Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT02557425 |
Other study ID # |
1506994146 |
Secondary ID |
|
Status |
Completed |
Phase |
|
First received |
|
Last updated |
|
Start date |
October 2015 |
Est. completion date |
August 5, 2021 |
Study information
Verified date |
August 2021 |
Source |
Indiana University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
Each year, ~85.3 million pregnant women are at risk of becoming infected with Plasmodium
falciparum(1). Among women in sub-Saharan Africa, most of whom have some degree of clinical
immunity to malaria, malaria infection in pregnancy leads to placental malaria (PM), often
without clinical symptoms in the mother. The systemic and placental changes that occur with
malaria in pregnancy can adversely affect the developing fetal brain, an fetal brain injury
strongly affects long-term childhood neurodevelopmental (ND) and behavior but there are no
published studies to date on the impact of malaria in pregnancy on childhood ND. This study,
conducted in Uganda, will address the effects of malaria in pregnancy and childhood ND and
define mechanisms by which malaria may lead to ND impairment including micronutrient
deficiencies. ND outcomes will be measured by the following neuropsychological and behavioral
tests: Mullen Scales of Early Learning, the Color Object Association Test, the Early
Childhood Vigilance Test, the Behavior Rating Scales, the Behavior Related inventory of
Executive Function and the Child Behavior Checklist. These tests will be given at 12, 24, 36,
and 60 months of age. This study will be nested in an ongoing Ugandan IRB approved
interventional trial (PROMOTE-II) (NCT02163447). Blood sampling is being conducted in the
PROMOTE-II protocol for research purposes. Some of that blood will be used to test for
micronutrient deficiencies as well as other immune responses to malaria.
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.