CCMNCT03652181
CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness
An observational study of CCM and Cavernoma, run by University of Chicago at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CCM, Cavernoma, Cerebral Cavernous Malformation
- How many people
- 123 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Aug 2018to 3 Nov 2022
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with Brain Cavernous Angiomas with Symptomatic Hemmhorage (CASH) that have occurred within the last year.
Who may be able to join
- 18 years of age and older
- Diagnosed with a brain CA (single or multiple)
- Had a SH within the past year (with demonstrated new lesional bleeding or hemorrhagic growth on diagnostic studies AND attributable new symptoms)
- Subject is able to provide informed consent
Who cannot join
- Spinal CA as source of SH
- Prior brain irradiation
- Cases where verification of SH with clinical and imaging review cannot be accomplished
- 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:
- Contraindication for administration of contrast agent or otherwise unwilling or unable to undergo research MRI studies
- Pregnant or breastfeeding women
- Homeless or incarcerated persons, or other reason a subject will be unable/unlikely to return for follow-up visits
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Chicago Medical Center
Chicago, Illinois, 60637
About this study
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.
Read the 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.
- Conditions
- CCM, Cavernoma, Cerebral Cavernous Malformation, Cerebral Cavernous Malformations 1, Cerebral Cavernous Malformations 2, Cerebral Cavernous Malformations 3
- Keywords
- CCM (Cerebral Cavernous Malformations), Dynamic Contrast Enhanced Quantitative Perfusion (DCEQP), Quantitative Susceptibility Mapping (QSM), Cerebral Cavernous Malformation, Cavernoma, Cavernous Angioma
- Medical subject headings
- Hemangioma, Capillary, Hemangioma, Cavernous, Central Nervous System, Cerebral Cavernous Malformations 2, Cerebral Cavernous Malformations 3, Hemangioma, Cavernous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| CASH (Cavernous Angiomas with Symptomatic Hemorrhage) | The adjudicated definition of CASH (Cavernous Angiomas with Symptomatic Hemorrhage) requires diagnostic evidence of new lesional bleeding or hemorrhagic growth, in association with directly attributable symptoms. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 new symptomatic hemorrhage from baseline to year 1 and year 1 to year 2 follow-up.
Measured: 2 year
Secondary outcomes (17)
Percent Change in QSM Value (Lesional Iron Content)
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
Measured: 2 years of follow-up
Percent Change in Contrast-enhanced Quantitative Perfusion (DCEQP) Value (Vascular Permeability)
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
Measured: 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 During the 2 Year Follow-up Period.
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.
Measured: 2 years of follow-up
Percentage of Patients With National Institutes of Health Stroke Scale (NIHSS) 0-4, 5-14 and 14+ During the 2 Year Follow-up Period.
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.
Measured: 2 years of follow-up
Median Score of European Quality of Life Visual Analogue Scale (EQ-VAS) During the 2 Year Follow-up Period.
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.
Measured: 2 years of follow-up
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.
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.
Measured: 2 years of follow-up
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.
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.
Measured: 2 years of follow-up
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.
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.
Measured: 2 years of follow-up
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.
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.
Measured: 2 years of follow-up
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.
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.
Measured: 2 years of follow-up
Median T-score for "Anxiety" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
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.
Measured: 2 years of follow-up
Median T-score for "Depression" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
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.
Measured: 2 years of follow-up
Median T-score for "Fatigue" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
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.
Measured: 2 years of follow-up
Median T-score for "Pain" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
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.
Measured: 2 years of follow-up
Median T-score for "Sleep Disturbance" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
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.
Measured: 2 years of follow-up
Median T-score for "Social" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
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.
Measured: 2 years of follow-up
Median T-score for "Physical Function" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
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.
Measured: 2 years of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2018
- Study start20 Aug 2018
- Primary completion3 Nov 2022
- Study completion3 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for CCMStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- Mayo Clinic, Johns Hopkins University, University of California, San Francisco, National Institute of Neurological Disorders and Stroke (NINDS), University of Utah, University of New Mexico, Barrow Neurological Institute
- Responsible party
- Sponsor
- Investigators
- Issam A Awad, MD, Principal investigator, University of ChicagoDaniel Hanley, MD, Principal investigator, Johns Hopkins UniversityKelly Flemming, MD, Principal investigator, Mayo ClinicHelen Kim, MPH, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03652181
- Sponsor's protocol ID
- U01NS104157
- Other IDs
- U01NS104157
- Status last verified
- Jun 2024
- First submitted
- 18 Jul 2018
- Last updated
- 27 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study Protocol has been published in Neurosurgery
Publications
Kinkade S, Li H, Hage S, Koskimaki J, Stadnik A, Lee J, Shenkar R, Papaioannou J, Flemming KD, Kim H, Torbey M, Huang J, Carroll TJ, Girard R, Giger ML, Awad IA. Identifying features of prior hemorrhage in cerebral cavernous malformations on quantitative susceptibility maps: a machine learning pilot study. J Neurosurg. 2025 Jul 4;143(6):1567-1574. doi: 10.3171/2025.3.JNS243051. Print 2025 Dec 1.
