Functional Magnetic Resonance Imaging (fMRI) Vascular Reactivity in Cerebral Cavernous Malformations (CCM)

The goal is to characterize vascular reactivity and cardiac pulsatility of normal appearing white matter in patients with CCM during hypercarbia/hypocarbia using quantitative real-time high-speed multi-echo fMRI to develop prognostic biomarkers for CCM formation

Study Overview

• Status: Terminated
• Conditions: Cerebral Cavernous Malformation
• Intervention / Treatment: Other: Hyperventilation and CO2 challenge

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Neurology Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

Patients already diagnosed with familial CCM. Suitable patients coming in the UNM CCM clinic will be contacted and requested to be a part of the study.

Description

Inclusion Criteria:

1. All familial CCM subjects presenting at UNMH who can consent to our study.
2. Adult Male/Female patients ages >18 years old

Exclusion Criteria:

1. Individuals ages <18 year
2. Subjects with a known fear of dyspnea or enclosed spaces will be excluded from this study as well as those with metal implants, COPD, heart conditions, and hypercapnia.
3. Subjects who have contraindications to MRI such as harboring incompatible ferromagnetic objects implanted in the body.
4. Pregnant women (screening for pregnancy will be performed by oral questionnaire. MRI is safe in pregnancy but the study will exclude pregnant subjects, as the effects of respiratory challenge cannot be predicted in such subjects. Since these effects are proportional to the stage of gestation, oral history will be sufficient to assure safety.)
5. Prisoners.
6. People unable to consent.
7. People unable to participate due to prior neurological deficits.
8. Subjects with underlying pre-existing pulmonary illness; such as asthma, COPD, pulmonary hypertension, will be excluded.
9. Cognitively impaired and/or participants not able to speak English language will not be included in the study (This pilot study involves performing motor and verbal tasks while in the MRI, in addition to undergoing a respiratory challenge, that requires understanding instructions clearly. We do not have current capabilities to include a translator who would be available at all stages of the study to include subjects who do not speak English.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hypercarbia/Hypocarbia/resting state during fMRI; During real time fMRI, all subjects will completed breathing tasks though a mask that supplies gas mixtures using the RespirAct™ Gas Control System (Thornhill Medical). The RespirAct™ is a computer-controlled gas blender providing carbon dioxide (CO2), oxygen (O2) and nitrogen for a subject to inhale while breathing for the purpose of controlling the concentrations of the respective blood gases. For hypocarbia, subjects will be instructed to pace their breathing to 16- 20 breaths-per-minute to achieve a stable target end-tidal CO2 between 30 and 40 mm Hg. Hypercarbia will be induced by increasing CO2 concentration and flow rate of the gas mixture until a desired ETCO2 level between 40 and 50 mm Hg has been reached. There will also be a 10 minutes rest period during which respiratory rate and heart rate will be monitored continuously.

Other: Hyperventilation and CO2 challenge; Subjects will also be asked to complete hyperventilation and CO2 breathing tasks based on instruction from the study investigators as described in study arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic Response	Primary end point of the study is to measure the amplitude and frequency response of hemodynamic response function during hypercarbia/hypocarbia using task-based functional MRI	12 Months
Resting state connectivity	To measure the strength of resting-state connectivity during hypercarbia/hypocarbia using high-speed multi-echo resting-state functional MRI.	12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Pulsatility	Measure the amplitude and frequency spectrum of the cardiac pulsatility during hypercarbia/hypocarbia in functional MRI time series that are acquired using high-speed multi-echo functional MRI	12 Months
First Harmonic	To measure the amplitude ratio of the first harmonic of the cardiac pulsatility relative to the cardiac base frequency in these data, which is a biomarker of vascular compliance.speed multi echo fMRI.	12 Months

Collaborators and Investigators

• Sponsor: University of New Mexico
• Collaborators: University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2023
• Primary Completion (Actual): July 17, 2024
• Study Completion (Actual): July 17, 2024

Study Registration Dates

• First Submitted: March 9, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): March 28, 2022

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cavernous Sinus Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Cardiovascular Abnormalities; Hemostatic Disorders; Hemorrhagic Disorders; Neoplasms, Vascular Tissue; Nervous System Malformations; Vascular Malformations; Hemangioma; Central Nervous System Vascular Malformations; Hemangioma, Cavernous; Congenital Abnormalities; Hemangioma, Cavernous, Central Nervous System
• Other Study ID Numbers: 21-136

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There would not be any plans in place to share IPD. All data will be de-identified and not linked to any individual participant.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No