CCM Blood Biomarker Validation Study

NCT05148663 | Terminated DMC FDA Drug

• 1 other identifier: E21010
• Study Type: observational
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Cerebral cavernous malformations (CCMs), one of the most common microvascular malformations in the capillary beds of the brain, are susceptible to hemorrhagic stroke. As an autosomal dominant disorder with incomplete penetrance, the majority of CCM gene mutation carriers are largely asymptomatic but when symptoms occur, the disease has typically reached the stage of focal hemorrhage with irreversible brain damage. Currently, the invasive neurosurgery removal of CCM lesions is the only treatment option, despite the recurrence of the symptoms after surgery. Therefore, there is a grave need for prognostic/monitoring biomarkers as risk predictors for stroke prevention. The objective of the proposal is to develop a set of blood prognostic/monitoring biomarkers as precise risk indicators for stroke prevention. In this project, the plan is to validate the novel serum biomarkers identified in Ccms animal models and human CCMs patients, and utilize these biomarkers with statistical algorithms for risk prediction of hemorrhagic CCMs. This proposal has been formulated based on recent findings of five serum etiological biomarkers associated with disruption of the Blood-Brain Barrier (BBB), the first step for hemorrhagic CCMs in Ccm mice models. This work will lay the groundwork for larger human trials for final validation and revolutionary potential clinical applications.

Conditions

Hemorrhagic Stroke, Intracerebral; Cerebral Cavernous Malformation

Outcome Measures

Primary Outcomes (1)

• Identification and validation of at least (>1) biomarker(s) with a significant p-value (p≤ 0.001) to correlate with the progression of hemorrhagic events in CCM patients using our optimized ELISAs.

  Confirmation of at least (\>1) biomarker(s) is essential for the feasibility assessment of this project after three years investigation and validation in the mid-sized cohorts (\~300 each cases/controls). Thus, to assess the consistency of the measurement between different CCM cohorts at the end of the 1st phase, the blinded test-retest reliability (r2) will be calculated with a relatively strong outcome range (\~0.65-0.70, p=0.005) on at least (\>1) positively/negatively correlated biomarker(s).

  the first two years

Study Arms (2)

blood drawing and hemorrhagic events in CCM patients

planned for three blood drawing before surgery

Diagnostic Test: CCM Hemorrhagic Panel

blood drawing for age/gender/ethnicity matched controls

Blood draw from Control patients with no inflammation

Diagnostic Test: CCM Hemorrhagic Panel

Interventions

CCM Hemorrhagic Panel DIAGNOSTIC_TEST

Biomarker

blood drawing and hemorrhagic events in CCM patients; blood drawing for age/gender/ethnicity matched controls

Eligibility Criteria

• Age: 10 Years - 78 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Mexican Hispanic population

You may qualify if:

• to 78 years of age.
• Medical history meets the criteria for the International Classification of Diseases diagnosis codes 10 (ICD-10) for cerebral cavernous malformations (CCMs) (Q28.3) or stroke/epilepsy.
• Has a family member whose medical history meets the criteria for the International Classification of Diseases diagnosis codes for cerebral cavernous malformations (CCMs) (Q28.3) or stroke/epilepsy.
• Has a relatively complete medical history that can be accurately confirmed by an interview or electronic and/or paper medical records.
• Hispanic and non-Hispanic Americans.

You may not qualify if:

• N/A

Sponsors & Collaborators

• Texas Tech University Health Sciences Center, El Paso: lead

Study Sites (1)

TTUHSC El Paso

El Paso, Texas, 79902, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Plasma can be used to isolated human DNA

MeSH Terms

Conditions

Hemorrhagic Stroke; Hemangioma, Cavernous, Central Nervous System

Condition Hierarchy (Ancestors)

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

Study Officials

• Jun Zhang

  TTUHSC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 27, 2021
• First Posted: December 8, 2021
• Study Start: January 1, 2021
• Primary Completion: August 29, 2023
• Study Completion: August 29, 2023
• Last Updated: September 1, 2023

Record last verified: 2023-08

Locations

US (1)