PubMed 40614265Flemming KD, Kim H, Hage S, Mandrekar J, Kinkade S, Girard R, Torbey M, Huang J, Huston J 3rd, Shu Y, Lanzino G, Selwyn R, Hart B, Mabray M, Feghali J, Sair HI, Narvid J, Lupo JM, Lee J, Stadnik A, Alcazar-Felix RJ, Shenkar R, Lane K, McBee N, Treine K, Ostapkovich N, Wang Y, Thompson R, Koenig JI, Carroll T, Hanley D, Awad I. Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part I: Event Rates and Clinical Outcome. Stroke. 2024 Jan;55(1):22-30. doi: 10.1161/STROKEAHA.123.044068. Epub 2023 Dec 22.
PubMed 38134268Hage S, Kinkade S, Girard R, Flemming KD, Kim H, Torbey MT, Huang J, Huston J 3rd, Shu Y, Selwyn RG, Hart BL, Mabray MC, Feghali J, Sair HI, Narvid J, Lupo JM, Lee J, Stadnik A, Alcazar-Felix RJ, Shenkar R, Hobson N, DeBiasse D, Lane K, McBee NA, Treine K, Ostapkovich N, Wang Y, Thompson RE, Koenig JI, Carroll T, Hanley DF Jr, Awad IA. Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part II: Biomarkers and Trial Modeling. Stroke. 2024 Jan;55(1):31-39. doi: 10.1161/STROKEAHA.123.044083. Epub 2023 Dec 22.
PubMed 38134265Hage S, Kinkade S, Girard R, Flemming KD, Kim H, Torbey MT, Huang J, Huston J, Shu Y, Selwyn RG, Hart BL, Mabray MC, Feghali J, Sair HI, Narvid J, Lupo JM, Lee J, Stadnik A, Alcazar R, Shenkar R, Hobson N, DeBiasse D, Lane K, McBee N, Treine K, Ostapkovich N, Wang Y, Thompson RE, Mendoza-Puccini C, Koenig J, Carroll T, Hanley DF, Awad IA. Cavernous Angioma Symptomatic Hemorrhage (CASH) Trial Readiness II: Imaging Biomarkers and Trial Modeling. medRxiv [Preprint]. 2023 Jun 5:2023.06.01.23290854. doi: 10.1101/2023.06.01.23290854.
PubMed 37333396
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness
- ClinicalTrials.gov ID
- NCT03652181
- Acronym / sponsor ID
- U01NS104157
- Conditions
- CCM, Cavernoma, Cerebral Cavernous Malformation, Cerebral Cavernous Malformations 1, Cerebral Cavernous Malformations 2, Cerebral Cavernous Malformations 3
- Keywords
- CCM (Cerebral Cavernous Malformations), Dynamic Contrast Enhanced Quantitative Perfusion (DCEQP), Quantitative Susceptibility Mapping (QSM), Cerebral Cavernous Malformation, Cavernoma, Cavernous Angioma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Collaborators
- Mayo Clinic, Johns Hopkins University, University of California, San Francisco, National Institute of Neurological Disorders and Stroke (NINDS), University of Utah, University of New Mexico, Barrow Neurological Institute
- Study start
- 20 Aug 2018 (actual)
- Primary completion
- 3 Nov 2022 (actual)
- Study completion
- 3 Nov 2022 (actual)
- First posted
- 29 Aug 2018 (actual)
- Results
- Posted 27 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CASH (Cavernous Angiomas with Symptomatic Hemorrhage) | – | –The adjudicated definition of CASH (Cavernous Angiomas with Symptomatic Hemorrhage) requires diagnostic evidence of new lesional bleeding or hemorrhagic growth, in association with directly attributable symptoms. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with Brain Cavernous Angiomas with Symptomatic Hemmhorage (CASH) that have occurred within the last year.
Key inclusion criteria (4 listed)
- 18 years of age and older
- Diagnosed with a brain CA (single or multiple)
- Had a SH within the past year (with demonstrated new lesional bleeding or hemorrhagic growth on diagnostic studies AND attributable new symptoms)
- Subject is able to provide informed consent
Key exclusion criteria (8 listed)
- Spinal CA as source of SH
- Prior brain irradiation
- Cases where verification of SH with clinical and imaging review cannot be accomplished
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Rate of Recurrent Symptomatic Hemorrhage During the Two Year Follow-up Period in Patients With CASH.
Time frame: 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.
