L-citrulline supplementation during pregnancy to reduce adverse birth outcomes in Kenyan women at risk of malaria.
Oral Antenatal L-citrulline Supplementation to Reduce Adverse Pregnancy Outcomes: a Two-arm, Randomized, Placebo-controlled Multi-site Trial in Kenya
This trial will test whether taking a twice-daily L-citrulline supplement during pregnancy helps Kenyan women at risk of malaria have healthier pregnancies and babies.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 2960 (estimated) |
| Ages | 16 Years to 40 Years |
| Sex | Female |
| Sponsor | Liverpool School of Tropical Medicine Academic / other |
| Locations | 1 site (Kisumu) |
| Trial ID | NCT05934318 on ClinicalTrials.gov |
What this trial studies
AGREE is an individually randomized, two-arm, placebo-controlled trial enrolling 2,960 pregnant Kenyan women up to 24 weeks' gestation. Participants are randomly assigned to receive either a twice-daily 6.0 g sachet containing 5.00 g L-citrulline plus standard antenatal care or a taste-matched placebo sachet, with monthly visits through delivery. The primary outcome is a composite of fetal loss, preterm birth, small for gestational age, or low birthweight, and the trial includes safety monitoring and assessment of placental development. The trial targets women at high risk of malaria and protein undernutrition and requires ultrasound-confirmed singleton pregnancies and delivery at study clinics.
Who should consider this trial
Good fit: Pregnant women aged 16–40 with a viable singleton pregnancy up to 24 weeks' gestation, living in the study area and willing to attend monthly visits and deliver at a study clinic are ideal candidates.
Not a fit: Women with multiple pregnancies, pre-existing hypertension, renal disease, diabetes, severe anaemia, HIV positivity or unknown HIV status, lactose intolerance, inability to consent, or who cannot deliver at a study clinic are excluded and unlikely to benefit from this intervention.
Why it matters
Potential benefit: If successful, a low-cost L-citrulline supplement could lower rates of fetal loss, preterm birth, and low birthweight and improve newborn health in low-resource settings.
How similar studies have performed: Preclinical models have shown that L-arginine or citrulline improves placental development and pregnancy outcomes, while human data are limited but suggest potential benefit.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Pregnant women aged 16-40 years, * inclusive to 24 weeks gestational age as confirmed by ultrasound, * who have a viable singleton pregnancy, * are residents of the study area, * willing to adhere to scheduled and unscheduled study visit procedures, * willing to deliver in a study clinic or hospital Exclusion Criteria: * multiple pregnancies (i.e. twin/triplets); * pre-existing hypertension, renal disease and/or diabetes, or severe anaemia (Hb \< 5 g/dL); * HIV-positive or HIV status unknown; * malformations or nonviable pregnancy observed on enrolment ultrasound; * known allergy or contraindication to any of the study supplements including lactose intolerance or observing a lactose-free diet; * unable to give consent; or concurrent participation in any other clinical trial
Where this trial is running
Kisumu
- KEMRI Centre for Global Health Research — Kisumu, Kenya (Recruiting)
Study contacts
- Principal investigator: Kevin Kain, PhD — University of Toronto
- Study coordinator: Feiko O. ter Kuile, PhD
- Email: feiko.terkuile@lstmed.ac.uk
- Phone: +441517053287
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.