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Modifiers of Disease Severity in Cerebral Cavernous Malformations

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ClinicalTrials.gov Identifier: NCT01764529
Recruitment Status : Recruiting
First Posted : January 9, 2013
Last Update Posted : August 8, 2019
Sponsor:
Collaborators:
Barrow Neurological Institute
Angioma Alliance
National Institute of Neurological Disorders and Stroke (NINDS)
University of New Mexico
National Center for Advancing Translational Science (NCATS)
Information provided by (Responsible Party):
Helen Kim, MPH, PhD, University of California, San Francisco

Brief Summary:

Cerebral cavernous malformations (CCMs) are clusters of abnormal blood vessels in the brain and spine. CCMs can bleed and cause strokes, seizures, and headaches. CCMs are often caused by an inherited gene mutation (alteration) in one of three CCM genes (CCM1, CCM2, or CCM3). There is a wide range of disease severity even among family members with this disease, though the natural history has not been clearly described for this particular population.

This study will continue to enroll and follow participants with familial CCM to identify factors that influence CCM disease severity and progression, focusing on barriers to clinical trial preparedness. Our long-term goal is to identify measurable outcomes and robust biomarkers that will help select high-risk patients and help monitor drug response in future clinical trials. The specific goals of this study are to:

  1. identify factors that influence lesion progression to symptomatic hemorrhage and other outcomes, including quality of life;
  2. investigate the role of the gut microbiome and lesion burden in CCM disease; and
  3. establish blood biomarkers predictive of CCM disease severity and progression for clinical trials.

Condition or disease
Cavernous Angioma, Familial Cerebral Cavernous Malformations Cerebral Cavernous Hemangioma

Detailed Description:

This study is one of three projects participating in the Brain Vascular Malformation Consortium (BVMC) funded by the Office of Rare Diseases Research, which is part of the National Center for Advancing Translational Sciences (NCATS), and the National Institute of Neurological Disorders and Stroke (NINDS). The CCM project is a cross-sectional and longitudinal study of familial CCM patients. The study is currently in the third 5-year cycle. During the first 5 year cycle (BVMC1), the CCM project was focused on recruiting CCM1 cases with the common Hispanic mutation (CHM). In the second 5-year cycle (BVMC2), we expanded recruitment to include not only CCM1-CHM cases, but also other CCM familial patients and mutation carriers. In the third 5-year cycle (BVMC3), we will continue to recruit familial CCM cases and expand to additional recruitment sites. We collect clinical, genetic, imaging, treatment, and outcome data in participants, and follow enrolled participants over time to understand the natural history of this disease.

For new study participants, you will be asked to:

  • Give permission for study staff to access your medical records to collect clinical information and to obtain copies of MRI scans and reports
  • Fill out a questionnaire about your quality of life, family history, and medical/surgical history
  • Give a blood and/or saliva sample, and stool sample
  • Give permission to store and use your CCM resected tissue for research (if undergoing surgery)
  • Participate in annual follow-ups to update medical, surgical, and neurological information

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 800 participants
Observational Model: Cohort
Time Perspective: Other
Target Follow-Up Duration: 15 Years
Official Title: Modifiers of Disease Severity and Progression in Cerebral Cavernous Malformations
Study Start Date : July 2009
Estimated Primary Completion Date : July 2024
Estimated Study Completion Date : July 2024


Group/Cohort
CCM Participants

Have a confirmed diagnosis of familial CCM by DNA testing, or meet 2 of the 3 following criteria:

  • Clinical diagnosis of CCM
  • Evidence of multiple cavernous malformations on MRI
  • Someone in your immediate or extended family has a clinical diagnosis of CCM



Primary Outcome Measures :
  1. Total CCM lesion number per patient [ Time Frame: Baseline ]
    The number of lesions (or cavernous angiomas) located in the brain will be counted by a neuroradiologist and by an automated algorithm developed as part of this project.

  2. Rate of symptomatic hemorrhage [ Time Frame: Baseline and annual asessment ]
    Symptomatic hemorrhage is defined as diagnostic evidence of new lesional bleeding or hemorrhagic growth, in association with directly attributable symptoms. Rate of symptomatic hemorrhage and the factors that influence hemorhrage rates will be assessed.


