NCT02801695

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
116

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Feb 2017

Typical duration for phase_2

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 3, 2016

Completed
13 days until next milestone

First Posted

Study publicly available on registry

June 16, 2016

Completed
8 months until next milestone

Study Start

First participant enrolled

February 20, 2017

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2020

Completed
Last Updated

January 22, 2021

Status Verified

January 1, 2021

Enrollment Period

3.8 years

First QC Date

June 3, 2016

Last Update Submit

January 21, 2021

Conditions

Pre-eclampsiaPregnancy

Keywords

pre-eclampsiacitrullinepregnancy

Outcome Measures

Primary Outcomes (1)

  • number of days between the therapeutic initiation and childbirth

    childbirth

Study Arms (2)

L-Citrulline

EXPERIMENTAL

Bolus (9g) after patient stabilization, then 3g 3 times a day until delivery

Drug: Citrulline

Lactose

PLACEBO COMPARATOR

Bolus (9g) after patient stabilization, then 3g 3 times a day until delivery

Drug: Placebo

Interventions

CitrullineDRUG

Citrulline supplementation

L-Citrulline
PlaceboDRUG

Placebo

Lactose

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • age \>= 18 years old
  • pregnant woman
  • singleton pregnancy
  • woman with pre-eclampsia (\<36 weeks) without indication of forthcoming extraction
  • subjects affiliated with an appropriate social security system
  • subjects out of context of guardianship
  • written signed informed consent form

You may not qualify if:

  • age \< 18 years old
  • isolated hypertension or isolated proteinuria
  • severe pre-eclampsia with indication of forthcoming extraction in emergency
  • term pregnancy \>= 36 Weeks when diagnosis is done
  • multiple pregnancy
  • lactose intolerance
  • context of guardianship

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

CHU de Nantes

Nantes, 44093, France

Location

Hôpital Cochin (Maternité Port-Royal)

Paris, 75014, France

Location

Related Publications (1)

  • 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.

    PMID: 39638148DERIVED

MeSH Terms

Conditions

Pre-Eclampsia

Interventions

Citrulline

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-InducedPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, DiaminoAmino AcidsAmino Acids, Peptides, and Proteins

Study Officials

  • Nobert Winer, Dr

    Nantes University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 3, 2016

First Posted

June 16, 2016

Study Start

February 20, 2017

Primary Completion

December 1, 2020

Study Completion

December 1, 2020

Last Updated

January 22, 2021

Record last verified: 2021-01

Locations

FR(2)