Oral L-Citrulline and ADMA in Pregnancy

NCT ID: NCT00743210

Last Updated: 2014-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2013-06-30

Brief Summary

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.

Detailed Description

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.

Conditions

Blood Pressure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

1

Oral L-citrulline, 3 grams once per day for 3 weeks.

Group Type: EXPERIMENTAL

L-citrulline

Intervention Type: DRUG

Oral L-citrulline, 3 grams once per day for 3 weeks.

2

Placebo, 3 grams once per day for 3 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo, 3 grams once per day for 3 weeks.

Interventions

L-citrulline

Oral L-citrulline, 3 grams once per day for 3 weeks.

Intervention Type: DRUG

Placebo

Placebo, 3 grams once per day for 3 weeks.

Intervention Type: DRUG

Eligibility 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)

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Robert Powers

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carl A Hubel, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Obstetrics & Gynecology and Reproductive Sciences, University of Pittsburgh

Locations

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

P01HD030367-09

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2P01HD030367-ARG

Identifier Type: -

Identifier Source: org_study_id