Heart DiseasesNCT00024505
Multidisciplinary Study of Right Ventricular Dysplasia
An observational study of Heart Diseases and Arrhythmogenic Right Ventricular Dysplasia, run by University of Arizona at 1 site in United States.
Trial summary
The purpose of this study is to investigate the cardiac, clinical, and genetic aspects of arrhythmogenic right ventricular dysplasia (ARVD), a progressive disorder that predominantly affects the right side of the heart and causes ventricular arrhythmias. Read more about this study
- Who is it for?
- Ages 12 to 90 years
- Conditions the study is for
- Heart Diseases, Arrhythmogenic Right Ventricular Dysplasia
- How many people
- 320 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2001to Jul 2010
- 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 12 to 90 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Referals to enrolling centers from communities
Who may be able to join
- Males and females over the age of puberty
- Suspected ARVD based on the presence of major or minor Task Force Criteria
Who cannot join
- Children younger than 12 years of age
- Internal cardioverter defibrillator (ICD) in place for more than 2 years (for probands)
- Individuals with monomorphic ventricular ectopy of predominantly RBBB morphology
- Individuals with obvious cardiomyopathic abnormalities of structure or function predominantly affecting the left ventricle
- Individuals with other conditions that might be mistaken for right ventricular dysplasia such as congenital heart disease, e.g., atrial septal defect, anomalous drainage of the pulmonary vessels into the right atrium, and Ebstein's malformation
- Individuals unwilling to undergo diagnostic testing at the nearest enrolling center
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to investigate the cardiac, clinical, and genetic aspects of arrhythmogenic right ventricular dysplasia (ARVD), a progressive disorder that predominantly affects the right side of the heart and causes ventricular arrhythmias.
Read the detailed description
BACKGROUND:
ARVD is an uncommon disorder but is considered a major cause of sudden death and life-threatening arrhythmia, in particular in the young population. The prevalence of ARVD is unknown but is certainly underestimated because of the difficulties in obtaining a correct diagnosis. It appears to be particularly frequent in certain geographical areas, probably for a founder effect, such as in northeast Italy, where a large number of ARVD cases and families have been described. A noncontrolled study of the University of Padua reported a frequency of familial forms of about 30 percent, indicating the existence of a defective gene in a large proportion of cases. In the United States the frequency of the disease is unknown, but the number of cases seems to be increasing.
The etiology of ARVD was unknown until very recently. The main hypothesis involved apoptotic mechanisms and, in some cases, a viral infection. However, in the last couple of years, two genes causing ARVD have been identified. The first one encodes plakoglobin, a protein of the cardiac junctions with adhesive and signaling functions. The second ARVD gene is the cardiac ryanodine receptor (RYR2), which has been characterized only very recently by Dr. Danieli's group. In fact, this discovery is so recent that in this study, RYR2 is still considered a potential candidate. The discovery of the first disease genes provides the basis for a candidate gene approach following the hypothesis of a "final common pathway." Thus, major candidates become genes involved in cell-cell adhesion and encoding ion channels.
DESIGN NARRATIVE:
This is a multidisciplinary, multicenter, collaborative study investigating the cardiac, clinical, and genetic aspects of ARVD. The specific aims are (1) to establish a North American ARVD Registry enrolling ARVD patients and their family members, based on standardized diagnostic test criteria, in a prospective longitudinal follow-up study; (2) to determine the genetic background of ARVD by identifying chromosomal loci and specific gene mutations associated with this disorder; (3) to determine the influence of the genotype on the clinical course of patients with ARVD and explore phenotype-genotype associations that will contribute to improved diagnosis, risk stratification, and therapy; and (4) to develop quantitative methods to assess right ventricular function in order to enhance the specificity and sensitivity of ARVD diagnosis.
- Medical subject headings
- Heart Diseases, Arrhythmogenic Right Ventricular Dysplasia
What is being measured
The primary outcome is the main question the study is designed to answer.
Identifying the cardiac, clinical, and genetic aspects of ARVD
Measured: Measured during the course of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2001 (estimated)
- Study startSep 2001
- Primary completionJul 2010
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (53)Papers the sponsor has linked to this study.
- Other trials for Heart DiseasesStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 320 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Frank Marcus, University of Arizona
- Investigators
- Frank I. Marcus, MD, Principal investigator, University of ArizonaJeffrey Towbin, Principal investigator, Baylor College of MedicineWojciech Zareba, Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00024505
- Sponsor's protocol ID
- 983
- Other IDs
- U01HL065594-05, U01HL065594, U01HL065652, U01HL065691
- Status last verified
- Jan 2013
- First submitted
- 18 Sep 2001
- Last updated
- 17 Jan 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Marcus F, Towbin JA, Zareba W, Moss A, Calkins H, Brown M, Gear K; ARVD/C Investigators. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C): a multidisciplinary study: design and protocol. Circulation. 2003 Jun 17;107(23):2975-8. doi: 10.1161/01.CIR.0000071380.43086.29. No abstract available.
