Oral L-Citrulline and ADMA in Pregnancy
Condition: Blood Pressure
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): L-citrulline; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Oral L-citrulline, 3 grams once per day for 3 weeks.; Placebo, 3 grams once per day for 3 weeks.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: pregnancy; obesity; asymmetric dimethylarginine; L-arginine; L-citrulline