CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness

Cerebral Cavernous Malformation Clinical Trial

Official title:

CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03652181
• Other study ID #: U01NS104157
• Secondary ID: U01NS104157
• Status: Completed
• Start date: August 20, 2018
• Est. completion date: November 3, 2022

Study information

• Verified date: March 2024
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 181
• Est. completion date: November 3, 2022
• Est. primary completion date: November 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

1. 18 years of age and older

2. Diagnosed with a brain CA (single or multiple)

3. Had a SH within the past year (with demonstrated new lesional bleeding or hemorrhagic growth on diagnostic studies AND attributable new symptoms)

4. Subject is able to provide informed consent

Exclusion Criteria

1. Spinal CA as source of SH

2. Prior brain irradiation

3. Cases where verification of SH with clinical and imaging review cannot be accomplished

4. Prior or planned treatment of the symptomatic lesion (after neurosurgical consultation)

To be eligible for Aims 2 and 3, CASH cases enrolled in Aim 1 will be further excluded from follow-up and baseline validation (FUBV) for the following reasons:

1. Contraindication for administration of contrast agent or otherwise unwilling or unable to undergo research MRI studies

2. Pregnant or breastfeeding women

3. Homeless or incarcerated persons, or other reason a subject will be unable/unlikely to return for follow-up visits

Related Conditions & MeSH terms

• Cavernoma
• Cavernous Angioma
• CCM
• Cerebral Cavernous Malformation
• Cerebral Cavernous Malformations 1
• Cerebral Cavernous Malformations 2
• Cerebral Cavernous Malformations 3
• Congenital Abnormalities
• Hemangioma
• Hemorrhage

Locations

Country	Name	City	State
United States	The University of Chicago Medical Center	Chicago	Illinois

Sponsors (8)

Lead Sponsor	Collaborator
University of Chicago	Barrow Neurological Institute, Johns Hopkins University, Mayo Clinic, National Institute of Neurological Disorders and Stroke (NINDS), University of California, San Francisco, University of New Mexico, University of Utah

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of recurrent symptomatic hemorrhage during the two year follow-up period in patients with CASH.	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 bleeds from baseline to year 1, baseline to year 2, and year 1 to year 2 year follow-up.	2 year
Secondary	Mean Quantitative susceptibility mapping (QSM) change during the 2 year follow-up period.	Change in QSM value will be assessed from baseline to year 1 and year 1 to year 2 follow-up MRIs.	2 years of follow-up
Secondary	Mean dynamic contrast-enhanced quantitative perfusion (DCEQP) change during the 2 year follow-up period.	Change in DCEQP value from the MRIs will be assessed from baseline to year 1 and year 1 to year 2 of follow-up	2 years of follow-up
Secondary	Change in the the proportion of patients with mRS score 0 to 1 during the 2 year follow-up period.	Change in the proportion of patients with mRS score 0 to will be assessed 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.	2 years of follow-up
Secondary	Change in the median National Institutes of Health Stroke Scale (NIHSS) during the 2 year follow-up period.	Change in median NIHSS value will be assessed 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.	2 years of follow-up
Secondary	Change in the median score of European Quality of Life Visual Analogue Scale (EQ-VAS) during the 2 year follow-up period.	Change in the median score of EQ-VAS will be assessed from baseline to year 1 and year 1 to year 2 follow-up periods.; 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.	2 years of follow-up
Secondary	Change in proportion of patients with no problems, mild, 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.	Change in proportion of patients with no problems, mild, or severe problems in the "Mobility" domain of EQ-5D-3 L will be assessed from baseline to year 1 and year 1 to 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.	2 years of follow-up
Secondary	Change in proportion of patients with no problems, mild, 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.	Change in proportion of patients with no problems, mild, or severe problems in the "Self-care" domain of EQ-5D-3 L will be assessed from baseline to year 1 and year 1 to 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.	2 years of follow-up
Secondary	Change in proportion of patients with no problems, mild, 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.	Change in proportion of patients with no problems, mild, or severe problems in the "Usual activities" domain of EQ-5D-3 L will be assessed from baseline to year 1 and year 1 to 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.	2 years of follow-up
Secondary	Change in proportion of patients with no problems, mild, 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.	Change in proportion of patients with no problems, mild, or severe problems in the "Pain / Discomfort" domain of EQ-5D-3 L will be assessed from baseline to year 1 and year 1 to 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.	2 years of follow-up
Secondary	Change in proportion of patients with no problems, mild, 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.	Change in proportion of patients with no problems, mild, or severe problems in the "Anxiety / Depression" domain of EQ-5D-3 L will be assessed from baseline to year 1 and year 1 to 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.	2 years of follow-up
Secondary	Change in the median T-score for "Anxiety" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) during the 2 year follow-up period.	Change in the median T-score for "Anxiety" domain of PROMIS-29 will be assessed from baseline to year 1 and year 1 to year 2 follow-up periods.; 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).	2 years of follow-up
Secondary	Change in the median T-score for "Depression" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) during the 2 year follow-up period.	Change in the median T-score for "Depression" domain of PROMIS-29 will be assessed from baseline to year 1 and year 1 to year 2 follow-up periods.; 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).	2 years of follow-up
Secondary	Change in the median T-score for "Fatigue" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) during the 2 year follow-up period.	Change in the median T-score for "Fatigue" domain of PROMIS-29 will be assessed from baseline to year 1 and year 1 to year 2 follow-up periods.; 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).	2 years of follow-up
Secondary	Change in the median T-score for "Pain" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) during the 2 year follow-up period.	Change in the median T-score for "Pain" domain of PROMIS-29 will be assessed from baseline to year 1 and year 1 to year 2 follow-up periods.; 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).	2 years of follow-up
Secondary	Change in the median T-score for "Sleep Disturbance" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) during the 2 year follow-up period.	Change in the median T-score for "Sleep Disturbance" domain of PROMIS-29 will be assessed from baseline to year 1 and year 1 to year 2 follow-up periods.; 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).	2 years of follow-up
Secondary	Change in the median T-score for "Social" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) during the 2 year follow-up period.	Change in the median T-score for "Social" domain of PROMIS-29 will be assessed from baseline to year 1 and year 1 to year 2 follow-up periods.; 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).	2 years of follow-up
Secondary	Change in the median T-score for "Physical Function" domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) during the 2 year follow-up period.	Change in the median T-score for "Physical Function" domain of PROMIS-29 will be assessed from baseline to year 1 and year 1 to year 2 follow-up periods.; 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).	2 years of follow-up