Clinical trial NCT00469846: L-Arginine and Antioxidant Vitamins During Pregnancy to Reduce Preeclampsia
Official title: Supplementation With L-Arginine and Antioxidant Vitamins During Pregnancy in a Medical Food to Reduce the Risk of Preeclampsia in a High Risk Population
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pre-Eclampsia
Keywords: Pre-Eclampsia
Hypertension,pregnancy-induced
Preterm labor
Lead sponsor: Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes
Sponsor class: OTHER_GOV
Collaborators: name: University of Pennsylvania
name: Bill and Melinda Gates Foundation
First posted: 2007-05-07
Enrollment: 585
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 32
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is intended to assess the efficacy of L-arginine supplementation with antioxidant vitamins delivered in a medical food in reducing the incidence of preeclampsia in a high-risk population.

Detailed description: Preeclampsia is a syndrome of unknown origin characterized by hypertension, edema and proteinuria. It usually appears in the third trimester and occurs most frequently in primigravidas. Preeclampsia may be complicated by life-threatening conditions including seizures, severe hepatic dysfunction, renal failure and coagulopathy; it is one of the leading causes of maternal morbidity and mortality worldwide. Preeclampsia is cited as the leading cause of maternal death in surveys of maternal mortality in Mexico (25% of maternal deaths).

Specific Aim 1. To assess the efficacy of L-arginine supplementation with antioxidant vitamins delivered in a medical food in reducing the incidence of preeclampsia in a high-risk population. Two other groups will receive the food (bars) either with antioxidant vitamins alone or without vitamins in order to test the impact of vitamin supplements on prevention of preeclampsia. The primary hypothesis to be tested is that supplemental L-arginine in combination with antioxidant vitamins will significantly reduce preeclampsia (hypertension and proteinuria) and its complications in a high-risk population (women whose blood pressure is \> 140/90 after 20 weeks gestation without proteinuria). Secondary hypotheses to be tested include that antioxidant vitamin supplementation contributes to the reduction in preeclampsia; that supplemental L-arginine and antioxidant vitamins will improve neonatal outcomes (reduced incidence of prematurity and intrauterine growth retardation); that preeclampsia is correlated inversely with plasma L-arginine levels, directly with the plasma levels of the endogenous NO synthase inhibitor, asymmetric dimethyl arginine (ADMA), and inversely with urinary NO metabolites, a marker of endogenous NO production; and that preeclampsia is inversely correlated with maternal plasma levels of antioxidant vitamins.

Eligibility criteria: Inclusion Criteria:

* Previous pregnancy complicated with pre-eclampsia/eclampsia
* Singleton pregnancy
* Gestational age \>20 weeks \<34 weeks
* Protein excretion \< 300 mg/day

Exclusion Criteria:

* Multiple gestation
* Major fetal anomaly
* Pre-existing hypertension
* Pre-existing renal disease
* Diabetes
* Collagen vascular disease
* Cancer or strong family history of cancer in first degree relatives
* Preexisting maternal disease requiring medication

Primary outcomes:
measure: Development of preeclampsia
timeFrame: During pregnancy
Secondary outcomes:
measure: Development of eclampsia
timeFrame: During pregnancy
measure: Occurrence of HELP syndrome
timeFrame: During pregnancy
measure: Occurrence of preterm labor, preterm premature rupture of the membranes
timeFrame: During pregnancy
measure: Gestational age at delivery
timeFrame: End of pregnancy
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Univesity of Pennsylvania
state: Pennsylvania
city: Mexico City
country: Mexico
facility: Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes
state: D.f.
Study officials:
affiliation: Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes
name: Felipe Vadillo-Ortega, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vadillo-Ortega F, Perichart-Perera O, Espino S, Avila-Vergara MA, Ibarra I, Ahued R, Godines M, Parry S, Macones G, Strauss JF. Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial. BMJ. 2011 May 19;342:d2901. doi: 10.1136/bmj.d2901.