Ignite Creation Date:
2024-05-05 @ 11:07 AM
Last Modification Date:
2024-10-26 @ 9:04 AM
Study NCT ID:
NCT00005176
Status:
COMPLETED
Last Update Posted:
2015-10-22
First Post:
2000-05-25
Brief Title:
Long QT Syndrome-Population Genetics and Cardiac Studies
Sponsor:
University of Rochester
Organization:
University of Rochester
Study Overview
Official Title:
Long QT Syndrome-Population Genetics and Cardiac Studies
Status:
COMPLETED
Status Verified Date:
2015-10
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:
LQTS
Brief Summary:
To investigate the clinical genetic and cardiologic aspects of the Long QT Syndrome a predominantly hereditary disease with episodic malignant arrhythmias and sudden death and a demonstrated gene linkage in a large pedigree
Detailed Description:
BACKGROUND
The Long QT Syndrome LQTS is an infrequently occurring disorder of unknown cause in which affected individuals have an unusual electrocardiographic repolarization abnormality and a propensity to syncope and fatal ventricular tachyarrhythmias The first family with LQTS was described by Jervell and Lange-Nielsen in 1957 Three sudden deaths occurred in four deaf children with QT prolongation two other children and the parents were healthy with normal hearing and normal electrocardiograms The findings were interpreted as a pattern of autosomal recessive inheritance Subsequent reports identified LQTS families with normal hearing Romano-Ward Syndrome having a pattern of occurrence suggesting autosomal dominant inheritance
DESIGN NARRATIVE
Beginning in 1985 patients and their unaffected relatives were longitudinally followed in this multicenter study to develop and validate widely applicable clinical criteria for stratifying the risk of life-threatening arrhythmias A population of genetically deaf students was surveyed to identify additional families with the unique association of Long QT Syndrome and congenital deafness in order to expand the data base for genetic studies in the recessive form of the disorder the Jervell and Lange-Nielsen Syndrome Pedigrees of selected Long QT Syndrome families were recorded to better understand the inheritance of the dominant form of the disorder the Romano-Ward Syndrome Genetic studies were conducted using human leukocyte antigen and other protein markers in order to investigate the gene locus for the autosomal dominant form of the syndrome A select group of 30 patients and 30 unaffected relatives had 24-hour Holter monitoring treadmill exercise Valsalva maneuver and handgrip stress tests to determine if the patients had a unique cardiovascular response to autonomic dysfunction
The study was renewed in 1993 The renewal had six aims The first examined genetic heterogeneity in LQTS by testing for Harvey-ras-1 gene linkage in the existing well-characterized LQTS families with evidence of a major gene by segregation analysis in LQTS families that did not show Harvey-ras- 1 linkage a search for other closely linked genetic markers was initiated The second aim explored by segregation analysis the likelihood that a second gene coexisted with the Harvey-ras-1 gene to explain a more malignant disease process in some LQTS families than in others The third established normal standards for six quantitative repolarization parameters on a healthy population n4000 using digitized ECG recordings and biomedical and statistical techniques with adjustment for age gender race and heart rate The fourth aim continued the existing LQTS registry with ongoing enrollment of new families and follow-up of new and existing LQTS pedigrees n370 families in order to provide a central repository for this disorder especially as it related to the natural history of this disorder and ongoing genetic analyses The fifth aim investigated the static 12-lead ECG and dynamic 24-hour Holter ECG aspects of ventricular repolarization in LQTS families showing Harvey-ras gene linkage to upgrade the ECG categorization of delayed repolarization using the Harvey-ras- 1 marker as the gold standard to identify affected and unaffected individuals The sixth aim continued the prospective longitudinal follow-up study of LQTS families to better understand the long-term clinical course of this disorder time-dependent survivorship analyses were performed to evaluate the effects of various clinical features repolarization severity QTc length Harvey-ras-I gene linkage and therapeutic efficacy with antiadrenergic therapy if data permits on outcome event rates syncope and sudden death in the LQTS probands
The study has been renewed several times to expand the pedigrees of LQTS families and family members enrolled in the registry identify new LQTS gene mutations and expand the number of gene-identified affected and unaffected members in LQTS families with known gene mutations investigate phenotype-genotype relationships in 200 genotyped families involving 1200 affected and unaffected family members regarding the clinical course of LQTS T-wave repolarization triggering factors for cardiac events and co-morbidity associations all by genotype The study remains a multicenter project with six clinical centers a genetic component involving four molecular genetic labs a statistical genetic component a biostatistical component and a coordinating center
