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 : September 22, 2020
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|
|Cavernous Angioma, Familial Cerebral Cavernous Malformations Cerebral Cavernous Hemangioma|
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.
- 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 Type :||Observational [Patient Registry]|
|Estimated Enrollment :||800 participants|
|Target Follow-Up Duration:||15 Years|
|Official Title:||Modifiers of Disease Severity and Progression in Cerebral Cavernous Malformations|
|Actual Study Start Date :||July 2009|
|Estimated Primary Completion Date :||December 2024|
|Estimated Study Completion Date :||December 2024|
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.
- 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.
- 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 hemorhrage rates will be assessed.
- 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.
- 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
- Patient-Reported Quality of Life (QoL) (The 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.
Biospecimen Retention: Samples With DNA
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
|Contact: Helen Kim, PhDemail@example.com|
|Contact: Andres Alvarez Pinzon, PhD, MDfirstname.lastname@example.org|
|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 email@example.com|
|Contact: Helen Kim, PhD 415-206-8906 firstname.lastname@example.org|
|Principal Investigator: Helen Kim, PhD|
|United States, Illinois|
|University of Chicago, Medicine and Biological Sciences||Recruiting|
|Chicago, Illinois, United States, 60637|
|Contact: Issam Awad, MD 773-702-8996 email@example.com|
|Contact: Agnieszka Stadnik, MS, CCRP (773) 702-8996 firstname.lastname@example.org|
|Principal Investigator: Issam Awad, MD|
|United States, Massachusetts|
|Boston Children's Hospital||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Tina Mounlavongsy, MPH, CDA 617-355-8310 email@example.com|
|Principal Investigator: Edward R. Smith, MD|
|United States, New Mexico|
|University of New Mexico Health Sciences Center||Recruiting|
|Albuquerque, New Mexico, United States, 87131|
|Contact: Michel Torbey, MD 505-272-3152 firstname.lastname@example.org|
|Contact: Jacquelyn S Morales 505 272-0356 JSMorales@salud.unm.edu|
|Principal Investigator: Michel Torbey, MD|
|Sub-Investigator: Marc Mabray, MD|
|United States, North Carolina|
|Angioma Alliance||Enrolling by invitation|
|Durham, North Carolina, United States, 27713|
|United States, Ohio|
|Cincinnati Children's Hospital, Division of Pediatric Neurosurgery, Cerebrovascular Program||Recruiting|
|Cincinnati, Ohio, United States, 45229|
|Contact: Ashton Roach, MS 513-803-7621 Ashton.Roach@cchmc.org|
|Contact: Sudhakar Vadivelu, DO 513-803-7621 Sudhakar.Vadivelu@cchmc.org|
|Principal Investigator: Sudhakar Vadivelu, DO|
|Principal Investigator:||Helen Kim, PhD||University of California, San Francisco|
|Principal Investigator:||Issam Awad, MD||University of Chicago|