OPTIMAL LEAP: Optimizing Dihydroartemisinin-Piperaquine IPTsc Intervals to Advance Learning, Executive Function, Attendance, and Antimalarial Resistance Surveillance in Kenyan Schoolchildren

NCT07798583 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: Optimal Leap
• Study Type: interventional
• Target: 1,500
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Malaria; Asymptomatic Malaria; Intermittent Preventive Treatment

Keywords

Malaria; Plasmodium falciparum; Asymptomatic; Anemia; Cognition; School-aged Children; Intermittent preventive treatment; IPTsc; Dihydroartemisinin-piperaquine; Executive function; Literacy; Numeracy; School attendance; Antimalarial resistance; Inflammation; Metabolomics; Kenya

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline through 24 months

Secondary Outcomes (12)

• Change from baseline to 24 months in EGRA score

  Baseline, 12 months, and 24 months

• Change from baseline to 24 months in EGMA score

  Baseline, 12 months, and 24 months

• Total School Absenteeism

  Throughout 24 months of follow-up

• Malaria-Associated School Absenteeism

  Throughout 24 months of follow-up

• Prevalence of qPCR-detectable P. falciparum parasitemia

  Baseline and quarterly through 24 months

Study Arms (2)

Monthly Dihydroartemisinin-piperaquine (DP) IPTsc

EXPERIMENTAL

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

Quarterly DP IPTsc

ACTIVE COMPARATOR

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

Interventions

Monthly DP DRUG

Age- or weight-based dihydroartemisinin-piperaquine administered monthly for 24 months as intermittent preventive treatment in school-aged children (IPTsc).

Monthly Dihydroartemisinin-piperaquine (DP) IPTsc

Quarterly DP DRUG

Age- or weight-based dihydroartemisinin-piperaquine administered every three months for 24 months as intermittent preventive treatment in school-aged children (IPTsc).

Quarterly DP IPTsc

Eligibility Criteria

• Age: 6 Years - 10 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Age 6 to 10 years at enrollment
• Enrollment in a participating primary school in Siaya County, Kenya
• Residence within the participating school's catchment area with no plans to relocate during the study period
• Parent or legal guardian able and willing to provide informed consent
• Child able and willing to provide assent, as applicable according to local regulations and age requirements
• Willingness to comply with study procedures and follow-up visits

You may not qualify if:

• Known hypersensitivity or contraindication to dihydroartemisinin-piperaquine (DP)
• Severe acute illness requiring urgent medical evaluation or hospitalization at enrollment
• Known cardiac disease or history of conditions associated with increased risk of QT prolongation
• Severe malnutrition requiring urgent referral or treatment
• Recent antimalarial treatment within the protocol-defined washout period
• Severe anemia (hemoglobin \<7 g/dL) at screening
• Measured fever (≥38.0°C) or acute febrile illness requiring evaluation at screening
• Any medical, social, or behavioral condition that, in the opinion of the investigators, would make participation unsafe or interfere with study participation or interpretation of study results

Sponsors & Collaborators

• Indiana University: lead
• Jaramogi Oginga Odinga University of Science and Technology: collaborator
• Harvard School of Public Health (HSPH): collaborator
• Broad Institute of MIT and Harvard: collaborator
• KEMRI Centre for Global Health Research (CGHR), Kisumu, Kenya: collaborator

Related Publications (9)

• McHenry MS, Ayodo G, Marete I, Hasund CM, Knight V, Cunningham KB, Gaskin EL, White G, Tu W, Neafsey DE, John CC, Tran TM. Association of asymptomatic Plasmodium falciparum infections and its treatment with short-term cognitive performance in school-aged children: a prospective cohort study in western Kenya. J Infect. 2026 Aug 19:106831. doi: 10.1016/j.jinf.2026.106831. Online ahead of print.

  PMID: 42617751 BACKGROUND

• Kane J, Li X, Kumar S, Button-Simons KA, Brenneman KMV, Dahlhoff H, Sievert MAC, Checkley LA, Shoue DA, Singh PP, Abatiyow BA, Haile MT, Nair S, Reyes A, Tripura R, Peto T, Lek D, Kappe SHI, Dhorda M, Nkhoma SC, Cheeseman IH, Vaughan AM, Anderson TJC, Ferdig MT. A Plasmodium falciparum genetic cross reveals the contributions of pfcrt and plasmepsin II/III to piperaquine drug resistance. bioRxiv [Preprint]. 2023 Sep 17:2023.06.06.543862. doi: 10.1101/2023.06.06.543862.

  PMID: 37745488 BACKGROUND

• Amato R, Lim P, Miotto O, Amaratunga C, Dek D, Pearson RD, Almagro-Garcia J, Neal AT, Sreng S, Suon S, Drury E, Jyothi D, Stalker J, Kwiatkowski DP, Fairhurst RM. Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study. Lancet Infect Dis. 2017 Feb;17(2):164-173. doi: 10.1016/S1473-3099(16)30409-1. Epub 2016 Nov 3.