PubMed 12814984Yoerger DM, Marcus F, Sherrill D, Calkins H, Towbin JA, Zareba W, Picard MH; Multidisciplinary Study of Right Ventricular Dysplasia Investigators. Echocardiographic findings in patients meeting task force criteria for arrhythmogenic right ventricular dysplasia: new insights from the multidisciplinary study of right ventricular dysplasia. J Am Coll Cardiol. 2005 Mar 15;45(6):860-5. doi: 10.1016/j.jacc.2004.10.070.
PubMed 15766820Scheinman MM, Crawford MH. Echocardiographic findings and the search for a gold standard in patients with arrhythmogenic right ventricular dysplasia. J Am Coll Cardiol. 2005 Mar 15;45(6):866-7. doi: 10.1016/j.jacc.2004.12.021. No abstract available.
PubMed 15766821Indik JH, Dallas WJ, Ovitt T, Wichter T, Gear K, Marcus FI. Do patients with right ventricular outflow tract ventricular arrhythmias have a normal right ventricular wall motion? A quantitative analysis compared to normal subjects. Cardiology. 2005;104(1):10-5. doi: 10.1159/000086047. Epub 2005 May 28.
PubMed 15942177Dalal D, Nasir K, Bomma C, Prakasa K, Tandri H, Piccini J, Roguin A, Tichnell C, James C, Russell SD, Judge DP, Abraham T, Spevak PJ, Bluemke DA, Calkins H. Arrhythmogenic right ventricular dysplasia: a United States experience. Circulation. 2005 Dec 20;112(25):3823-32. doi: 10.1161/CIRCULATIONAHA.105.542266. Epub 2005 Dec 12.
PubMed 16344387Bowles NE, Ni J, Marcus F, Towbin JA. The detection of cardiotropic viruses in the myocardium of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol. 2002 Mar 6;39(5):892-5. doi: 10.1016/s0735-1097(02)01688-1.
PubMed 11869858Rampazzo A, Nava A, Malacrida S, Beffagna G, Bauce B, Rossi V, Zimbello R, Simionati B, Basso C, Thiene G, Towbin JA, Danieli GA. Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2002 Nov;71(5):1200-6. doi: 10.1086/344208. Epub 2002 Oct 8.
PubMed 12373648Rampazzo A, Beffagna G, Nava A, Occhi G, Bauce B, Noiato M, Basso C, Frigo G, Thiene G, Towbin J, Danieli GA. Arrhythmogenic right ventricular cardiomyopathy type 1 (ARVD1): confirmation of locus assignment and mutation screening of four candidate genes. Eur J Hum Genet. 2003 Jan;11(1):69-76. doi: 10.1038/sj.ejhg.5200914.
PubMed 12529708Gear K, Marcus F. Arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation. 2003 Feb 4;107(4):e31-3. doi: 10.1161/01.cir.0000053943.38763.70. No abstract available.
PubMed 12569915Nasir K, Tandri H, Rutberg J, Tichnell C, Spevak P, Crossan J, Baughman KL, Kasper EK, Tomaselli GF, Berger R, Calkins H. Filtered QRS duration on signal-averaged electrocardiography predicts inducibility of ventricular tachycardia in arrhythmogenic right ventricle dysplasia. Pacing Clin Electrophysiol. 2003 Oct;26(10):1955-60. doi: 10.1046/j.1460-9592.2003.00302.x.
PubMed 14516335Tandri H, Friedrich MG, Calkins H, Bluemke DA. MRI of arrhythmogenic right ventricular cardiomyopathy/dysplasia. J Cardiovasc Magn Reson. 2004;6(2):557-63. doi: 10.1081/jcmr-120030583.
PubMed 15137340Tandri H, Bomma C, Calkins H, Bluemke DA. Magnetic resonance and computed tomography imaging of arrhythmogenic right ventricular dysplasia. J Magn Reson Imaging. 2004 Jun;19(6):848-58. doi: 10.1002/jmri.20078.
PubMed 15170788Castillo E, Tandri H, Rodriguez ER, Nasir K, Rutberg J, Calkins H, Lima JA, Bluemke DA. Arrhythmogenic right ventricular dysplasia: ex vivo and in vivo fat detection with black-blood MR imaging. Radiology. 2004 Jul;232(1):38-48. doi: 10.1148/radiol.2321030688.
