- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02557425
Prophylaxis Against Malaria to Enhance Child Development (PROTECT Study) (PROTECT)
Prophylaxis Against Malaria to Enhance Child Development
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The PROMOTE-II randomized clinical trial in Tororo, Uganda, led by investigators from Makerere University in Uganda and the University of California-San Francisco (UCSF), provides an ideal setting to assess the effects of malaria prevention in pregnant women and their children on childhood ND. In PROMOTE-II Project 1,300 pregnant HIV-uninfected women will be randomized at 12-20 weeks of gestation to malaria prophylaxis with 3 doses of sulfadoxine-pyrimethamine (current standard of care), 3 doses of dihydroartemisinin-piperaquine (DP), or monthly DP. Their children will be randomized to receive DP prophylaxis monthly or every 3 months from 2 to 24 months age. The children will be followed for malaria episodes from birth to age 36 months. The proposed prospective study of child ND, the Prophylaxis against malaria To Enhance Child developmenT (PROTECT) study, will be nested within the PROMOTE-II Project 1 cohort. It is hypothesized that mothers on SP and mothers and children on less frequent prophylaxis will have more malaria episodes. The investigators predict that child ND will improve with more effective prophylaxis.
The central hypotheses of this study are that malaria prevention in pregnant women and their children improves child ND through 1) prevention of placental sequestration and inflammation and of consequent micronutrient deficiency in the fetus, and 2) reduction of systemic inflammation and endothelial activation that can lead to micronutrient deficiency and anemia during pregnancy and in early childhood and thus to alteration of brain structures particularly sensitive to such deficiencies (e.g., the hippocampus, myelin and the frontal lobe). The collaborative team, which has expertise in malaria in pregnant women and children, malaria pathogenesis, micronutrient deficiency, fetal and child neurodevelopment, and modeling of complex disease pathways, is well qualified to undertake the proposed research.
The specific aims of the study are:
Aim 1. Determine the effect of malaria prevention in pregnant women and their children on child ND. Hypotheses: 1) Long-term child ND improves with more effective chemoprevention in pregnant women and in their children. 2) The effect of malaria prevention on child ND persists through 36 months of age. Child ND will be assessed with a testing battery validated in previous studies by this group in Ugandan children. The investigators will test these hypotheses by comparing child ND at 12, 24, 36 and 60 months of age between treatment groups.
Aim 2. Identify the major mechanisms by which malaria prevention in pregnant women and children affects child ND. Hypotheses: 1) Malaria prevention in pregnant women affects child ND through prevention of placental sequestration and inflammation, with consequent prevention of prematurity, intrauterine growth retardation and fetal micronutrient deficiency. 2) Malaria prevention in pregnant women and in their children after birth improves child ND through reduction of systemic inflammation, endothelial activation, micronutrient deficiency and anemia, but the relative contributions of the factors differ in pregnant women compared to children. The investigators will test these hypotheses by conducting path analysis to determine if networks that include these paths explain a significant proportion of the difference in child ND between treatment groups.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Tororo, Uganda
- Tororo District Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Enrolled in Makerere University-UCSF PROMOTE II study
- HIV-uninfected
- 12 months of age at the time of enrollment
- Within 30 km of the clinic
Exclusion Criteria:
- Serious adverse event to the study drugs requiring cessation of study drug
- Active illness at enrollment (child can be enrolled once active illness has been treated and they are back to baseline health)
- Previous history of head trauma or coma in the child
- Cerebral palsy or other severe neurologic disease
- Known chronic illness requiring medical care
- Major medical abnormalities on screening history of past health
- Known developmental delay
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Maternal SP/Child 3mo DP
In this group in the PROMOTE-II study, mothers receive 3 doses of sulfadoxine-pyrimethamine (SP), and children receive every 3 month dihydroartemisinin-piperaquine (DP).
No intervention is given in the observational PROTECT study.
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Maternal 3 dose DP/Child 3mo DP
In this group in the PROMOTE-II study, mothers receive 3 doses of DP, and children receive every 3 month DP.No intervention is given in the observational PROTECT study.
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Maternal 3 dose DP/Child monthly DP
In this group in the PROMOTE-II study, mothers receive 3 doses of DP, and children receive monthly DP.
No intervention is given in the observational PROTECT study.
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Maternal monthly DP/Child 3mo DP
In this group in the PROMOTE-II study, mothers receive monthly DP, and children receive every 3 month DP.
No intervention is given in the observational PROTECT study.
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Maternal monthly DP/child monthly DP
In this group in the PROMOTE-II study, mothers receive monthly DP, and children receive every monthly DP.
No intervention is given in the observational PROTECT study.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Z-scores for Overall cognitive ability
Time Frame: 12 months of age
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12 months of age
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Z-scores for Overall cognitive ability
Time Frame: 24 months of age
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24 months of age
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Z-scores for Overall cognitive ability
Time Frame: 36 months of age
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36 months of age
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Z scores for Elicited Imitation
Time Frame: 12 months of age
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12 months of age
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Z scores for Elicited Imitation
Time Frame: 24 months of age
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24 months of age
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Z scores for Elicited Imitation
Time Frame: 36 months of age
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36 months of age
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Z scores of Overal Cognitive ability
Time Frame: 60 months of age
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60 months of age
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Z scores of Elicited Imitation
Time Frame: 60 months of age
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60 months of age
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Z scores for Behavioral Rating Scale
Time Frame: 24, 36, and 60 months of age
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24, 36, and 60 months of age
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Z scores for Behavior Related Inventory of Executive Function (BRIEF)
Time Frame: 24, 36, and 60 months of age
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24, 36, and 60 months of age
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Z scores for Child Behavior Checklist (CBCL)
Time Frame: 24, 36, and 60 months of age
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24, 36, and 60 months of age
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Chandy C John, MD, Indiana University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1506994146
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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