  PMID: 27818095 BACKGROUND

• McHenry MS, Mukherjee D, Bhavnani S, Kirolos A, Piper JD, Crespo-Llado MM, Gladstone MJ. The current landscape and future of tablet-based cognitive assessments for children in low-resourced settings. PLOS Digit Health. 2023 Feb 23;2(2):e0000196. doi: 10.1371/journal.pdig.0000196. eCollection 2023 Feb.

  PMID: 36821551 BACKGROUND

• Andrade CM, Fleckenstein H, Thomson-Luque R, Doumbo S, Lima NF, Anderson C, Hibbert J, Hopp CS, Tran TM, Li S, Niangaly M, Cisse H, Doumtabe D, Skinner J, Sturdevant D, Ricklefs S, Virtaneva K, Asghar M, Homann MV, Turner L, Martins J, Allman EL, N'Dri ME, Winkler V, Llinas M, Lavazec C, Martens C, Farnert A, Kayentao K, Ongoiba A, Lavstsen T, Osorio NS, Otto TD, Recker M, Traore B, Crompton PD, Portugal S. Increased circulation time of Plasmodium falciparum underlies persistent asymptomatic infection in the dry season. Nat Med. 2020 Dec;26(12):1929-1940. doi: 10.1038/s41591-020-1084-0. Epub 2020 Oct 26.

  PMID: 33106664 BACKGROUND

• Salgado C, Ayodo G, Macklin MD, Gould MP, Nallandhighal S, Odhiambo EO, Obala A, O'Meara WP, John CC, Tran TM. The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya. Malar J. 2021 Sep 17;20(1):371. doi: 10.1186/s12936-021-03905-w.

  PMID: 34535134 BACKGROUND

• Cohee LM, Opondo C, Clarke SE, Halliday KE, Cano J, Shipper AG, Barger-Kamate B, Djimde A, Diarra S, Dokras A, Kamya MR, Lutumba P, Ly AB, Nankabirwa JI, Njagi JK, Maiga H, Maiteki-Sebuguzi C, Matangila J, Okello G, Rohner F, Roschnik N, Rouhani S, Sissoko MS, Staedke SG, Thera MA, Turner EL, Van Geertruyden JP, Zimmerman MB, Jukes MCH, Brooker SJ, Allen E, Laufer MK, Chico RM. Preventive malaria treatment among school-aged children in sub-Saharan Africa: a systematic review and meta-analyses. Lancet Glob Health. 2020 Dec;8(12):e1499-e1511. doi: 10.1016/S2214-109X(20)30325-9. Epub 2020 Oct 22.

  PMID: 33222799 BACKGROUND

• Clarke SE, Jukes MC, Njagi JK, Khasakhala L, Cundill B, Otido J, Crudder C, Estambale BB, Brooker S. Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial. Lancet. 2008 Jul 12;372(9633):127-138. doi: 10.1016/S0140-6736(08)61034-X.

  PMID: 18620950 BACKGROUND

• Johnson AE, Upadhye A, Knight V, Gaskin EL, Turnbull LB, Ayuku D, Nyalumbe M, Abuonji E, John CC, McHenry MS, Tran TM, Ayodo G. Subclinical Inflammation in Asymptomatic Schoolchildren With Plasmodium falciparum Parasitemia Correlates With Impaired Cognition. J Pediatric Infect Dis Soc. 2024 May 30;13(5):288-296. doi: 10.1093/jpids/piae025.

  PMID: 38512283 BACKGROUND

MeSH Terms

Conditions

Malaria; Malaria, Falciparum; Anemia; Literacy; Inflammation

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Communication; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Megan S McHenry, MD, MS

  Indiana University

  PRINCIPAL INVESTIGATOR

• Eren Oyungu, MBChB, MMED

  Moi University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristen Cunningham, MPH, MS

CONTACT

317-278-5675; kricunn@iu.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assessors for NeuroScreen, EGRA, and EGMA and laboratory personnel will be masked to school allocation when feasible; participants and intervention staff cannot be masked due to dosing schedule differences.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Outcome assessors for NeuroScreen, EGRA, and EGMA and laboratory personnel will be masked to school allocation when feasible; participants and intervention staff cannot be masked due to dosing schedule differences.

Study Record Dates

• First Submitted: August 27, 2026
• First Posted: September 1, 2026
• Study Start (Estimated): January 1, 2028
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2033
• Last Updated: September 1, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will become available within 12 months of publication of the primary study results and will remain available for at least 5 years following publication.
• Access Criteria: Access to de-identified quantitative data will require submission of a data request, approval by the study investigators, execution of an appropriate data use agreement, and compliance with applicable institutional, U.S., and Kenyan regulations governing human subjects research and data sharing.