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

27 sierpnia 2026 zaktualizowane przez: Megan Song McHenry, Indiana University

OPTIMAL LEAP: Optimizing Preventive Treatment Intervals for Malaria to Advance Longitudinal Learning, Executive Function, Attendance, and Pathways

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.

Przegląd badań

Status

Jeszcze nie rekrutacja

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Szacowany)

1500

Faza

  • Faza 3

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Kontakt w sprawie studiów

  • Nazwa: Kristen Cunningham, MPH, MS
  • Numer telefonu: 317-278-5675
  • E-mail: kricunn@iu.edu

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

  • Dziecko

Akceptuje zdrowych ochotników

Tak

Opis

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Zapobieganie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Pojedynczy

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Monthly Dihydroartemisinin-piperaquine (DP) IPTsc
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.
Lek: Monthly DP
Age- or weight-based dihydroartemisinin-piperaquine administered monthly for 24 months as intermittent preventive treatment in school-aged children (IPTsc).
Aktywny komparator: Quarterly DP IPTsc
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.
Lek: Quarterly DP
Age- or weight-based dihydroartemisinin-piperaquine administered every three months for 24 months as intermittent preventive treatment in school-aged children (IPTsc).

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Change from baseline to 24 months in NeuroScreen Executive Function Composite z-score
Ramy czasowe: Baseline through 24 months
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

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Change from baseline to 24 months in EGRA score
Ramy czasowe: Baseline, 12 months, and 24 months
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.
Baseline, 12 months, and 24 months
Change from baseline to 24 months in EGMA score
Ramy czasowe: Baseline, 12 months, and 24 months
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.
Baseline, 12 months, and 24 months
Total School Absenteeism
Ramy czasowe: Throughout 24 months of follow-up
Number and proportion of enrolled school days missed during the 24-month follow-up period, based on school registers and teacher confirmation.
Throughout 24 months of follow-up
Malaria-Associated School Absenteeism
Ramy czasowe: Throughout 24 months of follow-up
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.
Throughout 24 months of follow-up
Prevalence of qPCR-detectable P. falciparum parasitemia
Ramy czasowe: Baseline and quarterly through 24 months
Presence of P. falciparum infection measured by qPCR, with microscopy used to identify patent infections
Baseline and quarterly through 24 months
Change in Hemoglobin Concentration
Ramy czasowe: Baseline and quarterly through 24 months
Hemoglobin concentration measured in g/dL at baseline and quarterly through 24 months.
Baseline and quarterly through 24 months
Incidence rate of symptomatic malaria episodes
Ramy czasowe: Throughout 24 months
Number of symptomatic malaria episodes per child-year during follow-up.
Throughout 24 months
Change in inflammatory cytokine and chemokine concentrations
Ramy czasowe: Baseline and quarterly through 24 months
Longitudinal changes in log-transformed inflammatory biomarker concentrations, including cytokines and chemokines implicated in malaria-associated cognitive outcomes.
Baseline and quarterly through 24 months
Change in metabolomic and lipidomic pathway scores
Ramy czasowe: Baseline and quarterly through 24 months
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.
Baseline and quarterly through 24 months
Prevalence and emergence of DP resistance-associated P. falciparum polymorphisms and copy number variants
Ramy czasowe: Baseline through 24 months
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.
Baseline through 24 months
Molecular force of infection
Ramy czasowe: Baseline through 24 months
Acquisition of new genetically distinct P. falciparum clones over time as determined by parasite diversity genotyping.
Baseline through 24 months
Complexity or multiplicity of infection at 12 and 24 months
Ramy czasowe: 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.
12 and 24 months

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Indiana University

Współpracownicy

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

Śledczy

  • Główny śledczy: Megan S McHenry, MD, MS, Indiana University
  • Główny śledczy: Eren Oyungu, MBChB, MMED, Moi University

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Szacowany)

1 stycznia 2028

Zakończenie podstawowe (Szacowany)

1 stycznia 2030

Ukończenie studiów (Szacowany)

1 stycznia 2033

Daty rejestracji na studia

Pierwszy przesłany

27 sierpnia 2026

Pierwszy przesłany, który spełnia kryteria kontroli jakości

27 sierpnia 2026

Pierwszy wysłany (Rzeczywisty)

1 września 2026

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

1 września 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

27 sierpnia 2026

Ostatnia weryfikacja

1 sierpnia 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • Optimal Leap

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

TAK

Opis planu IPD

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.

Ramy czasowe udostępniania IPD

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.

Kryteria dostępu do udostępniania IPD

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.

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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