L-Arginine and Antioxidant Vitamins During Pregnancy to Reduce Preeclampsia (L-Arg)

Supplementation With L-Arginine and Antioxidant Vitamins During Pregnancy in a Medical Food to Reduce the Risk of Preeclampsia in a High Risk Population

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.

Study Overview

• Status: Terminated
• Conditions: Pre-Eclampsia
• Intervention / Treatment: Procedure: L-arginine supplementation in a medical food; Procedure: Vitamin C and E supplementation in a medical food

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.

• Study Type: Interventional
• Enrollment (Actual): 585
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • D.f.
    • Mexico City, D.f., Mexico, 11000
      • Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-6142
      • Univesity of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 32 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Development of preeclampsia	During pregnancy

Secondary Outcome Measures

Outcome Measure	Time Frame
Development of eclampsia	During pregnancy
Occurrence of HELP syndrome	During pregnancy
Occurrence of preterm labor, preterm premature rupture of the membranes	During pregnancy
Gestational age at delivery	End of pregnancy

Collaborators and Investigators

• Sponsor: Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes
• Collaborators: University of Pennsylvania; Bill and Melinda Gates Foundation
• Investigators: Principal Investigator: Felipe Vadillo-Ortega, M.D.,Ph.D., Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2001
• Study Completion (Actual): November 1, 2006

Study Registration Dates

• First Submitted: May 4, 2007
• First Submitted That Met QC Criteria: May 4, 2007
• First Posted (Estimate): May 7, 2007

Study Record Updates

• Last Update Posted (Estimate): May 8, 2007
• Last Update Submitted That Met QC Criteria: May 7, 2007
• Last Verified: April 1, 2007

More Information

Terms related to this study

• Keywords: Pre-Eclampsia; Preterm labor; Hypertension,pregnancy-induced
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Eclampsia; Pre-Eclampsia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: 212250-02071