Role of L-citrulline in Prevention of Pregnancy Associated Hypertension

Role of L-citrulline in Prevention of Pregnancy Associated Hypertension in Nulliparous Women

The target population for our study is healthy nulliparous pregnant women (first pregnancy) between the 12-16 week of pregnancy.

If a subject is eligible, written consent will be obtained by person to person contact. Eligible participants will be randomized to receive either daily L-citrulline supplementation or placebo.

Study Overview

• Status: Suspended
• Conditions: Gestational Hypertension; Pregnancy Induced Hypertension; Preeclampsia and Eclampsia
• Intervention / Treatment: Drug: Placebo; Drug: L-citrulline

Detailed Description

Healthy nulliparous pregnant women (first pregnancy) between the 12-16 week of pregnancy will be eligible for this study. The purpose of this study will be to determine if daily supplementation of oral L-citrulline can reduce the incidence of pregnancy induced hypertension. This will be a double blind study, subjects will be randomized to receive either L-citrulline (3 gram sachet) or a placebo for a total of 8 weeks. Participants will be asked to provide urine and blood samples at time of enrollment, be asked to respond to a phone survey to assess for side effects, and again be asked to provide urine and blood samples at the end of 8 weeks. Participants will continue with routine prenatal care throughout the study.

• Study Type: Interventional
• Enrollment (Estimated): 338
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Alan J Lee, MD; Phone Number: 409-772-1571; Email: aljlee@utmb.edu
• Study Contact Backup: Name: Sangeeta Jain, MD; Phone Number: 409-772-1571; Email: sajain@utmb.edu

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77555-0156
      • University of Texas Medical Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Nulliparous (no previous pregnancy greater than 20 weeks)
• Gestational age of pregnancy between 12 and 16 weeks

Exclusion Criteria:

• Known fetal anomaly or chromosomal abnormality
• Early fetal growth restriction
• Fetal demise or planned termination
• Participation in another study that may influence this study
• Known maternal kidney disease
• Known maternal electrolyte imbalance
• Known allergies to study interventions
• Preexisting hypertension (chronic hypertension)
• Known gastric ulcer
• Incarcerated status
• Planned delivery at non-UTMB hospital
• Known lactose intolerance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo; Oral placebo, 3 grams milk powder sachet, taken once daily	Drug: Placebo; Milk powder placebo
Experimental: Daily L-citrulline; L-citrulline, 3 grams L-citrulline sachet, taken once daily	Drug: L-citrulline; 3 gram sachet, L-citrulline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of pregnancy induced hypertension	Incidence of pregnancy induced hypertension conditions (gestational hypertension, preeclampsia, or eclampsia) between treatment and placebo groups will be assessed by chart review after end of pregnancy	To be assessed by chart review at time of delivery which generally will occur 8-9 months after randomization.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in bioavailability of L-citrulline and asymmetric dimethyl arginine (ADMA) with oral L-citrulline administration	Assessment of change in serum L-citrulline and asymmetric dimethyl arginine (ADMA ) levels with L-citrulline administration between treatment and placebo groups. Serum samples will be collected at the beginning of study and after 8 weeks and assayed for ADMA and L-citrulline	Baseline at start of study and again after 8 weeks treatment
Change in maternal nitric oxide levels with L-citrulline supplementation	Assessment of change in nitric oxide levels between treatment and placebo groups by measurement of baseline and 8 week post treatment urine nitrate and nitrite concentrations	Baseline at start of study and again after 8 weeks treatment
Maternal blood pressure	Assessment of maternal blood pressure throughout study	Baseline at start of study, and approximately every 1-4 weeks after randomization at prenatal appointments throughout pregnancy. Also at time of delivery approximately 8-9 months after randomization..
Maternal Morbidity	Composite assessment of incidence of maternal outcomes to include development of preeclampsia; Hemolysis, Elevated liver enzymes, Low Platelets (HELLP) syndrome; eclampsia; indicated preterm birth less than 32 weeks due to hypertension related disorders	To be assessed by chart review at time of delivery which generally will occur 8-9 months after randomization.
Birth weight	To assess the actual birthweight of neonate by chart review at time of delivery. This outcome is different than fetal growth restriction noted in outcome 5.	To be assessed by chart review at time of delivery which generally will occur 8-9 months after randomization.
Neonatal Outcomes	To determine the incidence of neonatal outcomes by chart review after delivery that include respiratory distress syndrome, necrotising enterocolitis, bronchopulmonary dysplasia (BPD), and BPD related pulmonary hypertension, retinopathy of prematurity, age at full feed, and length of hospital stay, fetal growth restriction defined as less than 10% of predicted gestational age, fetal death after 20 weeks gestation, and neonatal death	To be assessed by chart review 8-9 months after enrollment at time of delivery

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2021
• Primary Completion (Estimated): July 30, 2024
• Study Completion (Estimated): July 30, 2024

Study Registration Dates

• First Submitted: June 16, 2021
• First Submitted That Met QC Criteria: July 16, 2021
• First Posted (Actual): July 28, 2021

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Pregnancy Induced Hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Eclampsia; Pre-Eclampsia; Hypertension, Pregnancy-Induced
• Other Study ID Numbers: 20-0167

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No