The Long QT Syndrome LQTS is an infrequently occurring disorder of unknown cause in which affected individuals have an unusual electrocardiographic repolarization abnormality and a propensity to syncope and fatal ventricular tachyarrhythmias The first family with LQTS was described by Jervell and Lange-Nielsen in 1957 Three sudden deaths occurred in four deaf children with QT prolongation two other children and the parents were healthy with normal hearing and normal electrocardiograms The findings were interpreted as a pattern of autosomal recessive inheritance Subsequent reports identified LQTS families with normal hearing Romano-Ward Syndrome having a pattern of occurrence suggesting autosomal dominant inheritance
DESIGN NARRATIVE
Beginning in 1985 patients and their unaffected relatives were longitudinally followed in this multicenter study to develop and validate widely applicable clinical criteria for stratifying the risk of life-threatening arrhythmias A population of genetically deaf students was surveyed to identify additional families with the unique association of Long QT Syndrome and congenital deafness in order to expand the data base for genetic studies in the recessive form of the disorder the Jervell and Lange-Nielsen Syndrome Pedigrees of selected Long QT Syndrome families were recorded to better understand the inheritance of the dominant form of the disorder the Romano-Ward Syndrome Genetic studies were conducted using human leukocyte antigen and other protein markers in order to investigate the gene locus for the autosomal dominant form of the syndrome A select group of 30 patients and 30 unaffected relatives had 24-hour Holter monitoring treadmill exercise Valsalva maneuver and handgrip stress tests to determine if the patients had a unique cardiovascular response to autonomic dysfunction
The study was renewed in 1993 The renewal had six aims The first examined genetic heterogeneity in LQTS by testing for Harvey-ras-1 gene linkage in the existing well-characterized LQTS families with evidence of a major gene by segregation analysis in LQTS families that did not show Harvey-ras- 1 linkage a search for other closely linked genetic markers was initiated The second aim explored by segregation analysis the likelihood that a second gene coexisted with the Harvey-ras-1 gene to explain a more malignant disease process in some LQTS families than in others The third established normal standards for six quantitative repolarization parameters on a healthy population n4000 using digitized ECG recordings and biomedical and statistical techniques with adjustment for age gender race and heart rate The fourth aim continued the existing LQTS registry with ongoing enrollment of new families and follow-up of new and existing LQTS pedigrees n370 families in order to provide a central repository for this disorder especially as it related to the natural history of this disorder and ongoing genetic analyses The fifth aim investigated the static 12-lead ECG and dynamic 24-hour Holter ECG aspects of ventricular repolarization in LQTS families showing Harvey-ras gene linkage to upgrade the ECG categorization of delayed repolarization using the Harvey-ras- 1 marker as the gold standard to identify affected and unaffected individuals The sixth aim continued the prospective longitudinal follow-up study of LQTS families to better understand the long-term clinical course of this disorder time-dependent survivorship analyses were performed to evaluate the effects of various clinical features repolarization severity QTc length Harvey-ras-I gene linkage and therapeutic efficacy with antiadrenergic therapy if data permits on outcome event rates syncope and sudden death in the LQTS probands
The study has been renewed several times to expand the pedigrees of LQTS families and family members enrolled in the registry identify new LQTS gene mutations and expand the number of gene-identified affected and unaffected members in LQTS families with known gene mutations investigate phenotype-genotype relationships in 200 genotyped families involving 1200 affected and unaffected family members regarding the clinical course of LQTS T-wave repolarization triggering factors for cardiac events and co-morbidity associations all by genotype The study remains a multicenter project with six clinical centers a genetic component involving four molecular genetic labs a statistical genetic component a biostatistical component and a coordinating center
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL033843-16 | NIH | None | httpsreporternihgovquickSearchR01HL033843-16 |