Modifiers of Disease Severity in Cerebral Cavernous Malformations

Sponsor

University of California, San Francisco (Other)

Overall Status

Recruiting

CT.gov ID

NCT01764529

Collaborator

University of New Mexico (Other), University of Chicago (Other), National Institute of Neurological Disorders and Stroke (NINDS) (NIH), Boston Children's Hospital (Other), Children's Hospital Medical Center, Cincinnati (Other), Barrow Neurological Institute (Other), Angioma Alliance (Other)

800

Enrollment

Locations

185

Anticipated Duration (Months)

114.3

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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.

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:

Clinical diagnosis of CCM,
Multi-focal lesions on MRI, and/or
Family history of CCMs.

Exclusion Criteria:

Patients who cannot or are unwilling to sign informed consent and for whom no appropriate surrogate is available.
Prisoners and homeless individuals because of the inability to contact the subject and collect follow-up data using standard procedures.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

800 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Modifiers of Disease Severity and Progression in Cerebral Cavernous Malformations

Actual Study Start Date :

Jul 1, 2009

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
The BVMC FCCM cohort 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.

Outcome Measures

Primary Outcome Measures

Total CCM lesion number per patient [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.
Rate of symptomatic hemorrhage [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 hemorhrage rates will be assessed.

Secondary Outcome Measures

Change in lesion number [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.
Modified Rankin score [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

Patient-Reported Quality of Life (QoL) (The NIH PROMIS-29) [Baseline and annual assessment]
Standardized patient reported outcome measurement tools to assess pain, fatigue, physical function, emotional distress, and social participation.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Individual has a CCM mutation confirmed through DNA testing, or
Individual meets 2 or more of the following clinical criteria:

Clinical diagnosis of CCM
Multi-focal CCMs on MRI
Family history of CCM

Exclusion Criteria:

Individuals who are incarcerated
Individuals who are homeless
Unable or unwilling to sign the informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barrow Neurological Institute	Phoenix	Arizona	United States	85013
2	University of California, San Francisco	San Francisco	California	United States	94143
3	University of Chicago, Medicine and Biological Sciences	Chicago	Illinois	United States	60637
4	Boston Children's Hospital	Boston	Massachusetts	United States	02115
5	University of New Mexico Health Sciences Center	Albuquerque	New Mexico	United States	87131
6	Angioma Alliance	Durham	North Carolina	United States	27713
7	Cincinnati Children's Hospital, Division of Pediatric Neurosurgery, Cerebrovascular Program	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

University of California, San Francisco
University of New Mexico
University of Chicago
National Institute of Neurological Disorders and Stroke (NINDS)
Boston Children's Hospital
Children's Hospital Medical Center, Cincinnati
Barrow Neurological Institute
Angioma Alliance

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

University of California, San Francisco

ClinicalTrials.gov Identifier:

NCT01764529

Other Study ID Numbers:

BVMC 6201
U54NS065705

First Posted:

Jan 9, 2013

Last Update Posted:

Feb 24, 2022

Last Verified:

Feb 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Hemangioma

Hemangioma, Cavernous, Central Nervous System

Hemangioma, Cavernous

Congenital Abnormalities

Study Results

No Results Posted as of Feb 24, 2022