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

Child Development Clinical Trial

— ARMCA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03187834
• Other study ID #: 17-22036
• Status: Completed
• Phase: Phase 4
• Start date: July 4, 2017
• Est. completion date: September 1, 2019

Study information

• Verified date: February 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This study is designed to better understand the effect of a short course of antibiotics on changes in intestinal and nasopharyngeal microbiome on treated children and untreated household contacts. The investigators hypothesize that a short course of antibiotics will lead to decreased bacterial diversity shortly after completion of the antibiotic course, and higher probability of identification of bacterial resistance genes in rectal and nasopharyngeal samples. The investigators hypothesize that a 5-day course of antibiotics (azithromycin, amoxicillin, or co-trimoxazole) will lead to significantly decreased intestinal and nasopharyngeal bacterial diversity among children aged 6-59 months.

Specific Aim 1. Determine the effect of treatment with antibiotics on microbiome diversity in children aged 6-59 months following a 5-day course of antibiotics.

Specific Aim 1A. Determine the direct effect of a 5-day course of azithromycin, amoxicillin, or co-trimoxazole on intestinal and nasopharyngeal bacterial diversity in children aged 6-59 months compared to no treatment.

Specific Aim 1B. Determine the indirect effect of antibiotic treatment of children in a household on intestinal and nasopharyngeal bacterial diversity in an untreated child aged 6-59 months.

Specific Aim 1C. Assess the association between intestinal bacterial diversity and anthropometry in a population-based sample of children.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 252
• Est. completion date: September 1, 2019
• Est. primary completion date: September 1, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 59 Months

Eligibility

Inclusion Criteria:

• Households will be eligible for inclusion in the study if they have 2 or more children aged 6 months to 59 months currently residing in the household. Children from the household will be eligible if they are 6-59 months of age and are not currently receiving antibiotic treatment

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Child Development

Intervention

Drug:
• Azithromycin
Children in this arm will receive Azithromycin once a day.
• Amoxicillin
Children in this arm will receive Amoxicillin twice a day.
• Cotrimoxazole
Children in this arm will receive co-trimoxazole once a day.
• Placebo
Children in this arm will receive Placebo once a day.

Locations

Country	Name	City	State
Burkina Faso	Centre de Recherche en Santé de Nouna	Nouna
United States	UCSF Proctor Foundation	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	Centre de Recherche en Sante de Nouna, Burkina Faso, Heidelberg University

Countries where clinical trial is conducted

United States,  Burkina Faso, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Simpson's Index of Diversity (Alpha Diversity) in Intestinal Microbiome	The primary outcome of the study was pre-specified as a-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	Simpson's Index of Diversity (Alpha Diversity) in Microbiome	Direct and indirect effect of antibiotics on alpha diversity from rectal samples	Day 9
Secondary	Weight-for-height Z-score	Nutritional status as determined by weight-for-height Z-score vs. Placebo household Weight-for-height Z-score in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Weight-for-height Z (WHZ) scores were calculated based on the 2006 World Health Organization (WHO) standards. The mean of the 2006 population standards is 0. Lower standard deviations = worse outcomes. A cutoff of < -2 means moderately wasted (WHZ). A cutoff of < -3 means wasted (WHZ).	Day 35
Secondary	Height-for-age Z-score	Nutritional status as determined by height-for-age Z-score Height-for-age Z-score in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Height-for-age Z (HAZ) score were calculated based on the 2006 World Health Organization (WHO) standards. The mean of the 2006 population standards is 0. Lower standard deviations = worse outcomes. A cutoff of < -2 means moderately stunted (HAZ). A cutoff of < -3 means severely stunted (HAZ).	Day 35
Secondary	Weight-for-age Z-score	Nutritional status as determined by weight-for-age Z-score vs. Placebo household Weight-for-age Z-score in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Weight-for-age Z-score (WAZ) scores were calculated based on the 2006 World Health Organization (WHO) standards. The mean of the 2006 population standards is 0. Lower standard deviations = worse outcomes. A cutoff of < -2 means moderately underweight (WAZ). A cutoff of < -3 means severely underweight (WAZ).	Day 35
Secondary	Mid-upper Arm Circumference	Nutritional status as determined by mid-upper arm circumference in each antibiotic group compared with placebo 4 weeks after last antibiotic dose Mid-upper arm circumference (MUAC) in each antibiotic group compared with placebo 4 weeks after last antibiotic dose.; MUAC is a measure to assess nutritional status. It is measured on a straight left arm, mid-way between the tip of the shoulder and the tip of the elbow. It identifies acute malnutrition and is commonly used in children 6-59 months of age as well as pregnant women. MUAC less than 115 mm indicates severe wasting or severe acute malnutrition (SAM). MUAC greater than or equal to 115 mm and less than 125 mm indicates moderate wasting or moderate acute malnutrition (MAM).	Day 35
Secondary	Shannon's Index of Diversity (Alpha Diversity) in Intestinal Microbiome	Shannon's Alpha Diversity at Baseline and Post-treatment. combines richness and diversity. Shannon's index of diversity (alpha diversity) measures both the number of species and the inequality between species abundances. A large value is given by the presence of many species with well balanced abundances.	Baseline and Day 9 (Post- Treatment)
Secondary	Shannon's Index of Diversity (Alpha Diversity) in Nasopharyngeal Microbiome	Direct and indirect effects of antibiotics on Shannon's index of bacterial diversity	Day 9
Secondary	L1-norm Distance on Bacterial Reads (Intestinal)	L1-norm distance on bacterial reads (intestinal) - L1 norm is equivalent to Shannon's diversity. Shannon's Alpha Diversity combines richness and diversity. Shannon's index of diversity (alpha diversity) measures both the number of species and the inequality between species abundances. A large value is given by the presence of many species with well balanced abundances.	Baseline and Day 9 (Post- Treatment)
Secondary	L1-norm Distance on Bacterial Reads (Nasopharyngeal)	L1-norm distance on bacterial reads (nasopharyngeal)	Day 9
Secondary	L2-norm Distance on Bacterial Reads (Intestinal)	L2-norm distance on bacterial reads (intestinal) - L2 norm is equivalent to Simpson's diversity. 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 (Post- Treatment)
Secondary	L2-norm Distance on Bacterial Reads (Nasopharyngeal)	L2-norm distance on bacterial reads (nasopharyngeal)	Day 9
Secondary	Number of Participants With Macrolide Resistance Genes	Prevalence of macrolide resistance genes measured using DNA-seq from rectal swabs.	2 years
Secondary	Alpha Diversity in the Intestinal Microbiome	Alpha diversity in the intestinal microbiome using DNA-seq from rectal swabs	2 years