A Phase 3 interventional study of Monthly DP and Quarterly DP in Malaria, Asymptomatic Malaria and Intermittent Preventive Treatment, sponsored by Indiana University. Not yet recruiting. Open to participants aged 6 Years to 10 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-01.
Sponsored by Indiana University · Phase 3, Interventional, and Prevention
Malaria remains a major cause of illness among school-aged children in sub-Saharan Africa, many of whom carry asymptomatic Plasmodium falciparum infections that may contribute to anemia, inflammation, school absenteeism, and impaired cognitive performance. Intermittent preventive treatment in school-aged children (IPTsc) is recommended by the World Health Organization in settings with moderate-to-high malaria transmission, but the optimal dosing frequency remains uncertain. This cluster-randomized trial will compare monthly versus quarterly administration of dihydroartemisinin-piperaquine (DP) among 1,500 children aged 6-10 years attending six primary schools in Siaya County, Kenya. The primary objective is to determine whether monthly IPTsc results in greater improvements in executive functioning compared with quarterly IPTsc. Secondary objectives include evaluating effects on literacy, numeracy, school attendance, malaria infection, anemia, inflammatory and metabolic biomarkers, and molecular markers of antimalarial resistance.
Malaria remains a leading cause of morbidity in sub-Saharan Africa, and school-aged children represent an important reservoir of asymptomatic Plasmodium falciparum infection. Although often clinically silent, persistent low-density infections have been associated with anemia, immune activation, school absenteeism, and impaired executive functioning, including working memory, inhibitory control, and cognitive flexibility. These cognitive processes are critical for learning, academic achievement, and long-term educational attainment.
The World Health Organization recommends intermittent preventive treatment for school-aged children (IPTsc) in settings with moderate-to-high malaria transmission; however, evidence is limited regarding the optimal frequency of preventive treatment. Dihydroartemisinin-piperaquine (DP) provides extended post-treatment prophylaxis and is a promising IPTsc regimen, but more frequent administration may also increase drug selection pressure and contribute to the emergence of antimalarial resistance.
This study is a two-arm, school-cluster randomized trial conducted in six primary schools in Siaya County, Kenya. A total of 1,500 children aged 6 to 10 years will be enrolled and followed for 24 months. Enrollment will be balanced across one-year age bands, with approximately 300 children per age band at baseline. Schools will be randomized to receive either monthly DP IPTsc or quarterly DP IPTsc. The primary outcome is change in executive functioning measured using the tablet-based NeuroScreen assessment platform. Secondary outcomes include literacy and numeracy performance measured using the Early Grade Reading Assessment (EGRA) and Early Grade Mathematics Assessment (EGMA), school attendance, malaria-associated absenteeism, P. falciparum parasitemia, hemoglobin levels, symptomatic malaria episodes, inflammatory biomarkers, metabolomic profiles, and molecular markers of antimalarial resistance.
The study will also investigate biological mechanisms linking asymptomatic malaria infection with cognitive outcomes. Longitudinal assessments of parasitemia, inflammatory cytokines and chemokines, metabolomic pathways, and genetic markers of parasite resistance will be performed. Resistance surveillance will include evaluation of kelch13, pfcrt, pfmdr1, pfexo, and pfplasmepsin II/III markers. Findings from this trial will provide evidence on the benefits and risks of different IPTsc dosing schedules and inform malaria prevention policies aimed at improving child health, educational achievement, and long-term developmental outcomes while minimizing the risk of antimalarial resistance.
Exclusion Criteria:
Participants enrolled in schools randomized to the monthly intervention arm will receive age- or weight-basedtherapeutic course of dihydroartemisinin-piperaquine, according to protocol-defined dosing procedures, administered monthly for 24 months through a school-based intermittent preventive treatment program. Dosing will be directly observed by study staff when administered at school; make-up dosing procedures will be used for children absent on scheduled dosing days according to the protocol.
Drug: Monthly DP
Participants enrolled in schools randomized to the quarterly intervention arm will receive age- or weight-based therapeutic course of dihydroartemisinin-piperaquine, according to protocol-defined, dosing procedures administered every three months for 24 months through a school-based intermittent preventive treatment program. Dosing will be directly observed by study staff when administered at school; make-up dosing procedures will be used for children absent on scheduled dosing days according to the protocol.
Drug: Quarterly DP
Age- or weight-based dihydroartemisinin-piperaquine administered monthly for 24 months as intermittent preventive treatment in school-aged children (IPTsc).
