Oral L-Citrulline and ADMA in Pregnancy

Blood Pressure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00743210
• Other study ID #: 2P01HD030367-ARG
• Secondary ID: P01HD030367-09
• Status: Completed
• Phase: Phase 1
• First received: August 26, 2008
• Last updated: July 14, 2014
• Start date: January 2010
• Est. completion date: June 2013

Study information

• Verified date: July 2014
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 14 Years to 40 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Blood Pressure

Intervention

Drug:
• L-citrulline
Oral L-citrulline, 3 grams once per day for 3 weeks.
• Placebo
Placebo, 3 grams once per day for 3 weeks.

Locations

Country	Name	City	State
United States	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pittsburgh	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		3 weeks	No
Secondary	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.		3 weeks	No