Clinical trial NCT01764529: Modifiers of Disease Severity in Cerebral Cavernous Malformations
Official title: Modifiers of Disease Severity and Progression in Cerebral Cavernous Malformations
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Cavernous Angioma, Familial
Cerebral Cavernous Malformations
Cerebral Cavernous Hemangioma
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: University of New Mexico
name: University of Chicago
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Boston Children's Hospital
name: Children's Hospital Medical Center, Cincinnati
name: Barrow Neurological Institute
name: Alliance to Cure Cavernous Malformation
First posted: 2013-01-09
Enrollment: 800
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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
* Identify 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 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.

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

Primary outcomes:
measure: Total CCM lesion number per patient
timeFrame: Baseline
measure: Rate of symptomatic hemorrhage
timeFrame: Baseline and annual assessment
Secondary outcomes:
measure: Change in lesion number
timeFrame: Baseline, Follow up MRI
measure: Modified Rankin score
timeFrame: Baseline and annual assessment
Other outcomes:
measure: Patient-Reported Quality of Life (QoL) (NIH PROMIS-29)
timeFrame: Baseline and annual assessment
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Chicago
country: United States
facility: University of Chicago, Medicine and Biological Sciences
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Albuquerque
country: United States
facility: University of New Mexico Health Sciences Center
state: New Mexico
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital, Division of Pediatric Neurosurgery, Cerebrovascular Program
state: Ohio
city: Charlottesville
country: United States
facility: Alliance to Cure Cavernous Malformation
state: Virginia
Study officials:
affiliation: University of California, San Francisco
name: Helen Kim, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Chicago
name: Issam Awad, MD
role: PRINCIPAL_INVESTIGATOR
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