PubMed 15220492Tandri H, Bluemke DA, Ferrari VA, Bomma C, Nasir K, Rutberg J, Tichnell C, James C, Lima JA, Calkins H. Findings on magnetic resonance imaging of idiopathic right ventricular outflow tachycardia. Am J Cardiol. 2004 Dec 1;94(11):1441-5. doi: 10.1016/j.amjcard.2004.07.150.
PubMed 15566923Roguin A, Bomma CS, Nasir K, Tandri H, Tichnell C, James C, Rutberg J, Crosson J, Spevak PJ, Berger RD, Halperin HR, Calkins H. Implantable cardioverter-defibrillators in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol. 2004 May 19;43(10):1843-52. doi: 10.1016/j.jacc.2004.01.030.
PubMed 15145110
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multidisciplinary Study of Right Ventricular Dysplasia
- ClinicalTrials.gov ID
- NCT00024505
- Acronym / sponsor ID
- 983
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 320 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Sep 2001
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 18 Sep 2001 (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.
The purpose of this study is to investigate the cardiac, clinical, and genetic aspects of arrhythmogenic right ventricular dysplasia (ARVD), a progressive disorder that predominantly affects the right side of the heart and causes ventricular arrhythmias.
Detailed description
BACKGROUND:
ARVD is an uncommon disorder but is considered a major cause of sudden death and life-threatening arrhythmia, in particular in the young population. The prevalence of ARVD is unknown but is certainly underestimated because of the difficulties in obtaining a correct diagnosis. It appears to be particularly frequent in certain geographical areas, probably for a founder effect, such as in northeast Italy, where a large number of ARVD cases and families have been described. A noncontrolled study of the University of Padua reported a frequency of familial forms of about 30 percent, indicating the existence of a defective gene in a large proportion of cases. In the United States the frequency of the disease is unknown, but the number of cases seems to be increasing.
The etiology of ARVD was unknown until very recently. The main hypothesis involved apoptotic mechanisms and, in some cases, a viral infection. However, in the last couple of years, two genes causing ARVD have been identified. The first one encodes plakoglobin, a protein of the cardiac junctions with adhesive and signaling functions. The second ARVD gene is the cardiac ryanodine receptor (RYR2), which has been characterized only very recently by Dr. Danieli's group. In fact, this discovery is so recent that in this study, RYR2 is still considered a potential candidate. The discovery of the first disease genes provides the basis for a candidate gene approach following the hypothesis of a "final common pathway." Thus, major candidates become genes involved in cell-cell adhesion and encoding ion channels.
DESIGN NARRATIVE:
This is a multidisciplinary, multicenter, collaborative study investigating the cardiac, clinical, and genetic aspects of ARVD. The specific aims are (1) to establish a North American ARVD Registry enrolling ARVD patients and their family members, based on standardized diagnostic test criteria, in a prospective longitudinal follow-up study; (2) to determine the genetic background of ARVD by identifying chromosomal loci and specific gene mutations associated with this disorder; (3) to determine the influence of the genotype on the clinical course of patients with ARVD and explore phenotype-genotype associations that will contribute to improved diagnosis, risk stratification, and therapy; and (4) to develop quantitative methods to assess right ventricular function in order to enhance the specificity and sensitivity of ARVD diagnosis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 12 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Referals to enrolling centers from communities
Key inclusion criteria (2 listed)
- Males and females over the age of puberty
- Suspected ARVD based on the presence of major or minor Task Force Criteria
Key exclusion criteria (6 listed)
- Children younger than 12 years of age
- Internal cardioverter defibrillator (ICD) in place for more than 2 years (for probands)
- Individuals with monomorphic ventricular ectopy of predominantly RBBB morphology
- Individuals with obvious cardiomyopathic abnormalities of structure or function predominantly affecting the left ventricle
- Individuals with other conditions that might be mistaken for right ventricular dysplasia such as congenital heart disease, e.g., atrial septal defect, anomalous drainage of the pulmonary vessels into the right atrium, and Ebstein's malformation
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
Identifying the cardiac, clinical, and genetic aspects of ARVD
Time frame: Measured during the course of the study
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 17 Jan 2013.
- Background: PubMed 12814984Marcus F, Towbin JA, Zareba W, Moss A, Calkins H, Brown M, Gear K; ARVD/C Investigators. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C): a multidisciplinary study: design and protocol. Circulation. 2003 Jun 17;107(23):2975-8. doi: 10.1161/01.CIR.0000071380.43086.29. No abstract available.
