Clinical trial NCT02772887: Nutraceutical Citrulline in Pregnancy
Official title: Phase 1 Trial Citrulline and Type 2 Diabetes in Pregnancy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Type 2 Diabetes
Keywords: pregnancy
type 2 diabetes
asymmetric dimethylarginine
L-arginine
L-citrulline
placental growth factor (PlGF)
blood pressure
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2016-05-16
Enrollment: 8
Sex: FEMALE
Minimum age (years): 14
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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 pregnant women with type 2 diabetes will increase the plasma L-arginine/ADMA ratio, lower maternal blood pressure and increase maternal levels of placental growth factor (PlGF).

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, obesity and history of preeclampsia. Specifically, the risk of preeclampsia is five times greater in women with diabetes.

Several lines of evidence indicate that endothelial dysfunction is a central feature of the pathophysiology of preeclampsia. 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 concentrations are higher early in pregnancy among women who later develop preeclampsia. This protocol describes a randomized placebo-controlled trial of L-citrulline in 40 pregnant women with type 2 diabetes from approximately sixteen to nineteen weeks gestation, to determine whether L-citrulline supplementation increases the plasma L-arginine/ADMA ratio, lowers maternal blood pressure and increases a circulating marker of placental function (placental growth factor PLGF).

Eligibility criteria: Inclusion Criteria:

* Singleton pregnancy
* Type 2 diabetes with hemoglobin A1c \<8
* Gestational age at randomization between 14 and 16 weeks based on clinical information
* Maternal age between 14 and 40 years

Exclusion Criteria:

* Chronic hypertension
* Major fetal anomaly
* Fetal 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, known illicit drug or alcohol abuse during current pregnancy
* Already taking L-citrulline as a supplement (1gram/day or more)

Primary outcomes:
measure: Blood pressure
timeFrame: approximately 20 weeks
Secondary outcomes:
measure: Placental growth factor (PlGF)
timeFrame: approximately 20 weeks
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
Study officials:
References: