Nutraceutical Citrulline in Pregnancy

Study Overview
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Brief Summary
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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
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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).

Official Title
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Phase 1 Trial Citrulline and Type 2 Diabetes in Pregnancy

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Dietary Supplement: L-Citrulline
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Citrulline<br>Oral L-citrulline, 3 grams once per day for 3 weeks. | Dietary Supplement: L-Citrulline<br>* amino acid supplement<br>|
| Placebo Comparator: Placebo<br>Placebo, 3 grams once per day for 3 weeks. | Other: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | research measure | approximately 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Placental growth factor (PlGF) | quantified by ELISA | approximately 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pregnancy, type 2 diabetes, asymmetric dimethylarginine, L-arginine, L-citrulline, placental growth factor (PlGF), blood pressure