Cardiovascular DiseasesLQTSNCT00005176
Long QT Syndrome-Population Genetics and Cardiac Studies
An observational study of Cardiovascular Diseases and Heart Diseases, run by University of Rochester at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 100 years
- Conditions the study is for
- Cardiovascular Diseases, Heart Diseases, Ventricular Arrhythmia
- How many people
- 2,125 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 1985to Apr 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: As of the 2013 closeout report, 1329 probands with clinical dx of LQTS and members of their extended families have been enrolled in the LQTS Registry. By ECG classification, this includes 3420 probands and affected family members, 3533 unaffected family members, and 2105 family members with borderline QTc. Of those, 2125 have had mutations identified.
Probands are required to have clinical dx of LQTS. Family members are also invited to participate regardless of their dx.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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 (n=4,000) 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 (n=370 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 1,200 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.
- Medical subject headings
- Cardiovascular Diseases, Heart Diseases, Long QT Syndrome
What is being measured
The primary outcome is the main question the study is designed to answer.
None. This is an observational study.
Measured: By study end
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2000 (estimated)
- Study startAug 1985
- Primary completionApr 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (116)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by University of RochesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 2,125 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Arthur J. Moss, University of Rochester
- Investigators
- Arthur Moss, Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005176
- Sponsor's protocol ID
- 1053
- Other IDs
- R01HL033843-16
- Acronym
- LQTS
- Status last verified
- Oct 2015
- First submitted
- 25 May 2000
- Last updated
- 22 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Weitkamp LR, Moss AJ: The Long QT (Romano-Ward) Syndrome Locus, LQT, is Probably Linked to the HLA Loci. Cytogenet Cell Genet, 40:775, 1985
Locati E, Schwartz PJ, Moss AJ, Crampton RS: Long-Term Survival After Left Cervico-Thoracic Sympathectomy in High Risk Long QT Syndrome Patients With Refractory Ventricular Arrhythmias. J Am Coll Cardiol, 7:234A, 1986
De Ambroggi L, Bertoni T, Locati E, Stramba-Badiale M, Schwartz PJ. Mapping of body surface potentials in patients with the idiopathic long QT syndrome. Circulation. 1986 Dec;74(6):1334-45. doi: 10.1161/01.cir.74.6.1334.
PubMed 3779919Vincent GM. The heart rate of Romano-Ward syndrome patients. Am Heart J. 1986 Jul;112(1):61-4. doi: 10.1016/0002-8703(86)90678-2.
PubMed 3728288Moss AJ. Prolonged QT-interval syndromes. JAMA. 1986 Dec 5;256(21):2985-7. No abstract available.
PubMed 3773216Merri M, Benhorin J, Alberti M, Locati E, Moss AJ. Electrocardiographic quantitation of ventricular repolarization. Circulation. 1989 Nov;80(5):1301-8. doi: 10.1161/01.cir.80.5.1301.
PubMed 2805266Benhorin J, Merri M, Alberti M, Locati E, Moss AJ, Hall WJ, Cui L. Long QT syndrome. New electrocardiographic characteristics. Circulation. 1990 Aug;82(2):521-7. doi: 10.1161/01.cir.82.2.521.
PubMed 2271025Moss AJ. Clinical management of patients with the long QT syndrome: drugs, devices, and gene-specific therapy. Pacing Clin Electrophysiol. 1997 Aug;20(8 Pt 2):2058-60. doi: 10.1111/j.1540-8159.1997.tb03627.x.
PubMed 9272508Zareba W, Moss AJ, le Cessie S, Locati EH, Robinson JL, Hall WJ, Andrews ML. Risk of cardiac events in family members of patients with long QT syndrome. J Am Coll Cardiol. 1995 Dec;26(7):1685-91. doi: 10.1016/0735-1097(95)60383-2.
PubMed 7594104Weitkamp LR, Moss AJ, Lewis RA, Hall WJ, MacCluer JW, Schwartz PJ, Locati EH, Tzivoni D, Vincent GM, Robinson JL, et al. Analysis of HLA and disease susceptibility: chromosome 6 genes and sex influence long-QT phenotype. Am J Hum Genet. 1994 Dec;55(6):1230-41.
PubMed 7977384Malfatto G, Beria G, Sala S, Bonazzi O, Schwartz PJ. Quantitative analysis of T wave abnormalities and their prognostic implications in the idiopathic long QT syndrome. J Am Coll Cardiol. 1994 Feb;23(2):296-301. doi: 10.1016/0735-1097(94)90410-3.
PubMed 7905012Zareba W, Moss AJ, le Cessie S, Hall WJ. T wave alternans in idiopathic long QT syndrome. J Am Coll Cardiol. 1994 Jun;23(7):1541-6. doi: 10.1016/0735-1097(94)90653-x.
PubMed 8195511Schwartz PJ, Priori SG, Locati EH, Napolitano C, Cantu F, Towbin JA, Keating MT, Hammoude H, Brown AM, Chen LS, Colatsky TJ. Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate. Implications for gene-specific therapy. Circulation. 1995 Dec 15;92(12):3381-6. doi: 10.1161/01.cir.92.12.3381.
