Modifiers of Disease Severity in Cerebral Cavernous Malformations

December 19, 2023 updated by: University of California, San Francisco

Modifiers of Disease Severity and Progression in Cerebral Cavernous Malformations

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
  • Identify blood biomarkers predictive of CCM disease severity and progression for clinical trials.

Study Overview

Status

Recruiting

Conditions

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.

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

Enrollment (Estimated)

800

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Arizona
    • California
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California, San Francisco
        • Contact:
        • Principal Investigator:
          • Helen Kim, PhD
        • Sub-Investigator:
          • Nerissa U. Ko, MD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago, Medicine and Biological Sciences
        • Contact:
        • Contact:
        • Principal Investigator:
          • Issam Awad, MD
    • Massachusetts
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • Recruiting
        • University of New Mexico Health Sciences Center
        • Principal Investigator:
          • Michel Torbey, MD
        • Contact:
        • Sub-Investigator:
          • Marc Mabray, MD
        • Contact:
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital, Division of Pediatric Neurosurgery, Cerebrovascular Program
        • Contact:
        • Contact:
        • Principal Investigator:
          • Sudhakar Vadivelu, DO
    • Virginia
      • Charlottesville, Virginia, United States, 22901
        • Active, not recruiting
        • Alliance to Cure Cavernous Malformation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
The BVMC FCCM cohort

Aim 1: To investigate the relationship between lesion burden and outcomes in familial CCM.

Aim 2: To investigate the role of the gut microbiome in familial CCM disease severity.

Aim 3: To establish blood markers predictive of disease severity and progression for medical treatment of CCM.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline
Rate of symptomatic hemorrhage
Time Frame: Baseline and annual assessment
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 hemorrhage rates will be assessed.
Baseline and annual assessment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, Follow up MRI
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
Baseline and annual assessment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient-Reported Quality of Life (QoL) (NIH PROMIS-29)
Time Frame: Baseline and annual assessment
Standardized patient reported outcome measurement tools to assess pain, fatigue, physical function, emotional distress, and social participation.
Baseline and annual assessment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

University of Chicago
National Institute of Neurological Disorders and Stroke (NINDS)
Boston Children's Hospital
Children's Hospital Medical Center, Cincinnati
University of New Mexico
Barrow Neurological Institute
Alliance to Cure Cavernous Malformation

Investigators

  • Principal Investigator: Issam Awad, MD, University of Chicago
  • Principal Investigator: Helen Kim, PhD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 27, 2010

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

January 7, 2013

First Submitted That Met QC Criteria

January 7, 2013

First Posted (Estimated)

January 9, 2013

Study Record Updates

Last Update Posted (Actual)

December 26, 2023

Last Update Submitted That Met QC Criteria

December 19, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BVMC 6201
  • U54NS065705 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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