Cardiovascular DiseasesNCT00005526
Genetic Basis of Abdominal Aortic Aneurysm
An observational study of Cardiovascular Diseases and Heart Diseases, run by National Heart, Lung, and Blood Institute (NHLBI).
Trial summary
To identify the genetic (major genes) and environmental factors responsible for the significant aggregation of abdominal aortic aneurysm (AAA) among relatives of affected individuals. Read more about this study
- Who is it for?
- Ages Up to 100 years, men only
- Conditions the study is for
- Cardiovascular Diseases, Heart Diseases, Aortic Aneurysm, Abdominal
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Aug 1991to Nov 2001
- 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
- Men only
- No healthy volunteers
- Child, Adult, Older adult
No eligibility criteria
About this study
To identify the genetic (major genes) and environmental factors responsible for the significant aggregation of abdominal aortic aneurysm (AAA) among relatives of affected individuals.
Read the detailed description
BACKGROUND:
Abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta which can, if undetected, lead to rupture. The mortality associated with ruptured AAA is estimated to be 90 percent, while elective repair has a mortality risk of approximately 6 percent. Ruptured AAA is a leading cause of death among older Americans. The identification of markers of AAA risk could lead to preventive intervention. AAA aggregates in families, and segregation analysis shows that familial risk of AAA is best explained by the segregation of a major gene with an autosomal recessive mode of inheritance.
DESIGN NARRATIVE:
Affected relative pairs (primarily sibling pairs) with AAA and no evidence of a family history of a connective tissue disorder were genotyped for 150 highly informative microsatellite polymorphisms marking the autosomal genome at a resolution of 20 cM. The linkage between AAA and these loci was tested using robust affected pedigree member methods to identify genomic regions which might contain genes that predisposed individuals to develop AAA. The existence of predisposing gene(s) were confirmed and their location refined using a defined search strategy, genotyping at increasing levels of resolution, and re-analysis of family data. The predisposing gene(s) were identified by a combination of saturation mapping and molecular analysis of candidate loci. The association of AAA with environmental measures was investigated to determine an equation for estimating risk for relatives of AAA patients based upon environmental measures and genotype. Power calculations based upon the number and structure of families already collected demonstrated the feasibility of identifying genes that predisposed to AAA using this strategy, even in the presence of significant heterogeneity with respect to the loci involved. In addition to identifying genes that were necessary for AAA by linkage analysis, a series of analyses of association were undertaken to identify true susceptibility genes that were neither necessary nor sufficient to cause disease, but which modified an individual's risk of developing AAA.
The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.
- Medical subject headings
- Cardiovascular Diseases, Heart Diseases, Aortic Aneurysm, Abdominal
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 1991
- Study completionNov 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)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 National Heart, Lung, and Blood Institute (NHLBI)The 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
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Robert Ferrell, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005526
- Sponsor's protocol ID
- 5058
- Other IDs
- R01HL044682
- Status last verified
- Aug 2004
- First submitted
- 25 May 2000
- Last updated
- 13 May 2016
- Results posted
- No
Publications
Peters DG, Kassam A, St Jean PL, Yonas H, Ferrell RE. Functional polymorphism in the matrix metalloproteinase-9 promoter as a potential risk factor for intracranial aneurysm. Stroke. 1999 Dec;30(12):2612-6. doi: 10.1161/01.str.30.12.2612.
PubMed 10582986Peters DG, Kassam AB, Yonas H, O'Hare EH, Ferrell RE, Brufsky AM. Comprehensive transcript analysis in small quantities of mRNA by SAGE-lite. Nucleic Acids Res. 1999 Dec 15;27(24):e39. doi: 10.1093/nar/27.24.e39.
PubMed 10572191Vorp DA, Peters DG, Webster MW. Gene expression is altered in perfused arterial segments exposed to cyclic flexure ex vivo. Ann Biomed Eng. 1999 May-Jun;27(3):366-71. doi: 10.1114/1.158.