PubMed 8521555De Ferrari GM, Nador F, Beria G, Sala S, Lotto A, Schwartz PJ. Effect of calcium channel block on the wall motion abnormality of the idiopathic long QT syndrome. Circulation. 1994 May;89(5):2126-32. doi: 10.1161/01.cir.89.5.2126.
PubMed 8181137Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995 Mar 10;80(5):805-11. doi: 10.1016/0092-8674(95)90359-3.
PubMed 7889574
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long QT Syndrome-Population Genetics and Cardiac Studies
- ClinicalTrials.gov ID
- NCT00005176
- Acronym / sponsor ID
- LQTS / 1053
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,125 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Aug 1985
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 26 May 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (n=4,000) 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 (n=370 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 1,200 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 design
- Observational model
- Family based
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- As of the 2013 closeout report, 1329 probands with clinical dx of LQTS and members of their extended families have been enrolled in the LQTS Registry. By ECG classification, this includes 3420 probands and affected family members, 3533 unaffected family members, and 2105 family members with borderline QTc. Of those, 2125 have had mutations identified.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
None. This is an observational study.
Time frame: By study end
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2015.
- BackgroundWeitkamp LR, Moss AJ: The Long QT (Romano-Ward) Syndrome Locus, LQT, is Probably Linked to the HLA Loci. Cytogenet Cell Genet, 40:775, 1985
- BackgroundLocati E, Schwartz PJ, Moss AJ, Crampton RS: Long-Term Survival After Left Cervico-Thoracic Sympathectomy in High Risk Long QT Syndrome Patients With Refractory Ventricular Arrhythmias. J Am Coll Cardiol, 7:234A, 1986
- Background: PubMed 3779919De Ambroggi L, Bertoni T, Locati E, Stramba-Badiale M, Schwartz PJ. Mapping of body surface potentials in patients with the idiopathic long QT syndrome. Circulation. 1986 Dec;74(6):1334-45. doi: 10.1161/01.cir.74.6.1334.
- Background: PubMed 3728288Vincent GM. The heart rate of Romano-Ward syndrome patients. Am Heart J. 1986 Jul;112(1):61-4. doi: 10.1016/0002-8703(86)90678-2.
- Background: PubMed 3773216Moss AJ. Prolonged QT-interval syndromes. JAMA. 1986 Dec 5;256(21):2985-7. No abstract available.
- Background: PubMed 2805266Merri M, Benhorin J, Alberti M, Locati E, Moss AJ. Electrocardiographic quantitation of ventricular repolarization. Circulation. 1989 Nov;80(5):1301-8. doi: 10.1161/01.cir.80.5.1301.
- Background: PubMed 2271025Benhorin J, Merri M, Alberti M, Locati E, Moss AJ, Hall WJ, Cui L. Long QT syndrome. New electrocardiographic characteristics. Circulation. 1990 Aug;82(2):521-7. doi: 10.1161/01.cir.82.2.521.
- Background: PubMed 9272508Moss AJ. Clinical management of patients with the long QT syndrome: drugs, devices, and gene-specific therapy. Pacing Clin Electrophysiol. 1997 Aug;20(8 Pt 2):2058-60. doi: 10.1111/j.1540-8159.1997.tb03627.x.
- Background: PubMed 7594104Zareba W, Moss AJ, le Cessie S, Locati EH, Robinson JL, Hall WJ, Andrews ML. Risk of cardiac events in family members of patients with long QT syndrome. J Am Coll Cardiol. 1995 Dec;26(7):1685-91. doi: 10.1016/0735-1097(95)60383-2.
- Background: PubMed 7977384Weitkamp LR, Moss AJ, Lewis RA, Hall WJ, MacCluer JW, Schwartz PJ, Locati EH, Tzivoni D, Vincent GM, Robinson JL, et al. Analysis of HLA and disease susceptibility: chromosome 6 genes and sex influence long-QT phenotype. Am J Hum Genet. 1994 Dec;55(6):1230-41.
- Background: PubMed 7905012Malfatto G, Beria G, Sala S, Bonazzi O, Schwartz PJ. Quantitative analysis of T wave abnormalities and their prognostic implications in the idiopathic long QT syndrome. J Am Coll Cardiol. 1994 Feb;23(2):296-301. doi: 10.1016/0735-1097(94)90410-3.
- Background: PubMed 8195511Zareba W, Moss AJ, le Cessie S, Hall WJ. T wave alternans in idiopathic long QT syndrome. J Am Coll Cardiol. 1994 Jun;23(7):1541-6. doi: 10.1016/0735-1097(94)90653-x.
Related trials for Cardiovascular Diseases
Active, not recruitingPhase 3
ENDOTHELION Study Group: Effect of Bosentan in NAION Patients
Ischemic Optic Neuropathy
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arthur Moss principal investigator
University of Rochester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Diseases and Heart Diseases, run by University of Rochester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
None. This is an observational study. (time frame: By study end). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005176, which also lists 116 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2015.