About this trial
There are few safe, effective, and affordable interventions to improve pregnancy outcomes in low resource settings where the highest rates of poor birth outcomes occur. L-citrulline is naturally found in many foods and is changed into another important amino acid, L-arginine, in the body. L-arginine is important for the growth of a healthy placenta and healthy baby. Adding L-citrulline to the diets of pregnant women may be an effective and affordable way to improve the health of their babies.The goal of the AGREE trial is to test whether a dietary supplement containing a common food component, an amino acid called L-citrulline, can help pregnant Kenyan women at risk of malaria have healthier pregnancies and healthier babies. 2,960 pregnant Kenyan women will be enrolled and randomly assigned to take either a twice daily dietary supplement containing L-citrulline or a placebo supplement without additional L-citrulline. Maternal participants will be seen every month until delivery and at weeks 1 and 6 after birth. Infants will also be followed up at ages 6, 12, 18, and 24 months. The primary outcome of the study is 'adverse pregnancy outcome', a composite of foetal loss (miscarriage or still birth), preterm birth, low birth weight, small for gestational age or neonatal mortality. The results of the AGREE trial could help to guide obstetric and public health policy and provide a sustainable solution that could be implemented at the community level.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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,
Disqualifiers
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;
Trial design
Parallel
Treatments tested in this trial
L-citrulline
Dietary supplementTwice daily 6.0 g sachet, each containing 5.00 g of quality-assured L-citrulline powder, 0.66 g maltodextrin and 0.30 g lactose anhydrous, 0.03 g citric acid, 0.01 g lemon flavour + antenatal standard of care with enhanced monitoring
Treatment groups
Trial outcomes
Primary outcomes
Adverse pregnancy outcome
The primary outcome is 'adverse pregnancy outcome' defined as a composite of fetal loss (spontaneous abortion or stillbirth), singleton live births born SGA or with LBW, or preterm birth (PTB). 'Small for gestational age' will be defined using the INTERGROWTH population reference's 10th percentile. Fetal loss will be assessed monthly at scheduled ANC visits.
Secondary outcomes
Gestational hypertension
Assessed with systolic and diastolic blood pressure
Malaria infection during pregnancy
detected by microscopy and PCR (not for point of care) on peripheral blood
Placental malaria
detected by microscopy, by molecular methods, or by histology (past and active infection) on placental samples
Individual components of the placental malaria composite
detected by microscopy, by molecular methods, or by histology (past and active infection) on placental samples
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Liverpool School of Tropical Medicine
Lead sponsor
Kenya Medical Research Institute
Collaborator
University of Toronto
Collaborator
Telethon Kids Institute
Collaborator