Carbon Dioxide Administration and Brain Waste Clearance

NCT07357090 | Recruiting

• 1 other identifier: 25-415
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The current study tests whether different exposures to carbon dioxide (CO2) can safely result in the increased movement of proteins from the brain into the blood. The investigators believe that this would be a proxy for the brain clearing waste products more effectively. The current study will use a counter-balanced design, in which individuals with and without a history of traumatic brain injury (TBI) will receive different levels of CO2 (targeted changes of approximately 5 or 10 mmHG in end-tidal CO2) approximately one week apart. The counter-balanced design means that each participant receives a single dose of CO2 at each visit, and different doses of CO2 at each visit. The order in which participants receive the dose is randomized, and the participant will not be informed of the dose.

Conditions

Traumatic Brain Injury; Aging Disorder; Magnetic Resonance Imaging (MRI)

Keywords

Traumatic Brain Injury; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (2)

• Cerebrovascular Reactivity (CVR), vascular-elicited bulk cerebral spinal fluid (VE-bCSF)

  Cerebrovascular reactivity (CVR) will be quantified using time-shifted end-tidal carbon dioxide (ETCO₂) regressors to model blood oxygen level-dependent (BOLD) changes using functional magnetic resonance imaging, capturing the temporally lagged positive relationship between ETCO₂ and the BOLD signal. Vascular enhanced changes in bulk CSF flow will be assessed by regressing band-pass filtered global grey matter signals and their derivatives on CSF bulk flow to capture the temporally lagged, negative relationship. Both of these measurements are in arbitrary units, and will be quantified by calculating percent signal change and statistical fit between regressors.

  2.5 hours post-intervention. Data will be reported at the conclusion of the study for all participants.

• Protein Efflux (Surrogate Measure of Brain Waste Clearance)

  Protein efflux from the brain to the blood will be measured using Quanterix platform, with primary proteins including neurofilament light chain, brain-derived tau and glial fibrillary acidic protein (units=picogram/milligram). For neurofilament light chain (NfL), the limit of detection (LOD) is 0.104 pg/mL, the range is 0.025-0.276 pg/mL, and the lower limit of quantification (LLOQ) is 0.241 pg/mL. For glial fibrillary acidic protein (GFAP), the LOD is 0.221 pg/mL, the range is 0.042-0.481 pg/mL, and the LLOQ is 0.467 pg/mL. For brain-derived tau (BD Tau), the LOD is 0.024 pg/mL, the range is 0.007-0.059 pg/mL, and the LLOQ is 0.053 pg/mL. All values are obtained from the Quanterix website datasheets.

  Blood will be drawn at baseline, immediately prior to hypercapnia, 45 minutes post-hypercapnia, 90 minutes post-hypercapnia and 150 minutes post-hypercapnia. Data will be reported at the conclusion of the study for all participants.

Secondary Outcomes (1)

• Symptoms

  After the first blood draw (i.e., blood collected at baseline), 10 and 20 minutes post-hypercapnia, as well as after blood collected 90-minutes post-hypercapnia. Data will be reported at the conclusion of the study for all participants.

Study Arms (2)

Individuals with TBI

EXPERIMENTAL

A counter-balanced, cross-over design (AB/BA), in which individuals with TBI (aged 18-82 years) may be dosed to achieve 5 or 10 mmHG changes in ETCO2 across multiple visits.

Other: Hypercapnia task performed during fMRI

Healthy Subjects

EXPERIMENTAL

A counter-balanced, cross-over design (AB/BA), in which individuals without a history of TBI (healthy subjects, aged 18-82 years) may be dosed to achieve 5 or 10 mmHG changes in ETCO2 across multiple visits.

Other: Hypercapnia task performed during fMRI

Interventions

Hypercapnia task performed during fMRI OTHER

This study looks at different levels of carbon dioxide (CO2) exposure (changes of approximately 5 or 10 mmHg) on the brain and proteins in blood, in response to a hypercapnia task while participants undergo MRI. This sequence will dynamically mix gases to target an increase of 5 or 10 mmHg in ETCO2 (increase of \~5-7% CO2 and equal decrease in nitrogen) while keeping O2 constant.

Healthy Subjects; Individuals with TBI

Eligibility Criteria

• Age: 18 Years - 82 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Andrew Mayer: lead

Study Sites (1)

The Mind Research Network

Albuquerque, New Mexico, 87106, United States

RECRUITING

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Andrew R Mayer, Phd

  Mind Research Network

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jody Roberts, MS

CONTACT

505-272-5028; jroberts@mrn.org

Andrew Mayer R The Mind Research Network, PhD

CONTACT

505-272-0769; amayer@mrn.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Translational Research

Study Record Dates

• First Submitted: January 9, 2026
• First Posted: January 21, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): February 1, 2032
• Last Updated: February 23, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)