Genetic and Environmental Characteristics of Primary Pulmonary Hypertension

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ClinicalTrials.gov Identifier: NCT00091546

Recruitment Status : Completed

First Posted : September 13, 2004

Last Update Posted : February 2, 2016

Sponsor:

Collaborator:

National Heart, Lung, and Blood Institute (NHLBI)

Information provided by (Responsible Party):

Jim Loyd, Vanderbilt University

Study Description

Brief Summary:

The goal of this study is to identify the modifying genes and environmental features that regulate the clinical expression of mutations in bone morphogenetic protein receptor 2 (BMPR2); to develop the understanding of how BMPR2 mutations result in disease; and to identify the undiscovered genetic mutations that cause primary pulmonary hypertension (PPH).

Condition or disease
Lung Diseases Hypertension, Pulmonary

Detailed Description:

BACKGROUND:

PPH is a progressive disease that causes obstruction of the smallest arteries in the lungs, which often leads to heart failure. It threatens the lives of thousands of individuals. PPH affects both genders at any age, although females are affected twice as often as males. In a recent important advance, mutations in BMPR2 were associated with both familial and sporadic PPH. Because only 20% of people with a BMPR2 mutation ever develop PPH, other genes or modifying biologic events must contribute to the clinical development of the disease. PPH was recently renamed Idiopathic Pulmonary Arterial Hypertension or Familial Pulmonary Arterial Hypertension.

DESIGN NARRATIVE:

This study will utilize a database and specimen bank developed from 100 families affected by PPH across the United States. In families with genetic mutations not yet identified, changes in the BMPR2 gene will be studied, including in the promoter and intronic regions, and chance recombination events that could confirm another locus near 2q33 will be examined. New methods will look for modifier genes in large families with known mutations; examine kindreds for mitochondrial DNA haplotypes; and test candidate genes, including NOS-1, NOS-3, and the serotonin transporter. This study will determine the functional mechanisms by which variations found in the BMPR2 alleles alter BMP signal transduction by defining the biochemical effects of the mutant proteins on signaling pathways. In addition, the study will examine the perceived risks and benefits of clinical genetic testing and counseling in individuals from families at high risk for PPH and will determine how this new information might be most helpful to these individuals and their families.

Study Design


Study Type :	Observational
Actual Enrollment :	3000 participants
Observational Model:	Cohort
Time Perspective:	Retrospective
Official Title:	Genetic and Environmental Pathogenesis of PPH
Study Start Date :	August 2003
Actual Primary Completion Date :	July 2009
Actual Study Completion Date :	July 2009

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Pulmonary arterial hypertension

MedlinePlus related topics: Pulmonary Hypertension

Genetic and Rare Diseases Information Center resources: Pulmonary Arterial Hypertension

U.S. FDA Resources

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

New development of pulmonary arterial hypertension (penetrance), age of onset, and survival [ Time Frame: Measured through genetic analysis ]

Biospecimen Retention: Samples With DNA

Specimens from 100 families affected by PPH

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	up to 100 Years (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Database and specimen bank developed from 100 families affected by PPH

Criteria

Inclusion Criteria:

Diagnosis of PPH, or family members of individuals diagnosed with PPH, for inclusion in the database and specimen bank

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00091546

Locations


United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-2650

Sponsors and Collaborators

Vanderbilt University

National Heart, Lung, and Blood Institute (NHLBI)

Investigators


Study Chair:	James Loyd	Vanderbilt University Medical Center

More Information

Publications of Results:

Cogan JD, Pauciulo MW, Batchman AP, Prince MA, Robbins IM, Hedges LK, Stanton KC, Wheeler LA, Phillips JA 3rd, Loyd JE, Nichols WC. High frequency of BMPR2 exonic deletions/duplications in familial pulmonary arterial hypertension. Am J Respir Crit Care Med. 2006 Sep 1;174(5):590-8. Epub 2006 May 25.

Other Publications:

Cogan JD, Vnencak-Jones CL, Phillips JA 3rd, Lane KB, Wheeler LA, Robbins IM, Garrison G, Hedges LK, Loyd JE. Gross BMPR2 gene rearrangements constitute a new cause for primary pulmonary hypertension. Genet Med. 2005 Mar;7(3):169-74.

Meyrick BO, Friedman DB, Billheimer DD, Cogan JD, Prince MA, Phillips JA 3rd, Loyd JE. Proteomics of transformed lymphocytes from a family with familial pulmonary arterial hypertension. Am J Respir Crit Care Med. 2008 Jan 1;177(1):99-107. Epub 2007 Oct 11.

Phillips JA 3rd, Poling JS, Phillips CA, Stanton KC, Austin ED, Cogan JD, Wheeler L, Yu C, Newman JH, Dietz HC, Loyd JE. Synergistic heterozygosity for TGFbeta1 SNPs and BMPR2 mutations modulates the age at diagnosis and penetrance of familial pulmonary arterial hypertension. Genet Med. 2008 May;10(5):359-65. doi: 10.1097/GIM.0b013e318172dcdf.

Newman JH, Phillips JA 3rd, Loyd JE. Narrative review: the enigma of pulmonary arterial hypertension: new insights from genetic studies. Ann Intern Med. 2008 Feb 19;148(4):278-83. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Johnson JA, Vnencak-Jones CL, Cogan JD, Loyd JE, West J. Copy-number variation in BMPR2 is not associated with the pathogenesis of pulmonary arterial hypertension. BMC Med Genet. 2009 Jun 16;10:58. doi: 10.1186/1471-2350-10-58.


Responsible Party:	Jim Loyd, Professor, Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00091546 History of Changes
Other Study ID Numbers:	166 P01HL072058 ( U.S. NIH Grant/Contract )
First Posted:	September 13, 2004 Key Record Dates
Last Update Posted:	February 2, 2016
Last Verified:	February 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes

Additional relevant MeSH terms:


Hypertension Lung Diseases Hypertension, Pulmonary Familial Primary Pulmonary Hypertension	Vascular Diseases Cardiovascular Diseases Respiratory Tract Diseases

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