OPTIMAL LEAP: Optimizing Preventive Treatment Intervals for Malaria to Advance Longitudinal Learning, Executive Function, Attendance, and Pathways
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 1,500
- 主要终点
- Change from baseline to 24 months in NeuroScreen Executive Function Composite z-score
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 6 Years 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Monthly DP (Drug)
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.
干预措施: Quarterly DP (Drug)
结局指标
主要结局
Change from baseline to 24 months in NeuroScreen Executive Function Composite z-score
时间窗: 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.
次要结局
- 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)
- Change in Hemoglobin Concentration(Baseline and quarterly through 24 months)
- Incidence rate of symptomatic malaria episodes(Throughout 24 months)
- Change in inflammatory cytokine and chemokine concentrations(Baseline and quarterly through 24 months)
- Change in metabolomic and lipidomic pathway scores(Baseline and quarterly through 24 months)
- Prevalence and emergence of DP resistance-associated P. falciparum polymorphisms and copy number variants(Baseline through 24 months)
- Molecular force of infection(Baseline through 24 months)
- Complexity or multiplicity of infection at 12 and 24 months(12 and 24 months)
研究者
Megan Song McHenry
Associate Professor
Indiana University