Clinical trial NCT03652181: CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness
Official title: CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: CCM
Cavernoma
Cerebral Cavernous Malformation
Cerebral Cavernous Malformations 1
Cerebral Cavernous Malformations 2
Cerebral Cavernous Malformations 3
Cavernous Angioma
Keywords: CCM (Cerebral Cavernous Malformations)
Dynamic Contrast Enhanced Quantitative Perfusion (DCEQP)
Quantitative Susceptibility Mapping (QSM)
Cerebral Cavernous Malformation
Cavernoma
Cavernous Angioma
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: Mayo Clinic
name: Johns Hopkins University
name: University of California, San Francisco
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: University of Utah
name: University of New Mexico
name: Barrow Neurological Institute
First posted: 2018-08-29
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Brain Cavernous Angiomas with Symptomatic Hemmhorage (CASH) that have occurred within the last year.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of Recurrent Symptomatic Hemorrhage During the Two Year Follow-up Period in Patients With CASH.
timeFrame: 2 year
Secondary outcomes:
measure: Percent Change in QSM Value (Lesional Iron Content)
timeFrame: 2 years of follow-up
measure: Percent Change in Contrast-enhanced Quantitative Perfusion (DCEQP) Value (Vascular Permeability)
timeFrame: 2 years of follow-up
measure: 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.
timeFrame: 2 years of follow-up
measure: Percentage of Patients With National Institutes of Health Stroke Scale (NIHSS) 0-4, 5-14 and 14+ During the 2 Year Follow-up Period.
timeFrame: 2 years of follow-up
measure: Median Score of European Quality of Life Visual Analogue Scale (EQ-VAS) During the 2 Year Follow-up Period.
timeFrame: 2 years of follow-up
measure: 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.
timeFrame: 2 years of follow-up
measure: 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.
timeFrame: 2 years of follow-up
measure: 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.
timeFrame: 2 years of follow-up
measure: 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.
timeFrame: 2 years of follow-up
measure: 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.
timeFrame: 2 years of follow-up
measure: Median T-score for "Anxiety" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
timeFrame: 2 years of follow-up
measure: Median T-score for "Depression" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
timeFrame: 2 years of follow-up
measure: Median T-score for "Fatigue" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
timeFrame: 2 years of follow-up
measure: Median T-score for "Pain" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
timeFrame: 2 years of follow-up
measure: Median T-score for "Sleep Disturbance" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
timeFrame: 2 years of follow-up
measure: Median T-score for "Social" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
timeFrame: 2 years of follow-up
measure: Median T-score for "Physical Function" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
timeFrame: 2 years of follow-up
Other outcomes:
Locations:
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
Study officials:
affiliation: University of Chicago
name: Issam A Awad, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Daniel Hanley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Kelly Flemming, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Helen Kim, MPH, PhD
role: PRINCIPAL_INVESTIGATOR
References: