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Cerebral Hemorrhage Risk in Hereditary Hemorrhagic Telangiectasia (BVMN6203)

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ClinicalTrials.gov Identifier: NCT01158807
Recruitment Status : Recruiting
First Posted : July 8, 2010
Last Update Posted : May 4, 2021
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Unity Health Toronto

Brief Summary:

This study is one of the three projects of an NIH Rare Disease Clinical Research Consortium. A "consortium" is a group of centres sharing information and resources to perform research. The consortium research focuses on brain blood vessel malformations in three different rare diseases.

The focus of this specific study is on Hemorrhagic Telangiectasia (HHT).

HHT is a condition characterized by blood vessel malformations, called telangiectasia and arteriovenous malformations (AVMs), occurring in the brain, nose, lungs, stomach, bowels and liver. Brain AVMs (BAVMs) in HHT are difficult to study because they are rare, affecting approximately 10% of people with HHT. While other types of BAVMs have been studied in depth, studies in the HHT population have been very small. Here, we propose the first large-scale collaboration by joining with 12 HHT Centers of Excellence in North America to perform a large study of risk factors for bleeding from BAVMs, called intracranial hemorrhage (ICH) in HHT patients.

The current standard of clinical practice across North America, is to screen all HHT patients for BAVMs with magnetic resonance imaging (MRI). If BAVMs are detected, patients are referred to a multidisciplinary neurovascular team for consideration for treatment. Treatment decisions are made on a case by case basis, balancing risks of complications from the BAVM with risks of therapy, but are limited by the few studies available in HHT. We hope that the knowledge we obtain about the risk factors for intracranial bleeding in these patients from this larger study will help us to improve the care of HHT patients.

We plan to study risk factors for rupture of BAVMs, including primarily genetics and imaging characteristics of the BAVMs. Knowledge about risk factors will help in the care and management of HHT patients. This will be achieved through the collection of health information to construct a HHT database, blood sampling and banking (through the National Institute of Neurological Disorders and Stroke [NINDS]), and through genetic analysis at the University of California San Francisco.


Condition or disease
Hereditary Hemorrhagic Telangiectasia

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Study Type : Observational
Estimated Enrollment : 1800 participants
Observational Model: Case-Control
Time Perspective: Other
Official Title: Cerebral Hemorrhage Risk in Hereditary Hemorrhagic Telangiectasia (RDCRN# 6203, Protocol Version Date 07Jan10)
Actual Study Start Date : April 8, 2010
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : September 2024


Group/Cohort
HHT- Brain Arteriovenous Malformation
  1. Definite clinical HHT diagnosis (at least 3 Curacao criteria) or genetic diagnosis of HHT and
  2. Presence of Brain Arteriovenous Malformation
HHT -NO BAVM
1. Definite clinical HHT diagnosis (at least 3 Curacao criteria) or genetic diagnosis of HHT



Primary Outcome Measures :
  1. Aim 1: The identification of predictors of brain outcomes in HHT patients [ Time Frame: Through study completion, an average of 5 years ]
    This study will investigate predictors of brain outcomes in HHT patients. The investigators hypothesize that the presence of brain arteriovenous malformation (BAVM) in HHT patients versus HHT patients without BAVM and multiplicity of BAVMs will be associated with worsening functional outcome. Therefore, the comprehensive brain outcomes in HHT for future HHT clinical trials will be characterized.


Secondary Outcome Measures :
  1. Aim 2: A severe bleeding phenotype in HHT will be defined for clinical trial readiness [ Time Frame: Through study completion, an average of 5 years ]
    The investigators hypothesize that weekly nasal bleeding duration in HHT will predict the need for invasive or life-sustaining therapies. HHT participant reported bleeding duration will be measured longitudinally and correlate with the need for invasive or life-sustaining therapies, as well as with ICH risk from BAVMs and with bleeding in other HHT organ phenotypes.

  2. Aim 3: The genetic predictors and circulating biomarkers of severe bleeding and brain outcomes in HHT will be characterized [ Time Frame: Through study completion, an average of 5 years ]
    The investigators hypothesize that there are shared predictors of severe bleeding from the nose and brain in HHT patients, and that identifying these predictors will allow for selection of "at-risk" patients for clinical trials. Specifically, potential genetic, plasma protein biomarker and circulating miRNA biomarker predictors of bleeding will be evaluated. Markers associated with bleeding will then be tested for association with ICH, and with other brain outcomes and HHT severity phenotypes.


Biospecimen Retention:   Samples With DNA
blood and/or saliva


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
HHT individuals with a history of brain arteriovenous malformation. HHT individuals without a history of brain arteriovenous malformation.
Criteria

Inclusion criteria:

  • Definite clinical HHT diagnosis (at least 3 Curacao criteria)or genetic diagnosis of HHT or
  • Definite clinical HHT diagnosis (at least 3 Curacao criteria) or genetic diagnosis of HHT and Presence of Brain Arteriovenous Malformation
  • Able to provide informed consent

Curacao criteria:

  1. spontaneous recurrent nosebleeds;
  2. mucocutaneous telangiectasia at characteristic sites (lips, oral cavity or the nose);
  3. visceral involvement such as pulmonary, hepatic or CNS BAVM; and (d) an affected first degree relative by same criteria.

Willingness

  • Willingness to participate in the study and ability to give informed consent

Exclusion Criteria:

  • Patients not complying with Inclusion criteria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01158807


Contacts
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Contact: Marie Faughnan, MD 416-864-6060 ext 5412 marie.faughnan@unityhealth.to
Contact: Dewi Clark, MHSc 416-864-6060 ext 42887 dewi.clark@unityhealth.to

Locations
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Sponsors and Collaborators
Unity Health Toronto
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Marie Faughnan, MD MSc FRCPC Unity Health Toronto
Additional Information:
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Responsible Party: Unity Health Toronto
ClinicalTrials.gov Identifier: NCT01158807    
Other Study ID Numbers: RDCRN# 6203
1U54NS065705 ( U.S. NIH Grant/Contract )
First Posted: July 8, 2010    Key Record Dates
Last Update Posted: May 4, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Unity Health Toronto:
Hereditary Hemorrhagic Telangiectasia
Cerebral arteriovenous malformations
Additional relevant MeSH terms:
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Cerebral Hemorrhage
Telangiectasis
Telangiectasia, Hereditary Hemorrhagic
Hemorrhage
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Hemostatic Disorders
Hemorrhagic Disorders
Hematologic Diseases
Vascular Malformations
Cardiovascular Abnormalities
Congenital Abnormalities
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases