CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness

Completed

Conditions: Cavernous Angioma
Cavernoma
Cerebral Cavernous Malformation
CCM
Cerebral Cavernous Malformations 1
Cerebral Cavernous Malformations 3
Cerebral Cavernous Malformations 2

Registration Number: NCT03652181

Lead Sponsor: University of Chicago

Brief Summary: Brain Cavernous Angiomas with Symptomatic Hemorrhage (CASH) are rare, but they exact a heavy burden of neurologic disability from recurrent bleeding, for which there is no proven therapy. This trial readiness project aims to address current critical obstacles in identifying cases at multiple sites, characterizing their relevant features, and measuring their outcome. The timing cannot be more opportune, with therapeutic targets already identified, exceptional collaboration among researchers and with the patient community, and several drugs ready to benefit from a track to clinical testing in the next five years.

Detailed Description: The Trial Readiness grant mechanism, funded by NINDS, proposes to address knowledge gaps and establish a research network as infrastructure for future research. This project includes an observational cohort study of 181 patients with an operational goal of demonstrating the feasibility of screening, enrollment rates, baseline disease categorization and follow-up of CASH using common data elements at multiple sites, and to assess the following endpoints for 123 participants enrolled at centers prespecified to do prospective follow-up: (1) the rates of recurrent hemorrhage; (2) the reliability of imaging biomarkers including quantitative susceptibility mapping and permeability measures which have been shown to correlate with lesion activity, and (3) change in functional status during prospective follow-up.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 123

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Rate of Recurrent Symptomatic Hemorrhage During the Two Year Follow-up Period in Patients With CASH.	2 year	Number of new bleeds reported during the two year follow-up period in the cohort with CASH. We will assess the change in the number of new symptomatic hemorrhage from baseline to year 1 and year 1 to year 2 follow-up.

