Expired Study
This study is not currently recruiting Study Participants on ClinicalConnection.com. If you would like to find active studies please search for clinical trials.

Pittsburgh, Pennsylvania 15213


Purpose:

The purpose of this study is to determine if oral of L-citrulline (3 grams/day) for 3 weeks provided in mid-pregnancy to obese subjects will decrease the plasma ADMA/L-arginine ratio, lower maternal blood pressure, improve endothelial-dependent vascular function and peripheral vascular stiffness, and improve uterine artery Doppler resistance and flow.


Study summary:

The pregnancy-specific syndrome preeclampsia is a leading cause of maternal and fetal morbidity and mortality. The underlying cause of preeclampsia is unknown, however several pre-existing maternal conditions are associated with an increased risk of preeclampsia including: diabetes, hypertension, renal dysfunction, and obesity. Among these conditions, obesity has been increasing in the population, such that 30% of the adult population in the US is now considered obese, and because of this obesity has the largest attributable risk for preeclampsia, accounting for 15 to 32% of the population attributable risk for preeclampsia. There is abundant evidence that pre-pregnancy obesity increases the risk of preeclampsia. However, it is unknown how pre-pregnancy obesity increases the risk of preeclampsia, how obesity-mediated metabolic aberrations interact with current hypotheses of the pathogenesis of preeclampsia, and why only a subset of obese women (~6-8%) develops preeclampsia. Several lines of evidence indicate that endothelial dysfunction is a central feature of the pathophysiology of preeclampsia, and endothelial dysfunction is a common endpoint of obesity. Asymmetric dimethylarginine (ADMA) is a methylated metabolite of the amino acid L-arginine and an endogenous inhibitor of nitric oxide synthase (NOS). High concentrations of ADMA contribute to endothelial dysfunction and ADMA inhibits angiogenesis and arteriogenesis, activities important in pregnancy and deficient in preeclampsia. ADMA is higher in obesity and ADMA concentrations are higher early in pregnancy among women who later develop preeclampsia. This protocol describes a randomized placebo-controlled trial of L-citrulline vs. placebo in 80 obese pregnant women from twelve to twenty weeks gestation, to determine whether L-citrulline supplementation decreases the plasma ADMA/L-arginine ratio, lowers maternal blood pressure, improves endothelial-dependent vascular function and peripheral vascular stiffness, and improvement in uterine artery Doppler resistance and flow. We will compare the data obtained from these obese pregnant women to the same measures obtained from 40 untreated lean pregnant women.


Criteria:

Inclusion Criteria: - Pre-pregnancy body mass index greater than or equal to 30kg/m2 - Primiparity - Singleton pregnancy - Gestational age at randomization between 10 and 14 weeks based on clinical information and evaluation of earliest ultrasound - Maternal age between 14 and 40 years Exclusion Criteria: - chronic hypertension - pregestational diabetes on medication (insulin, glyburide) - major fetal anomaly or demise - planned termination of the pregnancy - collagen vascular disease (autoimmune disease) on medication - renal disease - epilepsy or other seizure disorder - active or chronic liver disease - heart disease - cigarette smoker - known illicit drug or alcohol abuse during current pregnancy - already taking L-citrulline as a supplement (1gram/day or more)


Study is Available At:


Original ID:

2P01HD030367-ARG


NCT ID:

NCT00743210


Secondary ID:

P01HD030367-09


Study Acronym:


Brief Title:

Oral L-Citrulline and ADMA in Pregnancy


Official Title:

Phase 1 Study of Oral L-citrulline on ADMA/L-arginine and Endothelial-dependent Vascular Function in Pregnancy.


Overall Status:

Completed


Study Phase:

Phase 1


Genders:

Female


Minimum Age:

14 Years


Maximum Age:

40 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of Pittsburgh


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Randomized, Endpoint Classification: E


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

41


Enrollment Type:

Actual


Overall Contact Information

Official Name:Carl A Hubel, PhD
Principal Investigator
Department of Obstetrics & Gynecology and Reproductive Sciences, University of Pittsburgh

Study Dates

Start Date:January 2010
Completion Date:June 2013
Completion Type:Actual
Primary Completion Date:June 2013
Primary Completion Type:Actual
Verification Date:July 2014
Last Changed Date:July 14, 2014
First Received Date:August 26, 2008

Study Outcomes

Outcome Type:Secondary Outcome
Measure:To evaluate the changes in plasma ADMA/L-arginine ratio, endothelial-dependent vascular function and peripheral vascular stiffness, and uterine artery Doppler resistance and flow.
Time Frame:3 weeks
Safety Issues:False
Outcome Type:Primary Outcome
Measure:To evaluate blood pressure changes in response to oral L-citrulline or placebo treatment in uncomplicated obese pregnant women during the second trimester of pregnancy.
Time Frame:3 weeks
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:L-citrulline
Description:Oral L-citrulline, 3 grams once per day for 3 weeks.
Arm Name:1
Intervention Type:Drug
Name:Placebo
Description:Placebo, 3 grams once per day for 3 weeks.
Arm Name:2

Study Arms

Study Arm Type:Placebo Comparator
Arm Name:2
Description:Placebo, 3 grams once per day for 3 weeks.
Study Arm Type:Experimental
Arm Name:1
Description:Oral L-citrulline, 3 grams once per day for 3 weeks.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:University of Pittsburgh
Agency Class:NIH
Agency Type:Collaborator
Agency Name:Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


This study is not currently recruiting Study Participants. The form below is not enabled.