Nutraceutical Citrulline in Pregnancy

Not Applicable

Terminated

• Conditions: Type 2 Diabetes
• Interventions: Dietary Supplement: L-Citrulline; Other: Placebo

• Registration Number: NCT02772887
• Lead Sponsor: University of Pittsburgh

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).

Study Timeline

• Study First Submitted: 2016-02-12
• Study First Submitted QC: 2016-05-11
• Study First Posted: 2016-05-16
• Study Start: 2016-08
• Status Verified: 2019-05
• Primary Completion: 2019-05
• Study Completion: 2019-05
• Last Update Submitted: 2019-05-28
• Last Update Posted: 2019-05-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 8

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Citrulline	L-Citrulline	Oral L-citrulline, 3 grams once per day for 3 weeks.
Placebo	Placebo	Placebo, 3 grams once per day for 3 weeks.

Primary Outcome Measures

Name	Time	Method
Blood pressure	approximately 20 weeks	research measure

Secondary Outcome Measures

Name	Time	Method
Placental growth factor (PlGF)	approximately 20 weeks	quantified by ELISA

Trial Locations

Locations (1)

Magee-Womens Hospital of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States