CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness

NCT03652181 | Completed Results DMC

• 1 other identifier: U01NS104157
• Study Type: observational
• Target: 123
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  2 year

Secondary Outcomes (17)

• Percent Change in QSM Value (Lesional Iron Content)

  2 years of follow-up

• Percent Change in Contrast-enhanced Quantitative Perfusion (DCEQP) Value (Vascular Permeability)

  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.

  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.

  2 years of follow-up

• Median Score of European Quality of Life Visual Analogue Scale (EQ-VAS) During the 2 Year Follow-up Period.

  2 years of follow-up

Study Arms (1)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with Brain Cavernous Angiomas with Symptomatic Hemmhorage (CASH) that have occurred within the last year.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Chicago: lead
• Mayo Clinic: collaborator
• Johns Hopkins University: collaborator
• University of California, San Francisco: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• University of Utah: collaborator
• University of New Mexico: collaborator
• Barrow Neurological Institute: collaborator

Study Sites (1)

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Related Publications (4)

• 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.

  PMID: 40614265 DERIVED

• Flemming 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.

  PMID: 38134268 DERIVED

• Hage 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.

  PMID: 38134265 DERIVED

• Hage 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.

  PMID: 37333396 DERIVED

MeSH Terms

Conditions

Hemangioma, Capillary; Hemangioma, Cavernous, Central Nervous System; Cerebral Cavernous Malformations 2; Cerebral Cavernous Malformations 3; Hemangioma, Cavernous

Condition Hierarchy (Ancestors)

Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms; Cavernous Sinus Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Central Nervous System Vascular Malformations; Nervous System Malformations; Vascular Malformations; Cardiovascular Abnormalities; Cardiovascular Diseases; Hemostatic Disorders; Vascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Agnieszka Stadnik
• Organization: University of Chicago, Medicine and Biological Sciences Division

astadnik@bsd.uchicago.edu

(773) 702-8996

Study Officials

• Issam A Awad, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

• Daniel Hanley, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Kelly Flemming, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Helen Kim, MPH, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2018
• First Posted: August 29, 2018
• Study Start: August 20, 2018
• Primary Completion: November 3, 2022
• Study Completion: November 3, 2022
• Last Updated: June 27, 2024
• Results First Posted: June 27, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Protocol paper was published November 2018 in Neurosurgery
• Access Criteria: can be accessed through Neurosurgery or Pubmed. Primary study contacts can also provide a copy upon request.

Locations

US (1)