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Pre-eclampsia (PE) complicates 2-8 % of pregnancies and is associated with high maternal and fetal morbidity and mortality. The early clinical manifestations are the occurrence of a maternal blood pressure and proteinuria. Placental dysfunction impairs the nutrient supply to the fetus, and may be the cause of an intrauterine growth retardation (IUGR). This is a disease that causes prematurity and currently the only known cure is delivery of the placenta. Nitrogen monoxide (NO) regulates the placental blood flow. However, pre-eclampsia is directly related to a failure of placental NO production. In this context, several clinical trials have tested the effect of NO donors such as L- arginine. However, supplementation with L -Arginine in a randomized trial in Nantes, has proved to be ineffective in severe vascular IUGR.
Citrulline is a natural aminoacid precursor to arginine and in contrast to L-arginine escapes uptake in the liver and appears directly in the peripheral blood converted by the kidney in arginine, released into the systemic circulation, Citrulline may therefore be more effective in the treatment of pre-eclampsia.
This prospective, randomized, comparative and double-blinded study aims to prolong pregnancy for patients with pre-eclampsia before 36 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L-Citrulline | Experimental | Bolus (9g) after patient stabilization, then 3g 3 times a day until delivery |
|
| Lactose | Placebo Comparator | Bolus (9g) after patient stabilization, then 3g 3 times a day until delivery |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Citrulline | Drug | Citrulline supplementation |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| number of days between the therapeutic initiation and childbirth | childbirth |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nobert Winer, Dr | Nantes University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU de Nantes | Nantes | 44093 | France | |||
| Hôpital Cochin (Maternité Port-Royal) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39638148 | Derived | Winer N, Misbert E, Masson D, Girault A, Alexandre-Gouabau MC, Ducarme G, Dochez V, Thubert T, Boivin M, Ferchaud-Roucher V, Pere M, Darmaun D. Oral citrulline supplementation in pregnancies with preeclampsia: a multicenter, randomized, double-blind clinical trial. Am J Clin Nutr. 2025 Feb;121(2):488-496. doi: 10.1016/j.ajcnut.2024.12.001. Epub 2024 Dec 9. |
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| ID | Term |
|---|---|
| D011225 | Pre-Eclampsia |
| ID | Term |
|---|---|
| D046110 | Hypertension, Pregnancy-Induced |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D002956 | Citrulline |
| ID | Term |
|---|---|
| D000599 | Amino Acids, Diamino |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Drug |
Placebo |
|
| Paris |
| 75014 |
| France |