Modifiers of Disease Severity in Cerebral Cavernous Malformations

Brief Title

Modifiers of Disease Severity in Cerebral Cavernous Malformations

Official Title

Modifiers of Disease Severity and Progression in Cerebral Cavernous Malformations

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:

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

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

      Give a blood and/or saliva sample, and stool sample.

      Give permission to store and use your CCM resected tissue for research (if undergoing

      Participate in annual follow-ups to update medical, surgical, and neurological information.

      Eligible cases include those with a known genetic mutation in one of the three CCM genes or
      those that meet 2 of 3 following clinical criteria:

        1. Clinical diagnosis of CCM,

        2. Multi-focal lesions on MRI, and/or

        3. Family history of CCMs.

      Exclusion Criteria:

        1. Patients who cannot or are unwilling to sign informed consent and for whom no
           appropriate surrogate is available.

        2. Prisoners and homeless individuals because of the inability to contact the subject and
           collect follow-up data using standard procedures.

Study Type

Observational [Patient Registry]

Primary Outcome

Total CCM lesion number per patient

Secondary Outcome

 Change in lesion number


Cavernous Angioma, Familial

Study Arms / Comparison Groups

 The BVMC FCCM cohort
Description:  Aim 1: To investigate the relationship between lesion burden and outcomes in FCCM.
Aim 2: To investigate the role of the gut microbiome in FCCM disease severity. Aim 3: To establish blood markers predictive of disease severity and progression for medical treatment of CCM.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

July 2009

Completion Date

December 2024

Primary Completion Date

December 2024

Eligibility Criteria

        Inclusion Criteria:

          -  Individual has a CCM mutation confirmed through DNA testing, or

          -  Individual meets 2 or more of the following clinical criteria:

               1. Clinical diagnosis of CCM

               2. Multi-focal CCMs on MRI

               3. Family history of CCM

        Exclusion Criteria:

          1. Individuals who are incarcerated

          2. Individuals who are homeless

          3. Unable or unwilling to sign the informed consent




N/A - N/A

Accepts Healthy Volunteers



Helen Kim, PhD, 415-206-8906, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID

BVMC 6201

Secondary IDs


Responsible Party


Study Sponsor

University of California, San Francisco


 University of New Mexico

Study Sponsor

Helen Kim, PhD, Principal Investigator, University of California, San Francisco

Verification Date

December 2019