NCT04467489

Brief Summary

The project aims to develop prognostic and diagnostic blood tests for symptomatic brain hemorrhage in patients diagnosed with cavernous angiomas, a critical clinical challenge in a disease affecting more than a million Americans. We further examine whether blood biomarkers can replace or enhance the accuracy of advanced imaging in association with lesional bleeding. The project tests a novel integrational approach of biomarker development in a mechanistically defined cerebrovascular disease, with a clinically relevant context of use.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,040

participants targeted

Target at P75+ for all trials

Timeline
1mo left

Started May 2020

Longer than P75 for all trials

Geographic Reach
1 country

4 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress98%
May 2020Jun 2026

Study Start

First participant enrolled

May 22, 2020

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

July 8, 2020

Completed
5 days until next milestone

First Posted

Study publicly available on registry

July 13, 2020

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2025

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2026

Expected
Last Updated

August 11, 2025

Status Verified

August 1, 2025

Enrollment Period

4.9 years

First QC Date

July 8, 2020

Last Update Submit

August 6, 2025

Conditions

Keywords

plasma biomarkerimaging biomarkermachine learning

Outcome Measures

Primary Outcomes (1)

  • Circulating Diagnostic and Prognostic Biomarkers of CASH

    To test whether individual and combined levels of candidate plasma proteins and miRNAs can be associated with diagnosis of CASH (cross sectional) and can predict/prognosticate future SH (longitudinal) in CAs

    5 years

Secondary Outcomes (2)

  • Correlation of Imaging and Plasma Biomarkers of CASH

    5 years

  • Confounders of CASH Biomarkers

    5 years

Study Arms (6)

CA (non-CASH)

Cavernous Angioma (CA) without symptomatic hemorrhage cases scheduled for evaluation by their neurology or neurosurgery teams in an inpatient or outpatient setting

Other: observational

CA (CASH)

Cavernous Angioma (CA) with Symptomatic Hemorrhage (SH) cases scheduled for evaluation by their neurology or neurosurgery teams in an inpatient or outpatient setting

Other: observational

Young with seizure

Young (\<30 years old) healthy control cohorts with seizures in the prior year

Other: observational

Young without seizure

Young (\<30 years old) healthy control cohorts without seizures in the prior year

Other: observational

Older with HMA

Older (\>50 years old) with hemorrhagic microangiopathy (HMA)

Other: observational

Older without HMA

Older (\>50 years old) without hemorrhagic microangiopathy (HMA)

Other: observational

Interventions

There is no intervention for any group in this observational study.

CA (CASH)CA (non-CASH)Older with HMAOlder without HMAYoung with seizureYoung without seizure

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

We propose to recruit human subjects at three sites, with the project approved and coordinated by the University of Chicago Medicine (UCM) central institutional review board (IRB) and endorsed by respective IRBs at the other two enrolling sites. The study involves no more than minimal risks, discussed herein. The enrolling sites include UCM where the project will be led and where the data coordinating center (DCC) is located and all plasma biomarker assays and statistical analyses are planned, the University of California at San Francisco (UCSF), and Mayo Clinic, Rochester, MN (Mayo). UCSF and Mayo are participants in imaging biomarker validations in longitudinal follow-up of cavernous angioma with symptomatic hemorrhage (CASH) subjects in the TR Project. We project enrolling 1,040 cases during 4 years to address hypotheses in 3 Specific Aims (40 cases enrolled in Specific Aim 2 are also included among the 800 subjects addressing hypotheses of Specific Aim 1).

You may qualify if:

  • Clinical diagnosis of CA
  • age 18 or older
  • solitary or multiple
  • familial or sporadic
  • with or without prior symptoms

You may not qualify if:

  • Prior excision of a solitary CA lesion
  • prior stereotactic radiosurgery or any brain irradiation
  • spinal cavernoma without brain lesion
  • other brain pathology unrelated to CA (demyelinating disease, brain tumor)
  • seizures or stroke unrelated to CA in the prior year
  • current pregnancy or within 6 months postpartum
  • reluctance to undergo venipuncture or donate blood specimen, or be called for clinical follow-up for up to one year
  • homeless or incarcerated persons, or other reason a subject will be unable/unlikely to be reached for follow-up
  • Aim 3:
  • \< 30 years of age
  • one or more seizures (with or without medical therapy) in the prior year
  • \> 50 years of age
  • having received an MRI of the brain with SWI (susceptibility weighted imaging) sequences for any indication in the year prior to enrollment
  • No HMA on brain MRI SWI sequences
  • \> 50 years of age
  • +22 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Barrow Neurological Institute at St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

University of California, San Francisco

San Francisco, California, 94117, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

  • Girard R, Li Y, Stadnik A, Shenkar R, Hobson N, Romanos S, Srinath A, Moore T, Lightle R, Shkoukani A, Akers A, Carroll T, Christoforidis GA, Koenig JI, Lee C, Piedad K, Greenberg SM, Kim H, Flemming KD, Ji Y, Awad IA. A Roadmap for Developing Plasma Diagnostic and Prognostic Biomarkers of Cerebral Cavernous Angioma With Symptomatic Hemorrhage (CASH). Neurosurgery. 2021 Feb 16;88(3):686-697. doi: 10.1093/neuros/nyaa478.

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma samples

MeSH Terms

Conditions

Hemangioma, Cavernous, Central Nervous SystemHemangioma, Cavernous

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

HemangiomaNeoplasms, Vascular TissueNeoplasms by Histologic TypeNeoplasmsCavernous Sinus SyndromesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesCentral Nervous System Vascular MalformationsNervous System MalformationsVascular MalformationsCardiovascular AbnormalitiesCardiovascular DiseasesHemostatic DisordersVascular DiseasesHemorrhagic DisordersHematologic DiseasesHemic and Lymphatic DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health CareOutcome and Process Assessment, Health CareQuality of Health CareHealth Services Administration

Study Officials

  • Issam Awad, MD

    University of Chicago

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Target Duration
1 Year
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 8, 2020

First Posted

July 13, 2020

Study Start

May 22, 2020

Primary Completion

April 30, 2025

Study Completion (Estimated)

June 30, 2026

Last Updated

August 11, 2025

Record last verified: 2025-08

Data Sharing

IPD Sharing
Will share

Within the first year, we will publish the protocol paper. At the end of the 5 year study, we will publish the data dictionary along with study findings. The expression profile data will be made publicly available no later than the date of initial publication or six months after the receipt of the final sequencing data, whichever comes first.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
The expression profile data will be made publicly available no later than the date of initial publication or six months after the receipt of the final sequencing data, whichever comes first.
Access Criteria
The expression profile data will be made publicly available.

Locations