Cerebral Hemorrhage Risk in Hereditary Hemorrhagic Telangiectasia

NCT01158807 | Completed

• 2 other identifiers: RDCRN# 62031U54NS065705
• Study Type: observational
• Target: 2,272
• Locations: 3 countries
• Sites: 19

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.

Conditions

Hereditary Hemorrhagic Telangiectasia

Keywords

Hereditary Hemorrhagic Telangiectasia; Cerebral arteriovenous malformations

Outcome Measures

Primary Outcomes (1)

• Aim 1: The identification of predictors of brain outcomes in HHT patients

  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.

  Through study completion, an average of 5 years

Secondary Outcomes (2)

• Aim 2: A severe bleeding phenotype in HHT will be defined for clinical trial readiness

  Through study completion, an average of 5 years

• Aim 3: The genetic predictors and circulating biomarkers of severe bleeding and brain outcomes in HHT will be characterized

  Through study completion, an average of 5 years

Study Arms (2)

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

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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:
• spontaneous recurrent nosebleeds;
• mucocutaneous telangiectasia at characteristic sites (lips, oral cavity or the nose);
• 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

Sponsors & Collaborators

• Unity Health Toronto: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (19)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

David Geffen School of Medicine at University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94110, United States

Location

UCHealth Pulmonary Vascular Disease Clinic - Anschutz Medical

Aurora, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06520-8042, United States

Location

Georgia Regents University

Augusta, Georgia, 30912-3135, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

HHT Foundation International, Inc.

Monkton, Maryland, 21111, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, NC, North Carolina, 27599, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

St. Paul's Hospital, University of British Columbia

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

St. Antonius Hospital

Nieuwegein, 3435, Netherlands

Location

Related Links

• This is the Rare Diseases Clinical Research Networkweb site which lists the BVMC 6203 HHT study

Biospecimen

Retention: SAMPLES WITH DNA

blood and/or saliva

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic; Intracranial Arteriovenous Malformations

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Telangiectasis; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Malformations; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Central Nervous System Vascular Malformations; Nervous System Malformations; Arteriovenous Malformations; Intracranial Arterial Diseases

Study Officials

• Marie Faughnan, MD MSc FRCPC

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2010
• First Posted: July 8, 2010
• Study Start: April 8, 2010
• Primary Completion: April 1, 2025
• Study Completion: June 30, 2025
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

NL (1); US (14); CA (4)