PubMed 10374728St Jean P, Hart B, Webster M, Steed D, Adamson J, Powell J, Ferrell R. Alpha-1-antitrypsin deficiency in aneurysmal disease. Hum Hered. 1996 Mar-Apr;46(2):92-7. doi: 10.1159/000154333.
PubMed 8666418St Jean PL, Zhang XC, Hart BK, Lamlum H, Webster MW, Steed DL, Henney AM, Ferrell RE. Characterization of a dinucleotide repeat in the 92 kDa type IV collagenase gene (CLG4B), localization of CLG4B to chromosome 20 and the role of CLG4B in aortic aneurysmal disease. Ann Hum Genet. 1995 Jan;59(1):17-24. doi: 10.1111/j.1469-1809.1995.tb01602.x.
PubMed 7762981St Jean PL, Zhang XC, Hart BK, Ferrell RE. Dinucleotide repeat polymorphism at the HPR locus. Hum Mol Genet. 1994 Nov;3(11):2081. No abstract available.
PubMed 7874138Foster K, Ferrell R, King-Underwood L, Povey S, Attwood J, Rennick R, Humphries SE, Henney AM. Description of a dinucleotide repeat polymorphism in the human elastin gene and its use to confirm assignment of the gene to chromosome 7. Ann Hum Genet. 1993 May;57(2):87-96. doi: 10.1111/j.1469-1809.1993.tb00890.x.
PubMed 8368807Peters DG, Kassam AB, Feingold E, Heidrich-O'Hare E, Yonas H, Ferrell RE, Brufsky A. Molecular anatomy of an intracranial aneurysm: coordinated expression of genes involved in wound healing and tissue remodeling. Stroke. 2001 Apr;32(4):1036-42. doi: 10.1161/01.str.32.4.1036.
PubMed 11283408Peters DG, Zhang XC, Benos PV, Heidrich-O'Hare E, Ferrell RE. Genomic analysis of immediate/early response to shear stress in human coronary artery endothelial cells. Physiol Genomics. 2002 Dec 26;12(1):25-33. doi: 10.1152/physiolgenomics.00016.2002. Epub 2002 Dec 26.
PubMed 12407183
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Basis of Abdominal Aortic Aneurysm
- ClinicalTrials.gov ID
- NCT00005526
- Acronym / sponsor ID
- 5058
- Study type
- Observational
- Recruitment status
- Completed
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Aug 1991
- Study completion
- Nov 2001 (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 identify the genetic (major genes) and environmental factors responsible for the significant aggregation of abdominal aortic aneurysm (AAA) among relatives of affected individuals.
Detailed description
BACKGROUND:
Abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta which can, if undetected, lead to rupture. The mortality associated with ruptured AAA is estimated to be 90 percent, while elective repair has a mortality risk of approximately 6 percent. Ruptured AAA is a leading cause of death among older Americans. The identification of markers of AAA risk could lead to preventive intervention. AAA aggregates in families, and segregation analysis shows that familial risk of AAA is best explained by the segregation of a major gene with an autosomal recessive mode of inheritance.
DESIGN NARRATIVE:
Affected relative pairs (primarily sibling pairs) with AAA and no evidence of a family history of a connective tissue disorder were genotyped for 150 highly informative microsatellite polymorphisms marking the autosomal genome at a resolution of 20 cM. The linkage between AAA and these loci was tested using robust affected pedigree member methods to identify genomic regions which might contain genes that predisposed individuals to develop AAA. The existence of predisposing gene(s) were confirmed and their location refined using a defined search strategy, genotyping at increasing levels of resolution, and re-analysis of family data. The predisposing gene(s) were identified by a combination of saturation mapping and molecular analysis of candidate loci. The association of AAA with environmental measures was investigated to determine an equation for estimating risk for relatives of AAA patients based upon environmental measures and genotype. Power calculations based upon the number and structure of families already collected demonstrated the feasibility of identifying genes that predisposed to AAA using this strategy, even in the presence of significant heterogeneity with respect to the loci involved. In addition to identifying genes that were necessary for AAA by linkage analysis, a series of analyses of association were undertaken to identify true susceptibility genes that were neither necessary nor sufficient to cause disease, but which modified an individual's risk of developing AAA.
