MORDOR II Burkina Faso: Longitudinal Trial (GAMIN)
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|ClinicalTrials.gov Identifier: NCT03676751|
Recruitment Status : Not yet recruiting
First Posted : September 19, 2018
Last Update Posted : September 4, 2019
Globally, childhood mortality has shown a promising downward trend in recent years, however, many sub-Saharan countries still have relatively high child mortality rates. In previous studies within Niger, Tanzania, and Malawi, mass azithromycin treatment to children aged 1-59 months old effectively reduced all-cause childhood mortality. A similar study will be conducted in Burkina Faso to replicate the results of mass azithromycin treatment.
The investigators propose an individually randomized placebo-controlled trial alongside the MORDOR II Burkina Faso trial to evaluate the effect of a single dose of azithromycin (20 mg/kg) on potential mediators of the effect of azithromycin on all-cause mortality. Many questions surround the mechanism behind azithromycin's effect on reducing childhood mortality. Further questions exist regarding antibiotic resistance and how mass antibiotic administration can impact intestinal microflora. The goal of this study is to demonstrate the changes in the gut microbiome after antibiotic administration and to measure the growth of children after receiving a single dose of azithromycin. Additionally we will measure resistance markers, inflammatory markers, and IgA-bound bacteria. We hypothesize that a single dose of azithromycin will lead to a significant increase in child growth and that the gut microbiome will be significantly different in children who received azithromycin compared to those who received placebo.
- . To determine the effect of a single dose of azithromycin for children aged 8 days-59 months on longitudinal changes in the intestinal microbiome over a 6-month period. We hypothesize that a single dose of azithromycin will result in a significant difference in the intestinal microbiome within the treatment group compared to the placebo group after a 6-month period within children ages 8 days-59 months.
- . To determine the effect of a single dose of azithromycin for children aged 8 days-59 months on child growth over a 6-month period. We hypothesize that a single dose of azithromycin will increase child growth over a 6-month period in children aged 8 days-59 months.
- . To determine the effect of a single dose of azithromycin for children aged 8 days to 59 months on the presence of macrolide genetic resistance determinants within the first two weeks post-treatment. The investigators hypothesize that a single dose of azithromycin will increase the presence of macrolide resistance determinants over a 2 week period in children aged 8 days to 59 months.
The study will be conducted in Nouna Town in northwestern Burkina Faso.
|Condition or disease||Intervention/treatment||Phase|
|Child Growth Diversity of Microbiome Child Mortality Resistance Bacterial||Drug: Azithromycin Drug: Placebo||Phase 4|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||500 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Individually randomized placebo-controlled trail of azithromycin vs. placebo to establish the efficacy and safety of azithromycin.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Quadruple: (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Gut and Azithromycin Mechanisms in Infants and Neonates|
|Estimated Study Start Date :||September 17, 2019|
|Estimated Primary Completion Date :||July 1, 2020|
|Estimated Study Completion Date :||August 1, 2022|
Active Comparator: Azithromycin
A single dose of azithromycin will be administered to children between the ages of 8 days and 59 months old.
Zithromax® for oral suspension is supplied in bottles containing azithromycin dehydrate powder equivalent to 1200mg per bottle and the following inactive ingredients: sucrose; tribasic anhydrous sodium phosphate; hydroxypropyl cellulose; xanthan gum; FD&C Red #40; and flavoring including spray dried artificial cherry, crème de vanilla, and banana. After constitution, a 5mL suspension contains 200mg of azithromycin.
Placebo Comparator: Placebo
A single dose of placebo will be administered to children between the ages of 8 days and 59 months old.
Oral suspension of placebo for azithromycin
- Intestinal microbial diversity [ Time Frame: 6 months ]Simpson's diversity estimated from next generation sequencing
- Macrolide Resistance [ Time Frame: 2 weeks ]Presence of macrolide genetic resistance determinants measured using DNA-seq from rectal swabs from 50 children
- Change in weight over time [ Time Frame: 180 days post-treatment ]WAZ. Weight will be measured at all follow-ups and weight-for-age z-scores will be calculated. Weight measured in g/kg/day.
- Change in height over time [ Time Frame: 180 days post-treatment ]Height or length will be measured at all follow-ups and height-for-age z-scores will be calculated.
- Proportion of infants developing infantile hypertrophic pyloric stenosis [ Time Frame: 6 months ]
- Mortality [ Time Frame: 180 days post-treatment ]Vital status will be assessed at all follow-up time points. Mortality will be defined as death within the study period. Date of death will be collected.
- Malaria status [ Time Frame: 180 days post-treatment ]Blood smears (thin and thick) for malaria will be collected at all follow-ups to determine malaria infection status.
- Adverse Events [ Time Frame: 180 days post-treatment ]Caregivers will be asked if the child has been taken to the health post since the last visit and why
- Genotypic resistance [ Time Frame: 180 days post-treatment ]Measured with targeted PCR
- Inflammatory marker changes [ Time Frame: 6 months ]Measured by C-reactive protein
- IgA-bound bacteria from small intestine changes [ Time Frame: 180 days post-treatment ]Measured using BugFACS from whole blood and stool
- Nutritional status [ Time Frame: 180 days post-treatment ]To be measured using mid-upper arm circumference
- Acute modulation of the gut microbiome [ Time Frame: 2 weeks post-treatment ]Next generation sequencing
- L-1 norm distance on bacterial reads (intestinal) [ Time Frame: 2 weeks post-treatment ]L-1 norm distance on bacterial reads (intestinal) from rectal swabs of 50 children
- L-2 norm distance on bacterial reads (intestinal) [ Time Frame: 2 weeks post-treatment ]L-2 norm distance on bacterial reads (intestinal) from rectal swabs of 50 children
- Changes in normalized reads for Campylobacter species [ Time Frame: 2 weeks post-treatment ]Changes in normalized reads for Campylobacter species using DNA-seq from rectal swabs of 50 children
- Resistome [ Time Frame: 2 weeks post-treatment ]Chao1 total resistance gene determinant richness using DNA-seq from rectal swabs of 50 children
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03676751
|Contact: Tom Lietman, MDemail@example.com|
|Contact: Jessica Brogdon, MPHfirstname.lastname@example.org|
|Principal Investigator:||Catherine Oldenburg, PhD||University of California, San Francisco|
|Principal Investigator:||Ali Sie, MD, PhD||Centre de Recherce en Sante de Nouna|
|Principal Investigator:||Tom Lietman, MD||University of California, San Francisco|