Secondary Outcome Measures :
  1. Change in lesion number [ Time Frame: Baseline, Follow up MRI ]
    The number of lesions (or cavernous angiomas) counted on the baseline MRI will be compared to the number of lesions observed in follow up MRIs.

  2. Modified Rankin score [ Time Frame: Baseline and annual assessment ]
    The modified Rankin score will be assessed at baseline and at approximately one year intervals while remaining in study


Other Outcome Measures:
  1. Patient-Reported Outcomes Measurement Information System (PROMIS) [ Time Frame: Baseline and annual assessment ]
    Standardized patient reported outcome measurement tools to assess pain, fatigue, physical function, emotional distress, and social participation.


Biospecimen Retention:   Samples With DNA
We collect and store saliva as well as whole blood for DNA, RNA, and plasma or serum samples. Brain cavernous malformation tissue will be collected and banked as available.


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
The study population includes individuals who carry the diagnosis of familial cerebral cavernous malformation (CCM), both symptomatic and asymptomatic.
Criteria

Inclusion Criteria:

  • Have a confirmed diagnosis of familial CCM by DNA testing, or
  • Meet 2 of the 3 following criteria:

    • Clinical diagnosis of familial CCM
    • Evidence of multiple cavernous malformations on MRI
    • Someone in your immediate or extended family has a clinical diagnosis of CCM

Exclusion Criteria:

  • Incarceration
  • Homeless

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): NCT01764529


Contacts
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Contact: Helen Kim, PhD 415-206-8906 helen.kim2@ucsf.edu
Contact: Atif Zafar, MD 505 272-3194 azafar@salud.unm.edu

Locations
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United States, Arizona
Barrow Neurological Institute Recruiting
Phoenix, Arizona, United States, 85013
Contact: Norissa Honea    602-406-6267    Norissa.Honea@DignityHealth.org   
Sub-Investigator: Joseph Zabramski, MD         
Principal Investigator: Michael T. Lawton, MD         
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Avery Lui    415-476-2680    avery.lui@ucsf.edu   
Contact: Helen Kim, PhD    415-206-8906    helen.kim2@ucsf.edu   
Principal Investigator: Helen Kim, PhD         
United States, New Mexico
University of New Mexico Health Sciences Center Recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Atif Zafar, MD    505-272-3194    azafar@salud.unm.edu   
Contact: Myranda B Robinson, BS    505 272-3194    MBRobinson@salud.unm.edu   
Principal Investigator: Atif Zafar, MD         
Sub-Investigator: Marc Mabray, MD         
United States, North Carolina
Angioma Alliance Recruiting
Durham, North Carolina, United States, 27713
Contact: Amy L Akers, PhD    757-818-0403    Amy.Akers@angioma.org   
Sponsors and Collaborators
University of California, San Francisco
Barrow Neurological Institute
Angioma Alliance
National Institute of Neurological Disorders and Stroke (NINDS)
University of New Mexico
National Center for Advancing Translational Science (NCATS)
Investigators
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Principal Investigator: Atif Zafar, MD University of New Mexico
Principal Investigator: Marc Mabray, MD University of New Mexico
Principal Investigator: Helen Kim, PhD University of California, San Francisco
Principal Investigator: Amy Akers, PhD Angioma Alliance
Principal Investigator: Joseph Zabramski, MD Barrow Neurological Institute
Principal Investigator: Michael T. Lawton, MD Barrow Neurological Institute

Additional Information:
Publications:

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Responsible Party: Helen Kim, MPH, PhD, Leader, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01764529     History of Changes
Other Study ID Numbers: BVMC 6201
U54NS065705 ( U.S. NIH Grant/Contract )
First Posted: January 9, 2013    Key Record Dates
Last Update Posted: August 8, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Available data will be released to the Rare Diseases Clinical Research Network repository and will become available to the scientific community one year after publication of planned analyses, or after a period of 5 years from the date when the data were collected, whichever comes first

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Hemangioma
Hemangioma, Cavernous, Central Nervous System
Hemangioma, Cavernous
Congenital Abnormalities
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Central Nervous System Vascular Malformations
Nervous System Malformations
Nervous System Diseases
Vascular Malformations
Cardiovascular Abnormalities
Cardiovascular Diseases
Hemostatic Disorders
Vascular Diseases
Hemorrhagic Disorders
Hematologic Diseases