- Background: PubMed 15766820Yoerger DM, Marcus F, Sherrill D, Calkins H, Towbin JA, Zareba W, Picard MH; Multidisciplinary Study of Right Ventricular Dysplasia Investigators. Echocardiographic findings in patients meeting task force criteria for arrhythmogenic right ventricular dysplasia: new insights from the multidisciplinary study of right ventricular dysplasia. J Am Coll Cardiol. 2005 Mar 15;45(6):860-5. doi: 10.1016/j.jacc.2004.10.070.
- Background: PubMed 15766821Scheinman MM, Crawford MH. Echocardiographic findings and the search for a gold standard in patients with arrhythmogenic right ventricular dysplasia. J Am Coll Cardiol. 2005 Mar 15;45(6):866-7. doi: 10.1016/j.jacc.2004.12.021. No abstract available.
- Background: PubMed 15942177Indik JH, Dallas WJ, Ovitt T, Wichter T, Gear K, Marcus FI. Do patients with right ventricular outflow tract ventricular arrhythmias have a normal right ventricular wall motion? A quantitative analysis compared to normal subjects. Cardiology. 2005;104(1):10-5. doi: 10.1159/000086047. Epub 2005 May 28.
- Background: PubMed 16344387Dalal D, Nasir K, Bomma C, Prakasa K, Tandri H, Piccini J, Roguin A, Tichnell C, James C, Russell SD, Judge DP, Abraham T, Spevak PJ, Bluemke DA, Calkins H. Arrhythmogenic right ventricular dysplasia: a United States experience. Circulation. 2005 Dec 20;112(25):3823-32. doi: 10.1161/CIRCULATIONAHA.105.542266. Epub 2005 Dec 12.
- Background: PubMed 11869858Bowles NE, Ni J, Marcus F, Towbin JA. The detection of cardiotropic viruses in the myocardium of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol. 2002 Mar 6;39(5):892-5. doi: 10.1016/s0735-1097(02)01688-1.
- Background: PubMed 12373648Rampazzo A, Nava A, Malacrida S, Beffagna G, Bauce B, Rossi V, Zimbello R, Simionati B, Basso C, Thiene G, Towbin JA, Danieli GA. Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2002 Nov;71(5):1200-6. doi: 10.1086/344208. Epub 2002 Oct 8.
- Background: PubMed 12529708Rampazzo A, Beffagna G, Nava A, Occhi G, Bauce B, Noiato M, Basso C, Frigo G, Thiene G, Towbin J, Danieli GA. Arrhythmogenic right ventricular cardiomyopathy type 1 (ARVD1): confirmation of locus assignment and mutation screening of four candidate genes. Eur J Hum Genet. 2003 Jan;11(1):69-76. doi: 10.1038/sj.ejhg.5200914.
- Background: PubMed 12569915Gear K, Marcus F. Arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation. 2003 Feb 4;107(4):e31-3. doi: 10.1161/01.cir.0000053943.38763.70. No abstract available.
- Background: PubMed 14516335Nasir K, Tandri H, Rutberg J, Tichnell C, Spevak P, Crossan J, Baughman KL, Kasper EK, Tomaselli GF, Berger R, Calkins H. Filtered QRS duration on signal-averaged electrocardiography predicts inducibility of ventricular tachycardia in arrhythmogenic right ventricle dysplasia. Pacing Clin Electrophysiol. 2003 Oct;26(10):1955-60. doi: 10.1046/j.1460-9592.2003.00302.x.
- Background: PubMed 15137340Tandri H, Friedrich MG, Calkins H, Bluemke DA. MRI of arrhythmogenic right ventricular cardiomyopathy/dysplasia. J Cardiovasc Magn Reson. 2004;6(2):557-63. doi: 10.1081/jcmr-120030583.
- Background: PubMed 15170788Tandri H, Bomma C, Calkins H, Bluemke DA. Magnetic resonance and computed tomography imaging of arrhythmogenic right ventricular dysplasia. J Magn Reson Imaging. 2004 Jun;19(6):848-58. doi: 10.1002/jmri.20078.
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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.
Frank I. Marcus, MD principal investigator
University of Arizona
Jeffrey Towbin principal investigator
Baylor College of Medicine
Wojciech Zareba 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 Heart Diseases and Arrhythmogenic Right Ventricular Dysplasia, run by University of Arizona 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?
The sponsor lists 2 inclusion and 6 exclusion criteria. 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 17 Jan 2013. 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?
Identifying the cardiac, clinical, and genetic aspects of ARVD (time frame: Measured during the course of the study). 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 NCT00024505, which also lists 53 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 17 Jan 2013.