Microbiome

  Day 9

• Weight-for-height Z-score

  Day 35

• Height-for-age Z-score

  Day 35

• Weight-for-age Z-score

  Day 35

• Mid-upper Arm Circumference

  Day 35

Study Arms (4)

Azithromycin

ACTIVE COMPARATOR

Comparison of nasopharyngeal and rectal microbiome in children receiving Azithromycin versus children receiving placebo Children aged 6 months to 59 months will be measured and weighed then, they will be randomized to one of the study arm and treated for 5 days. Children will receive treatment everyday, once a day as is: Azithromycin: 10 mg/kg once daily on Day 1, then 5 mg/kg once daily Days 2-5

Drug: Azithromycin

Amoxicillin

ACTIVE COMPARATOR

Comparison of nasopharyngeal and rectal microbiome in children receiving Amoxicillin versus children receiving placebo Children aged 6 months to 59 months will be measured and weighed then, they will be randomized to one of the study arm. Children will receive treatment everyday, twice a day as is: Amoxicillin: 25 mg/kg/day, divided into twice daily doses for Days 1-5

Drug: Amoxicillin

Cotrimoxazole

ACTIVE COMPARATOR

Comparison of nasopharyngeal and rectal microbiome in children receiving Cotri-moxazole versus children receiving placebo Children aged 6 months to 59 months will be measured and weighed then, they will be randomized to one of the study arm. Children will receive treatment everyday, once a day as is: Co-trimoxazole: 240 mg daily for Days 1-5

Drug: Cotrimoxazole

Placebo

PLACEBO COMPARATOR

Comparison of nasopharyngeal and rectal microbiome in children receiving placebo versus children receiving antibiotics Children aged 6 months to 59 months will be measured and weighed then, they will be randomized to one of the study arm. Children will receive Placebo everyday, once a day.

Drug: Placebo

Interventions

Azithromycin DRUG

Children in this arm will receive Azithromycin once a day.

Also known as: Zithromax

Azithromycin

Amoxicillin DRUG

Children in this arm will receive Amoxicillin twice a day.

Amoxicillin

Cotrimoxazole DRUG

Children in this arm will receive co-trimoxazole once a day.

Cotrimoxazole

Placebo DRUG

Children in this arm will receive Placebo once a day.

Placebo

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may not qualify if:

• Children who are allergic to any of the study antibiotics will be excluded. Individuals aged under 6 months and 5 years or older will be excluded. Children already receiving antibiotics for an ongoing disease will be excluded.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Centre de Recherche en Sante de Nouna, Burkina Faso: collaborator
• Heidelberg University: collaborator

Study Sites (2)

UCSF Proctor Foundation

San Francisco, California, 94143, United States

Location

Centre de Recherche en Santé de Nouna

Nouna, Burkina Faso

Location

Related Publications (5)

• Oldenburg CE, Hinterwirth A, Worden L, Sie A, Dah C, Ouermi L, Coulibaly B, Zhong L, Chen C, Ruder K, Lietman TM, Keenan JD, Doan T. Indirect effect of oral azithromycin on the gut resistome of untreated children: a randomized controlled trial. Int Health. 2021 Feb 24;13(2):130-134. doi: 10.1093/inthealth/ihaa029.

  PMID: 32556194 DERIVED

• Dennis EG, Sie A, Ouermi L, Dah C, Tapsoba C, Zabre P, Barnighausen T, O'Brien KS, Lebas E, Keenan JD, Oldenburg CE. Short-term weight gain among preschool children in rural Burkina Faso: a secondary analysis of a randomised controlled trial. BMJ Open. 2019 Jul 29;9(7):e029634. doi: 10.1136/bmjopen-2019-029634.

  PMID: 31362969 DERIVED

• Oldenburg CE, Sie A, Coulibaly B, Ouermi L, Dah C, Tapsoba C, Barnighausen T, Lebas E, Arzika AM, Cummings S, Zhong L, Lietman TM, Keenan JD, Doan T. Indirect Effect of Azithromycin Use on the Intestinal Microbiome Diversity of Untreated Children: A Randomized Trial. Open Forum Infect Dis. 2019 Feb 6;6(3):ofz061. doi: 10.1093/ofid/ofz061. eCollection 2019 Mar.

  PMID: 30895203 DERIVED

• Oldenburg CE, Sie A, Coulibaly B, Ouermi L, Dah C, Tapsoba C, Barnighausen T, Ray KJ, Zhong L, Cummings S, Lebas E, Lietman TM, Keenan JD, Doan T. Effect of Commonly Used Pediatric Antibiotics on Gut Microbial Diversity in Preschool Children in Burkina Faso: A Randomized Clinical Trial. Open Forum Infect Dis. 2018 Nov 2;5(11):ofy289. doi: 10.1093/ofid/ofy289. eCollection 2018 Nov.

  PMID: 30515431 DERIVED

• Sie A, Dah C, Ouermi L, Tapsoba C, Zabre P, Barnighausen T, Lebas E, Arzika AM, Snyder BM, Porco TC, Lietman TM, Keenan JD, Oldenburg CE. Effect of Antibiotics on Short-Term Growth among Children in Burkina Faso: A Randomized Trial. Am J Trop Med Hyg. 2018 Sep;99(3):789-796. doi: 10.4269/ajtmh.18-0342. Epub 2018 Jul 12.

  PMID: 30014828 DERIVED

MeSH Terms

Conditions

Infections; Trachoma

Interventions

Azithromycin; Amoxicillin; Trimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Conjunctivitis, Bacterial; Eye Infections, Bacterial; Bacterial Infections; Bacterial Infections and Mycoses; Chlamydia Infections; Chlamydiaceae Infections; Gram-Negative Bacterial Infections; Eye Infections; Conjunctivitis; Conjunctival Diseases; Eye Diseases; Corneal Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Thomas Lietman
• Organization: F.I. Proctor Foundation, University of Califonia, San Francisco

tom.lietman@ucsf.edu

415-502-2662

Study Officials

• Thomas M Lietman, MD

  UCSF F.I. Proctor Foundation

  PRINCIPAL INVESTIGATOR

• Catherine E Oldenburg, ScD

  UCSF F.I. Proctor Foundation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Households will be randomized to one of four treatment arms (azithromycin, cotrimoxazole, amoxicillin, or placebo), and each child age 6-59 months in the household will receive 5 days of treatment. One child within each of the antibiotic households will be randomly selected to receive placebo instead of the antibiotc, to allow for study of indirect effects of antibiotic use

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: June 15, 2017
• Study Start: July 4, 2017
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2019
• Last Updated: March 2, 2023
• Results First Posted: March 2, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); BU (1)