Results from a 12-month Natural History Study of Patients with Cerebral Cavernous Malformations
Chad Heatwole1, Jamison Seabury1, Anika Varma1, Spencer Rosero2, Charlotte Engebrecht1, Shaweta Khosa1, Christina Shupe1, Charlotte Irwin1, John Heatwole3, Christine Zizzi1, Danae Alexandrou4, Nuran Dilek5, Roshawn Watson6, Holly Blei7, Cornelia Lee7, Jennifer Weinstein1
1University of Rochester Center for Health + Technology, 2The University of Utah Spencer Fox Eccles School of Medicine, 3Cornell University, College of Agriculture and Life Sciences, 4Loyola University of Chicago, Stritch School of Medicine, 5University of Rochester, 6Recursion Pharmaceuticals, Inc., 7Alliance to Cure Cavernous Malformation
Objective:
To evaluate multifactorial disease progression in a diverse population of patients with cerebral cavernous malformations and to identify which factors are associated with a faster or slower progression of disease.
Background:
In order to facilitate therapeutic studies in CCM, it is necessary to: 1) understand the natural history of CCM; 2) predict which patients will have the fastest disease progression; and, 3) determine the performance metrics of outcome measures designed to measure disease burden overtime.
Design/Methods:
We conducted a 12-month prospective observational study of adults with CCM who were assessed at baseline, 6 months, and 12 months. Participants serially completed the regulatory-grade Cerebral Cavernous Malformation - Health Index (CCM-HI) and the SymptoMScreen at each time point. In addition, participants completed a survey preference questionnaire at baseline, and global impression of change questionnaires at 6 and 12 months. Minimal clinically important difference (MCID) values were assessed using anchor-based methodology. CCM-HI scores were analyzed by demographic subgroups and participants’ preferences for the CCM-HI versus the SymptoMScreen was determined.
Results:
Three-hundred and sixty-one adults with CCM representing 23 countries participated in this study. Participants with higher disability levels and younger age had a faster progression of disease in some CCM-HI subscales and males experienced a faster disease progression of headaches compared to females. The weighted average MCID of the CCM-HI total score (0-100) from baseline to 12 months was 2.5 points. Seventy-seven point five percent of our cohort preferred the CCM-HI over the SymptoMScreen as a clinical trial outcome measure.
Conclusions:
Disease progression is slow in CCM but can be tracked using the CCM-HI. Select subgroups demonstrate a faster progression of disease as measured by CCM-HI subscales. CCM-HI performance metrics generated through this study can help facilitate the planning and interpretation of future therapeutic trials in CCM.