Role of L-citrulline in Prevention of Pregnancy Associated Hypertension
Primary Purpose
Pregnancy Induced Hypertension, Preeclampsia and Eclampsia, Gestational Hypertension
Status
Suspended
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
L-citrulline
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Pregnancy Induced Hypertension focused on measuring Pregnancy Induced Hypertension
Eligibility Criteria
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
Sites / Locations
- University of Texas Medical Branch
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Placebo
Daily L-citrulline
Arm Description
Oral placebo, 3 grams milk powder sachet, taken once daily
L-citrulline, 3 grams L-citrulline sachet, taken once daily
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
Maternal blood pressure
Assessment of maternal blood pressure throughout study
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
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.
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
Full Information
NCT ID
NCT04979793
First Posted
June 16, 2021
Last Updated
August 14, 2023
Sponsor
The University of Texas Medical Branch, Galveston
1. Study Identification
Unique Protocol Identification Number
NCT04979793
Brief Title
Role of L-citrulline in Prevention of Pregnancy Associated Hypertension
Official Title
Role of L-citrulline in Prevention of Pregnancy Associated Hypertension in Nulliparous Women
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Suspended
Why Stopped
At the request of the PI
Study Start Date
July 28, 2021 (Actual)
Primary Completion Date
July 30, 2024 (Anticipated)
Study Completion Date
July 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Medical Branch, Galveston
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pregnancy Induced Hypertension, Preeclampsia and Eclampsia, Gestational Hypertension
Keywords
Pregnancy Induced Hypertension
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
338 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Active Comparator
Arm Description
Oral placebo, 3 grams milk powder sachet, taken once daily
Arm Title
Daily L-citrulline
Arm Type
Experimental
Arm Description
L-citrulline, 3 grams L-citrulline sachet, taken once daily
Intervention Type
Drug
Intervention Name(s)
L-citrulline
Intervention Description
3 gram sachet, L-citrulline
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Milk powder placebo
Primary Outcome Measure Information:
Title
Incidence of pregnancy induced hypertension
Description
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
Time Frame
To be assessed by chart review at time of delivery which generally will occur 8-9 months after randomization.
Secondary Outcome Measure Information:
Title
Change in bioavailability of L-citrulline and asymmetric dimethyl arginine (ADMA) with oral L-citrulline administration
Description
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
Time Frame
Baseline at start of study and again after 8 weeks treatment
Title
Change in maternal nitric oxide levels with L-citrulline supplementation
Description
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
Time Frame
Baseline at start of study and again after 8 weeks treatment
Title
Maternal blood pressure
Description
Assessment of maternal blood pressure throughout study
Time Frame
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..
Title
Maternal Morbidity
Description
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
Time Frame
To be assessed by chart review at time of delivery which generally will occur 8-9 months after randomization.
Title
Birth weight
Description
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.
Time Frame
To be assessed by chart review at time of delivery which generally will occur 8-9 months after randomization.
Title
Neonatal Outcomes
Description
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
Time Frame
To be assessed by chart review 8-9 months after enrollment at time of delivery
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Facility Information:
Facility Name
University of Texas Medical Branch
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555-0156
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Role of L-citrulline in Prevention of Pregnancy Associated Hypertension
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