Oral L-Citrulline and ADMA in Pregnancy

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Robert Powers, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00743210
First received: August 26, 2008
Last updated: July 14, 2014
Last verified: July 2014
  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.


Condition Intervention Phase
Blood Pressure
Drug: L-citrulline
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Phase 1 Study of Oral L-citrulline on ADMA/L-arginine and Endothelial-dependent Vascular Function in Pregnancy.

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: January 2010
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Oral L-citrulline, 3 grams once per day for 3 weeks.
Drug: L-citrulline
Oral L-citrulline, 3 grams once per day for 3 weeks.
Placebo Comparator: 2
Placebo, 3 grams once per day for 3 weeks.
Drug: Placebo
Placebo, 3 grams once per day for 3 weeks.

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.

  Eligibility

Ages Eligible for Study:   14 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00743210

Locations
United States, Pennsylvania
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Carl A Hubel, PhD Department of Obstetrics & Gynecology and Reproductive Sciences, University of Pittsburgh
  More Information

No publications provided

Responsible Party: Robert Powers, Associate Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00743210     History of Changes
Other Study ID Numbers: 2P01HD030367-ARG, P01HD030367-09
Study First Received: August 26, 2008
Last Updated: July 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
pregnancy
obesity
asymmetric dimethylarginine
L-arginine
L-citrulline

ClinicalTrials.gov processed this record on October 19, 2014