Aortopathy in Persons With Bicuspid Aortic Valve, Turner and Marfan Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by University of Aarhus
Sponsor:
Information provided by (Responsible Party):
University of Aarhus
ClinicalTrials.gov Identifier:
NCT01760668
First received: January 2, 2013
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

The study aim is:

  1. To examine aortic tissue by light microscopy
  2. To examine aortic tissue by electron microscopy
  3. To study changes in the epigenome and transcriptome of the X chromosome specific to aortic tissue.
  4. To examine aortic tissue using biochemistry including proteomics.
  5. To establish the karyotype of fibroblasts with standard chromosome examination on 10 meta-phases as well as by fluorescent in situ hybridization (FISH) with probes covering the X and Y chromosome. Using the latter 200 meta-phases will be examined.

30 controls who did not die from aortic dissection or dilation will be recruited from The Department of Forensic Medicine at Aarhus University Hospital.

The investigators will subject samples of aortic tissue from women undergoing prophylactic aortic surgery due to either Marfan syndrome or bicuspid aortic valve to the same panel of examinations (except karyotyping). Lastly the investigators will compare the results from the three groups (Turner syndrome, Marfan syndrome and Bicuspid aortic valve).


Condition
Turner Syndrome
Bicuspid Aortic Valve
Marfan Syndrome

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Aortopathy in Persons With Bicuspid Aortic Valve, Turner and Marfan Syndrome

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • Histone modifications [ Time Frame: Cross sectional ] [ Designated as safety issue: No ]
    Permissive and repressive histone modifications on the X-chromosome

  • mRNA and non-coding RNAs [ Time Frame: Cross sectional ] [ Designated as safety issue: No ]
    Identification of the entire transcriptome including both mRNA and non-coding RNAs (lincRNA as well as miRNA)from the X-chromosome

  • DNA-methylations of CpG-islands [ Time Frame: Cross sectional ] [ Designated as safety issue: No ]
    mapping DNA-methylations of CpG-islands

  • Electron microscopic evaluation [ Time Frame: Cross sectional ] [ Designated as safety issue: No ]
  • Karyotyping by FISH and conventional karyotyping [ Time Frame: Cross sectional ] [ Designated as safety issue: No ]
  • Proteomics [ Time Frame: Cross sectional ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Aortic tissue

Blood Serum


Estimated Enrollment: 60
Study Start Date: February 2013
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Turner syndrome (TS)
TS verified by genotyping Age > 18 years awaiting operation due to aortic dilation
Marfan syndrome (MS)
Females with MS verified clinically or by genotyping Age > 18 years awaiting operation due to aortic dilation
Bicuspid aortic valve
females with bicuspid aortic valve Age > 18 years awaiting operation due to aortic dilation
Controls
Men/females who died from conditions other than aortic dilation or dissection. Age 20-60 years.

Detailed Description:

Turner syndrome is a congenital complete or partial lack of one of the female sex chromosomes affecting 1 of 2000 live born girls. The syndrome is characterized by an increased prevalence of ischemic heart disease, aortic dilation and dissection, hypertension, stroke and autoimmune diseases in general.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Individuals with Turner syndrome will be recruited from out-patient clinics. Individuals with Turner syndrome, Marfan syndrome and bicuspid aortic valve will be recruited from departments of cardiology or thoracic surgery in Odense, Copenhagen or Aarhus (Denmark).

Criteria

Turner syndrome (TS).

A. Inclusion

  • TS verified by genotyping
  • Age > 18 years
  • Awaiting operation due to aortic dilation

B. Exclusion - Previous aortic dissection or operation of the aorta (per-cutaneous or open surgery)

Marfan syndrome (MS)

A. Inclusion

  • Females with MS verified clinically or by genotyping
  • Age > 18 years
  • Awaiting operation due to aortic dilation

B. Exclusion

- Previous aortic dissection or operation of the aorta (per-cutaneous or open surgery)

Bicuspid aortic valve

A. Inclusion

  • Females with Bicuspid aortic valve
  • Age > 18 years
  • Awaiting operation due to aortic dilation

B. Exclusion - Previous aortic dissection or operation of the aorta (per-cutaneous or open surgery)

Controls

A. Inclusion

  • Men/females who died from conditions other than aortic dilation or dissection.
  • Age 20-60 years.

B. Exclusion

- Previous aortic dissection or operation of the aorta (per-cutaneous or open surgery)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01760668

Contacts
Contact: Christian Trolle, MD +4561339269 Christian.Trolle@KI.AU.DK
Contact: Claus H Gravholt, MD, PhD +45 7846 9977 claus.gravholt@ki.au.dk

Locations
Denmark
Department of Endocrinology and Internal medicine Recruiting
Aarhus C, Denmark, 8000
Contact: Christian Trolle, MD    +4561339269    Christian.Trolle@KI.AU.DK   
Contact: Christian Trolle, MD    +4561339269    christian.trolle@ki.au.dk   
Principal Investigator: Christian Trolle, MD         
Sponsors and Collaborators
University of Aarhus
Investigators
Principal Investigator: Christian Trolle Aarhus University Hospital
Study Director: Claus H Gravholt, MD, Ph.d. Aarhus University Hospital
  More Information

No publications provided

Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT01760668     History of Changes
Other Study ID Numbers: 1-10-72-561-12
Study First Received: January 2, 2013
Last Updated: March 18, 2013
Health Authority: Denmark: Ethics Committee
Denmark: Danish Dataprotection Agency

Keywords provided by University of Aarhus:
Sex chromosome
Turner Syndrome
Marfan syndrome
Bicuspid aortic valve
Aortic Aneurysm
Epigenetics
Transcriptome
non-coding RNA
Electron microscopy
Proteomics

Additional relevant MeSH terms:
Arachnodactyly
Marfan Syndrome
Aortic Valve Stenosis
Gonadal Dysgenesis
Heart Valve Diseases
Primary Ovarian Insufficiency
Syndrome
Turner Syndrome
Abnormalities, Multiple
Adnexal Diseases
Bone Diseases
Bone Diseases, Developmental
Cardiovascular Abnormalities
Cardiovascular Diseases
Chromosome Disorders
Congenital Abnormalities
Connective Tissue Diseases
Disease
Disorders of Sex Development
Endocrine System Diseases
Genetic Diseases, Inborn
Genital Diseases, Female
Gonadal Disorders
Heart Defects, Congenital
Heart Diseases
Limb Deformities, Congenital
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Ovarian Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on October 22, 2014