Secondary Outcome Measures

Name	Time	Method
Median Score of European Quality of Life Visual Analogue Scale (EQ-VAS) During the 2 Year Follow-up Period.	2 years of follow-up	Median score of European Quality of Life Visual Analogue Scale (EQ-VAS) at baseline, year 1, year 2. The EQ-VAS is a vertical visual analogue scale that takes values between 100 (best imaginable health) and 0 (worst imaginable health), on which patients provide a global assessment of their health.
Percent Change in QSM Value (Lesional Iron Content)	2 years of follow-up	Change in QSM value (lesional iron content) will be presented as a mean value across all participants from baseline to year 1 and year 1 to year 2 follow-up MRIs
Percent Change in Contrast-enhanced Quantitative Perfusion (DCEQP) Value (Vascular Permeability)	2 years of follow-up	Change in DCEQP value (vascular permeability) will be presented as a mean value across all participants from baseline to year 1 and year 1 to year 2 follow-up MRIs
Compare the Number of Patients With MRS 2 or Higher Who Had Prospective Symptomatic Hemorrhage to Those With MRS 2 or Higher Without Prospective Symptomatic Hemorrhage During the 2 Year Follow-up Period.	2 years of follow-up	Compare the number of patients with MRS 2 or higher who had prospective symptomatic hemorrhage to those with MRS 2 or higher without prospective symptomatic hemorrhage from baseline to year 1 and year 1 to year 2 follow-up periods. The mRS is a simple global measure of functional disability. Scores range from 0 (no symptoms) to 6 (death). An mRS score of 0 to 1 is considered a minimal clinical disability, and 0 to 2 is independent.
Proportion of Patients With No Problems, Mild Problems, or Severe Problems in the "Self-care" Domain of European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3 L) During the 2 Year Follow-up Period.	2 years of follow-up	Proportion of patients with no problems, mild problems, or severe problems in the "Self-care" domain of EQ-5D-3 L will be assessed at baseline, year 1, and year 2 follow-up periods. EQ-5D-3 L is a generic tool for Patient Reported Outcomes (PRO) measurement that can assess patients' quality of life, irrespective of the disease and includes 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. There are 3 questions per domain where patients respond if they have no problems, mild, or severe problems.
Median T-score for "Fatigue" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.	2 years of follow-up	Median T-score for "Fatigue" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) at baseline, year 1, and year 2. PROMIS-29 (Version 2.0) is a generic health-related quality of life measure including 7 domains (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities).12 Each domain contains questions ranked using a 5-point Likert scale. PROMIS-29 domain scores are converted to T scores and have been standardized to a reference population (mean, 50; SD, 10). Clinically meaningful change is considered to be at least half the SD (5 points). Higher T-score indicates better outcome.
Median T-score for "Pain" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.	2 years of follow-up	Median T-score for "Pain" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) at baseline, year 1 and year 2. PROMIS-29 (Version 2.0) is a generic health-related quality of life measure including 7 domains (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities).12 Each domain contains questions ranked using a 5-point Likert scale. PROMIS-29 domain scores are converted to T scores and have been standardized to a reference population (mean, 50; SD, 10). Clinically meaningful change is considered to be at least half the SD (5 points). Higher T-score indicates better outcome.
Median T-score for "Physical Function" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.	2 years of follow-up	Median T-score for "Physical Function" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) at baseline, year 1 and year 2. PROMIS-29 (Version 2.0) is a generic health-related quality of life measure including 7 domains (anxiety, depression, fatigue, pain interference, sleep disturbance, and ability to participate in social roles and activities, and physical function).12 Each domain contains questions ranked using a 5-point Likert scale. PROMIS-29 domain scores are converted to T scores and have been standardized to a reference population (mean, 50; SD, 10). Clinically meaningful change is considered to be at least half the SD (5 points). Higher T-score indicates better outcome.
Median T-score for "Depression" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.	2 years of follow-up	Median T-score for "Depression" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) at baseline, year 1, and year 2. PROMIS-29 (Version 2.0) is a generic health-related quality of life measure including 7 domains (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities).12 Each domain contains questions ranked using a 5-point Likert scale. PROMIS-29 domain scores are converted to T scores and have been standardized to a reference population (mean, 50; SD, 10). Clinically meaningful change is considered to be at least half the SD (5 points). Higher T-score indicates better outcome.
Percentage of Patients With National Institutes of Health Stroke Scale (NIHSS) 0-4, 5-14 and 14+ During the 2 Year Follow-up Period.	2 years of follow-up	Percentage of patients with National Institutes of Health Stroke Scale (NIHSS) 0-4, 5-14 and 14+ from baseline to year 1 and year 1 to year 2 follow-up periods. NIHSS values range from 0 to 42, with stroke severity categorized as mild (0 to 4), moderate (5 to 14), severe (15 to 24), and very severe (≥25). 4-point decline in ischemic stroke clinical trials typically measures functional decline.
Median T-score for "Anxiety" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.	2 years of follow-up	Median T-score for "Anxiety" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) at baseline, year 1 and year 2. PROMIS-29 (Version 2.0) is a generic health-related quality of life measure including 7 domains (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities).12 Each domain contains questions ranked using a 5-point Likert scale. PROMIS-29 domain scores are converted to T scores and have been standardized to a reference population (mean, 50; SD, 10). Clinically meaningful change is considered to be at least half the SD (5 points). Higher T-score indicates better outcome.
Median T-score for "Sleep Disturbance" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.	2 years of follow-up	Median T-score for "Sleep Disturbance" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) at baseline, year 1 and year 2. PROMIS-29 (Version 2.0) is a generic health-related quality of life measure including 7 domains (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities).12 Each domain contains questions ranked using a 5-point Likert scale. PROMIS-29 domain scores are converted to T scores and have been standardized to a reference population (mean, 50; SD, 10). Clinically meaningful change is considered to be at least half the SD (5 points). Higher T-score indicates better outcome.
Proportion of Patients With No Problems, Mild Problems, or Severe Problems in the "Mobility" Domain of European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3 L) During the 2 Year Follow-up Period.	2 years of follow-up	Proportion of patients with no problems, mild problems, or severe problems in the "Mobility" domain of EQ-5D-3 L will be assessed at baseline, year 1, and year 2 follow-up periods. EQ-5D-3 L is a generic tool for Patient Reported Outcomes (PRO) measurement that can assess patients' quality of life, irrespective of the disease and includes 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. There are 3 questions per domain where patients respond if they have no problems, mild, or severe problems.
Proportion of Patients With No Problems, Mild Problems, or Severe Problems in the "Usual Activities" Domain of European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3 L) During the 2 Year Follow-up Period.	2 years of follow-up	Proportion of patients with no problems, mild problems, or severe problems in the "Usual activities" domain of EQ-5D-3 L will be assessed at baseline, year 1, and year 2 follow-up periods. EQ-5D-3 L is a generic tool for Patient Reported Outcomes (PRO) measurement that can assess patients' quality of life, irrespective of the disease and includes 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. There are 3 questions per domain where patients respond if they have no problems, mild, or severe problems.
Proportion of Patients With No Problems, Mild Problems, or Severe Problems in the "Pain / Discomfort" Domain of European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3 L) During the 2 Year Follow-up Period.	2 years of follow-up	Proportion of patients with no problems, mild problems, or severe problems in the "Pain / Discomfort" domain of EQ-5D-3 L will be assessed at baseline, year 1, and year 2 follow-up periods. EQ-5D-3 L is a generic tool for Patient Reported Outcomes (PRO) measurement that can assess patients' quality of life, irrespective of the disease and includes 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. There are 3 questions per domain where patients respond if they have no problems, mild, or severe problems.
Proportion of Patients With No Problems, Mild Problems, or Severe Problems in the "Anxiety / Depression" Domain of European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3 L) During the 2 Year Follow-up Period.	2 years of follow-up	Proportion of patients with no problems, mild problems, or severe problems in the "Anxiety / Depression" domain of EQ-5D-3 L will be assessed at baseline, year 1, and year 2 follow-up periods. EQ-5D-3 L is a generic tool for Patient Reported Outcomes (PRO) measurement that can assess patients' quality of life, irrespective of the disease and includes 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. There are 3 questions per domain where patients respond if they have no problems, mild, or severe problems.
Median T-score for "Social" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.	2 years of follow-up	Median T-score for "Social" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) at baseline, year 1 and year 2. PROMIS-29 (Version 2.0) is a generic health-related quality of life measure including 7 domains (anxiety, depression, fatigue, pain interference, sleep disturbance, and ability to participate in social roles and activities, and physical function).12 Each domain contains questions ranked using a 5-point Likert scale. PROMIS-29 domain scores are converted to T scores and have been standardized to a reference population (mean, 50; SD, 10). Clinically meaningful change is considered to be at least half the SD (5 points). Higher T-score indicates better outcome.