Ignite Creation Date:
2024-05-05 @ 11:07 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005357
Status:
COMPLETED
Last Update Posted:
2016-02-10
First Post:
2000-05-25
Brief Title:
Pulmonary Hypertension--Mechanisms and Family Registry
Sponsor:
Vanderbilt University
Organization:
Vanderbilt University
Study Overview
Official Title:
Pulmonary Hypertension--Mechanisms and Family Registry
Status:
COMPLETED
Status Verified Date:
2016-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To establish a registry of primary pulmonary hypertension PPH a lethal disease which causes progressive obstruction of small pulmonary arteries and to investigate basic mechanisms of the disease
Detailed Description:
BACKGROUND
Primary pulmonary hypertension PPH is a serious disease of unknown cause in which small arteries in the lungs become obstructed Mean survival is less than three years and women develop PPH twice as commonly as men It is familial FPPH in about 6 percent of cases The National FPPH Registry was established in 1994 to collect and analyze family history and clinical data from PPH families to better characterize the disease phenotype as well as to identify the underlying genetic etiology Through the collection of 72 families FPPH has been shown to be inherited as an autosomal dominant disorder with incomplete penetrance and genetic anticipation Micro-satellite marker studies in six families have identified linkage to chromosome 2q31 without evidence of genetic heterogeneity
DESIGN NARRATIVE
The study established a national registry of familial PPH FPPH The primary goal of the family registry was to establish and expand the database of FPPH pedigrees to definitively establish the mode of inheritance of FPPH which initial segregation analysis suggested was autosomal dominant The FPPH family registry provided the framework for the linkage analysis of the molecular search for basic mechanisms of PPH The investigators developed a tissue bank for specimens DNA and transformed lymphocytes from families and patients with pulmonary hypertension both for their investigations and as a national resource for other interested investigators Their search used three different approaches to investigate for a FPPH gene locus First they performed karyotyping and high resolution chromosome studies to search for a chromosomal translocation interstitial deletion or inversion the finding of which would implicate a specific gene locus Second they pursued the proposed association of human leukocyte antigen HLA tissue type with familial PPH in a parallel attempt to identify a related locus about which to perform an intensified molecular search using regional mapping studies of closely linked markers Finally they performed linkage analysis in selected PPH families which had the most informative inheritance patterns using polymerase chain reaction PCR based microsatellite markers for selected candidate genes including those for transforming growth factor beta endothelin beta globin and HLA An additional promising approach included a search for linkage of FPPH to genes with GC-rich trinucleotide repeats as had been successful for other diseases with genetic anticipation including Fragile X syndrome myotonic dystrophy and Huntingtons disease
The study was renewed in 1999 through 2003 to expand the registry in order to obtain enough PPH families to localize and clone the PPH gene and support the DNA bank for these and further studies Other goals included prospective and biochemical mediator studies of obligate gene carriers who did not have clinically evident PPH This aim determined which mediators first became abnormal during developing PPH and defined the natural history of pre-symptomatic diseases In addition the registry broadened its scope to include sporadic PPH patients including those who had used appetite suppressant medications who were screened for gene mutations
Primary pulmonary hypertension PPH is a serious disease of unknown cause in which small arteries in the lungs become obstructed Mean survival is less than three years and women develop PPH twice as commonly as men It is familial FPPH in about 6 percent of cases The National FPPH Registry was established in 1994 to collect and analyze family history and clinical data from PPH families to better characterize the disease phenotype as well as to identify the underlying genetic etiology Through the collection of 72 families FPPH has been shown to be inherited as an autosomal dominant disorder with incomplete penetrance and genetic anticipation Micro-satellite marker studies in six families have identified linkage to chromosome 2q31 without evidence of genetic heterogeneity
DESIGN NARRATIVE
The study established a national registry of familial PPH FPPH The primary goal of the family registry was to establish and expand the database of FPPH pedigrees to definitively establish the mode of inheritance of FPPH which initial segregation analysis suggested was autosomal dominant The FPPH family registry provided the framework for the linkage analysis of the molecular search for basic mechanisms of PPH The investigators developed a tissue bank for specimens DNA and transformed lymphocytes from families and patients with pulmonary hypertension both for their investigations and as a national resource for other interested investigators Their search used three different approaches to investigate for a FPPH gene locus First they performed karyotyping and high resolution chromosome studies to search for a chromosomal translocation interstitial deletion or inversion the finding of which would implicate a specific gene locus Second they pursued the proposed association of human leukocyte antigen HLA tissue type with familial PPH in a parallel attempt to identify a related locus about which to perform an intensified molecular search using regional mapping studies of closely linked markers Finally they performed linkage analysis in selected PPH families which had the most informative inheritance patterns using polymerase chain reaction PCR based microsatellite markers for selected candidate genes including those for transforming growth factor beta endothelin beta globin and HLA An additional promising approach included a search for linkage of FPPH to genes with GC-rich trinucleotide repeats as had been successful for other diseases with genetic anticipation including Fragile X syndrome myotonic dystrophy and Huntingtons disease
The study was renewed in 1999 through 2003 to expand the registry in order to obtain enough PPH families to localize and clone the PPH gene and support the DNA bank for these and further studies Other goals included prospective and biochemical mediator studies of obligate gene carriers who did not have clinically evident PPH This aim determined which mediators first became abnormal during developing PPH and defined the natural history of pre-symptomatic diseases In addition the registry broadened its scope to include sporadic PPH patients including those who had used appetite suppressant medications who were screened for gene mutations
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL048164 | NIH | None | httpsreporternihgovquickSearchR01HL048164 |