Age- or weight-based dihydroartemisinin-piperaquine administered every three months for 24 months as intermittent preventive treatment in school-aged children (IPTsc).
Change from baseline to 24 months in NeuroScreen Executive Function Composite z-score
Executive function will be assessed quarterly using tablet-based NeuroScreen tasks measuring working memory, inhibitory control/attention, and cognitive flexibility. The primary endpoint will be the adjusted change in the EF composite z-score from baseline to 24 months. Higher scores indicate better performance.
Time frame: Baseline through 24 months
Change from baseline to 24 months in EGRA score
Literacy will be assessed using Early Grade Reading Assessment subtests adapted for the local language and educational context. Scores will be analyzed as standardized continuous outcomes; higher scores indicate better reading performance.
Time frame: Baseline, 12 months, and 24 months
Change from baseline to 24 months in EGMA score
Numeracy will be assessed using Early Grade Mathematics Assessment subtests adapted for the local educational context. Scores will be analyzed as standardized continuous outcomes; higher scores indicate better mathematics performance.
Time frame: Baseline, 12 months, and 24 months
Total School Absenteeism
Number and proportion of enrolled school days missed during the 24-month follow-up period, based on school registers and teacher confirmation.
Time frame: Throughout 24 months of follow-up
Malaria-Associated School Absenteeism
Number of school days missed due to suspected or confirmed malaria illness, based on study assessments, clinic records when available, and caregiver/teacher illness reports.
Time frame: Throughout 24 months of follow-up
Prevalence of qPCR-detectable P. falciparum parasitemia
Presence of P. falciparum infection measured by qPCR, with microscopy used to identify patent infections
Time frame: Baseline and quarterly through 24 months
Change in Hemoglobin Concentration
Hemoglobin concentration measured in g/dL at baseline and quarterly through 24 months.
Time frame: Baseline and quarterly through 24 months
Incidence rate of symptomatic malaria episodes
Number of symptomatic malaria episodes per child-year during follow-up.
Time frame: Throughout 24 months
Change in inflammatory cytokine and chemokine concentrations
Longitudinal changes in log-transformed inflammatory biomarker concentrations, including cytokines and chemokines implicated in malaria-associated cognitive outcomes.
Time frame: Baseline and quarterly through 24 months
Change in metabolomic and lipidomic pathway scores
Longitudinal changes in prespecified metabolomic and lipidomic pathways related to inflammation, oxidative stress, mitochondrial energy metabolism, lipid-mediated inflammation, tryptophan-kynurenine metabolism, and iron handling. Analyses may be conducted in a prespecified longitudinal subset, with targeted validation in the broader cohort.
Time frame: Baseline and quarterly through 24 months
Prevalence and emergence of DP resistance-associated P. falciparum polymorphisms and copy number variants
Molecular surveillance will assess resistance-associated markers including kelch13, pfcrt, pfmdr1, pfexo, and pfplasmepsin II/III copy number variation. Sequence variants will be assessed using multiplex amplicon sequencing, and copy number variation will be confirmed by qPCR or ddPCR when appropriate.
Time frame: Baseline through 24 months
Molecular force of infection
Acquisition of new genetically distinct P. falciparum clones over time as determined by parasite diversity genotyping.
Time frame: Baseline through 24 months
Complexity or multiplicity of infection at 12 and 24 months
Complexity/multiplicity of infection will be estimated from parasite diversity markers to quantify the number of genetically distinct parasite clones within infections and compare differential protection conferred by monthly versus quarterly IPTsc.
Time frame: 12 and 24 months
No study locations are listed for this record.
Plan to share: Yes — De-identified participant-level data underlying published results, including demographic variables, NeuroScreen EF scores, EGRA/EGMA scores, attendance outcomes, malaria testing results, hemoglobin, inflammatory biomarker data, processed metabolomic pathway data, and processed parasite genotyping/resistance-marker data, as appropriate. Supporting documents: Study protocol, statistical analysis plan, informed consent form as appropriate, data dictionary, analytic code, and assay metadata. Timing: Data supporting primary publications will be made available at the time of publication or by the end of the award period, consistent with NIH and repository requirements. Access criteria: Data will be de-identified before sharing. More granular child-level, school-linked, geospatial, or sensitive data may be shared through controlled-access mechanisms to protect children, families, schools, and communities.
This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Indiana University