17 secondary outcomes
Percent Change in QSM Value (Lesional Iron Content)
Time frame: 2 years of follow-up
Percent Change in Contrast-enhanced Quantitative Perfusion (DCEQP) Value (Vascular Permeability)
Time frame: 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 During the 2 Year Follow-up Period.
Time frame: 2 years of follow-up
Percentage of Patients With National Institutes of Health Stroke Scale (NIHSS) 0-4, 5-14 and 14+ During the 2 Year Follow-up Period.
Time frame: 2 years of follow-up
Median Score of European Quality of Life Visual Analogue Scale (EQ-VAS) During the 2 Year Follow-up Period.
Time frame: 2 years of follow-up
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.
Time frame: 2 years of follow-up
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.
Time frame: 2 years of follow-up
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.
Time frame: 2 years of follow-up
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.
Time frame: 2 years of follow-up
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.
Time frame: 2 years of follow-up
Median T-score for "Anxiety" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
Time frame: 2 years of follow-up
Median T-score for "Depression" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
Time frame: 2 years of follow-up
Median T-score for "Fatigue" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
Time frame: 2 years of follow-up
Median T-score for "Pain" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
Time frame: 2 years of follow-up
Median T-score for "Sleep Disturbance" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
Time frame: 2 years of follow-up
Median T-score for "Social" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
Time frame: 2 years of follow-up
Median T-score for "Physical Function" Domain of Patient-Reported Outcome Measurement Information System (PROMIS-29) During the 2 Year Follow-up Period.
Time frame: 2 years of follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40614265Kinkade S, Li H, Hage S, Koskimaki J, Stadnik A, Lee J, Shenkar R, Papaioannou J, Flemming KD, Kim H, Torbey M, Huang J, Carroll TJ, Girard R, Giger ML, Awad IA. Identifying features of prior hemorrhage in cerebral cavernous malformations on quantitative susceptibility maps: a machine learning pilot study. J Neurosurg. 2025 Jul 4;143(6):1567-1574. doi: 10.3171/2025.3.JNS243051. Print 2025 Dec 1.
- Derived from this study: PubMed 38134268Flemming KD, Kim H, Hage S, Mandrekar J, Kinkade S, Girard R, Torbey M, Huang J, Huston J 3rd, Shu Y, Lanzino G, Selwyn R, Hart B, Mabray M, Feghali J, Sair HI, Narvid J, Lupo JM, Lee J, Stadnik A, Alcazar-Felix RJ, Shenkar R, Lane K, McBee N, Treine K, Ostapkovich N, Wang Y, Thompson R, Koenig JI, Carroll T, Hanley D, Awad I. Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part I: Event Rates and Clinical Outcome. Stroke. 2024 Jan;55(1):22-30. doi: 10.1161/STROKEAHA.123.044068. Epub 2023 Dec 22.
- Derived from this study: PubMed 38134265Hage S, Kinkade S, Girard R, Flemming KD, Kim H, Torbey MT, Huang J, Huston J 3rd, Shu Y, Selwyn RG, Hart BL, Mabray MC, Feghali J, Sair HI, Narvid J, Lupo JM, Lee J, Stadnik A, Alcazar-Felix RJ, Shenkar R, Hobson N, DeBiasse D, Lane K, McBee NA, Treine K, Ostapkovich N, Wang Y, Thompson RE, Koenig JI, Carroll T, Hanley DF Jr, Awad IA. Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part II: Biomarkers and Trial Modeling. Stroke. 2024 Jan;55(1):31-39. doi: 10.1161/STROKEAHA.123.044083. Epub 2023 Dec 22.
- Derived from this study: PubMed 37333396Hage S, Kinkade S, Girard R, Flemming KD, Kim H, Torbey MT, Huang J, Huston J, Shu Y, Selwyn RG, Hart BL, Mabray MC, Feghali J, Sair HI, Narvid J, Lupo JM, Lee J, Stadnik A, Alcazar R, Shenkar R, Hobson N, DeBiasse D, Lane K, McBee N, Treine K, Ostapkovich N, Wang Y, Thompson RE, Mendoza-Puccini C, Koenig J, Carroll T, Hanley DF, Awad IA. Cavernous Angioma Symptomatic Hemorrhage (CASH) Trial Readiness II: Imaging Biomarkers and Trial Modeling. medRxiv [Preprint]. 2023 Jun 5:2023.06.01.23290854. doi: 10.1101/2023.06.01.23290854.
- Individual participant dataSharing planned: Yes. Study Protocol has been published in Neurosurgery
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Issam A Awad, MD principal investigator
University of Chicago
Daniel Hanley, MD principal investigator
Johns Hopkins University
Kelly Flemming, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of CCM and Cavernoma, run by University of Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Recurrent Symptomatic Hemorrhage During the Two Year Follow-up Period in Patients With CASH. (time frame: 2 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03652181, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2024.