The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.
Study design
Who may qualify
- Ages
- Up to 100 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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
Not reported in the source record.
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 13 May 2016.
- Background: PubMed 10582986Peters DG, Kassam A, St Jean PL, Yonas H, Ferrell RE. Functional polymorphism in the matrix metalloproteinase-9 promoter as a potential risk factor for intracranial aneurysm. Stroke. 1999 Dec;30(12):2612-6. doi: 10.1161/01.str.30.12.2612.
- Background: PubMed 10572191Peters DG, Kassam AB, Yonas H, O'Hare EH, Ferrell RE, Brufsky AM. Comprehensive transcript analysis in small quantities of mRNA by SAGE-lite. Nucleic Acids Res. 1999 Dec 15;27(24):e39. doi: 10.1093/nar/27.24.e39.
- Background: PubMed 10374728Vorp DA, Peters DG, Webster MW. Gene expression is altered in perfused arterial segments exposed to cyclic flexure ex vivo. Ann Biomed Eng. 1999 May-Jun;27(3):366-71. doi: 10.1114/1.158.
- Background: PubMed 8666418St Jean P, Hart B, Webster M, Steed D, Adamson J, Powell J, Ferrell R. Alpha-1-antitrypsin deficiency in aneurysmal disease. Hum Hered. 1996 Mar-Apr;46(2):92-7. doi: 10.1159/000154333.
- Background: PubMed 7762981St Jean PL, Zhang XC, Hart BK, Lamlum H, Webster MW, Steed DL, Henney AM, Ferrell RE. Characterization of a dinucleotide repeat in the 92 kDa type IV collagenase gene (CLG4B), localization of CLG4B to chromosome 20 and the role of CLG4B in aortic aneurysmal disease. Ann Hum Genet. 1995 Jan;59(1):17-24. doi: 10.1111/j.1469-1809.1995.tb01602.x.
- Background: PubMed 7874138St Jean PL, Zhang XC, Hart BK, Ferrell RE. Dinucleotide repeat polymorphism at the HPR locus. Hum Mol Genet. 1994 Nov;3(11):2081. No abstract available.
- Background: PubMed 8368807Foster K, Ferrell R, King-Underwood L, Povey S, Attwood J, Rennick R, Humphries SE, Henney AM. Description of a dinucleotide repeat polymorphism in the human elastin gene and its use to confirm assignment of the gene to chromosome 7. Ann Hum Genet. 1993 May;57(2):87-96. doi: 10.1111/j.1469-1809.1993.tb00890.x.
- Background: PubMed 11283408Peters DG, Kassam AB, Feingold E, Heidrich-O'Hare E, Yonas H, Ferrell RE, Brufsky A. Molecular anatomy of an intracranial aneurysm: coordinated expression of genes involved in wound healing and tissue remodeling. Stroke. 2001 Apr;32(4):1036-42. doi: 10.1161/01.str.32.4.1036.
- Background: PubMed 12407183Peters DG, Zhang XC, Benos PV, Heidrich-O'Hare E, Ferrell RE. Genomic analysis of immediate/early response to shear stress in human coronary artery endothelial cells. Physiol Genomics. 2002 Dec 26;12(1):25-33. doi: 10.1152/physiolgenomics.00016.2002. Epub 2002 Dec 26.
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.
Robert Ferrell
University of Pittsburgh
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Diseases and Heart Diseases, run by National Heart, Lung, and Blood Institute (NHLBI).
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 13 May 2016. Status can change between updates, so confirm with the study contact before making plans.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005526, which also lists 9 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 13 May 2016.