Angiotensinogen Variants and Adverse Pregnancy Outcomes

This study has been completed.
Sponsor:
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00005400
First received: May 25, 2000
Last updated: June 23, 2005
Last verified: May 2005
  Purpose

To examine angiotensinogen genetic variants and adverse pregnancy outcomes.


Condition
Cardiovascular Diseases
Heart Diseases
Pre-Eclampsia

Study Type: Observational
Study Design: Observational Model: Natural History

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Study Start Date: August 1995
Estimated Study Completion Date: July 2003
Detailed Description:

BACKGROUND:

Early in gestation maternal blood volume normally expands by an unknown mechanism; failure of this normal adaptation to pregnancy has been associated with common adverse pregnancy outcomes including preeclampsia, intrauterine growth retardation, and premature labor. The renin-angiotensin system has a critical role in controlling maternal fluid volume and probably in the pathophysiology of these serious complications of pregnancy. Kenneth Ward and his group have recently discovered DNA variants which cause amino acid substitutions in angiotensinogen (renin substrate), one of which (T235) is strongly associated with preeclampsia. They hypothesize that functionally different angiotensinogen proteins may underlie the pathophysiology of preeclampsia and other related disorders (such as intrauterine growth retardation and premature labor) by not allowing normal volume expansion to occur.

The four interrelated approaches in the study should lead to a better understanding of the role of angiotensinogen in pregnancy and of the pathophysiology of preeclampsia. Unlike any previous finding in preeclamptic patients, the genetic alteration in angiotensinogen described is an intrinsic defect which, although it may be modified by other factors, cannot be 'secondary' to other pathophysiologic variables. This molecular hypothesis demands a reinterpretation of many prior findings in preeclampsia, fetal growth retardation, and premature labor based on angiotensinogen genotypes. The DNA and plasma collected for this study will be invaluable resources for future molecular investigations of abnormal pregnancies.

DESIGN NARRATIVE:

Four different strategies were used. First, a prospective, epidemiologic survey of 24,000 pregnancies was conducted to determine the role of the T235 variant in common disorders of pregnancy. From this population, nulligravida volunteers, 150 who were homozygous for T235 variant and 150 who were homozygous for the alternative M235 allele, were selected for a longitudinal study of maternal-fetal physiology and biochemistry in order to determine how and when the T235 variant exerted its adverse effect. Taking advantage of the large average family size in Utah, the female relatives of women with preeclampsia were also studied in order to define the genetics of important angiotensinogen variants. Finally, DNA from preeclamptic patients was examined for additional mutations in the angiotensinogen gene which may offer unique pathophysiologic insight.

The study was renewed in 1999 for another four years to investigate the hypothesis that disease-associated angiotensinogen alleles promote abnormal spiral artery remodeling and inhibit maternal plasma volume expansion.

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

No eligibility criteria

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00005400

Sponsors and Collaborators
Investigators
Investigator: Kenneth Ward University of Utah
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00005400     History of Changes
Other Study ID Numbers: 4317
Study First Received: May 25, 2000
Last Updated: June 23, 2005
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Cardiovascular Diseases
Heart Diseases
Pre-Eclampsia
Hypertension, Pregnancy-Induced
Pregnancy Complications

ClinicalTrials.gov processed this record on September 30, 2014