Using carbon dioxide to promote brain waste clearance
Mechanisms Underlying Carbon Dioxide Induced Protein Efflux in Health and Traumatic Brain Injury
This trial will test whether brief, controlled increases in inhaled carbon dioxide help move proteins from the brain into the blood in adults with and without a history of traumatic brain injury.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 200 (estimated) |
| Ages | 18 Years to 82 Years |
| Sex | All |
| Sponsor | The Mind Research Network Academic / other |
| Locations | 1 site (Albuquerque, New Mexico) |
| Trial ID | NCT07357090 on ClinicalTrials.gov |
What this trial studies
Adults aged 18–82 with and without chronic traumatic brain injury will undergo two counter-balanced sessions in which breathing gases are adjusted to raise end-tidal CO2 by about 5 or 10 mmHg while they have an fMRI. Each participant receives both CO2 levels in randomized order roughly one week apart, with participants blinded to the dose. High-sensitivity proteomic assays will measure baseline and post-CO2 protein levels in blood as a surrogate for brain waste efflux, and cerebrovascular measures from MRI will probe mechanisms. The study tests dose-dependence of CO2-induced protein efflux and how individual cerebrovascular function or brain atrophy modify the response.
Who should consider this trial
Good fit: Ideal candidates are adults 18–82 who can give informed consent, are eligible for MRI, and either have a confirmed history of adult-onset traumatic brain injury or are healthy controls without prior TBI.
Not a fit: Patients with diagnosed Alzheimer’s disease or other dementias or mild cognitive impairment, pre-existing autism spectrum disorder or intellectual disability, serious neurological or psychiatric disorders prior to TBI, pregnancy, MRI contraindications, incarceration, or those outside the 18–82 age range are unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, the approach could point to a noninvasive way to boost brain waste clearance and identify biomarkers or treatment pathways for TBI-related and age-related brain problems.
How similar studies have performed: Animal studies and human sleep-related research support glymphatic CSF flow and waste clearance, but using prescribed CO2 to drive protein efflux in humans is relatively novel with limited direct human evidence.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion criteria for TBI cohort: 1) Able to give valid informed consent, 2) 18-82 years old, 3) history of TBI of any severity level (mild, moderate or severe) that was sustained in adulthood (age 18 and older), which will be confirmed using a semi-structured identification method (includes asking about loss of consciousness, posttraumatic amnesia, and feeling dazed/confused). Inclusion criteria for Healthy Subjects cohort: 1) Able to give valid informed consent and 2) 18-82 years old years old. Exclusion criteria for TBI cohort: 1) contraindications to MRI scanning including pregnancy or claustrophobia, 2) unable to give valid informed consent, incarcerated, 3) diagnosed with Alzheimer's, ADRD or mild cognitive impairment, 4) pre-existing history of autism spectrum disorders, intellectual disability, serious neurological (e.g., epilepsy, tumors, other conditions requiring neurosurgery) or psychiatric disorders (requiring hospitalization) prior to TBI onset, 5) current or previous diagnosis of a psychosis spectrum disorder or bipolar disorder, 6) respiratory diseases or pulmonary conditions that may increase the risk of study procedures (e.g., severe asthma, chronic obstructive pulmonary disease or other significant respiratory disorders), 7) a history of cardiac arrythmias 8) history of a current substance use disorder, 9) non-English fluency (based on screener), 10) Weigh under 110 pounds for blood draw. Exclusion criteria for Healthy Subjects cohort: 1) contraindications to MRI scanning including pregnancy or claustrophobia, 2) unable to give valid informed consent, incarcerated, 3) diagnosed with Alzheimer's, ADRD or mild cognitive impairment, 4) history of developmental, neurological, or psychiatric disorders requiring hospitalization, 5) regular use of any substance in the past six months (i.e., no current use confirmed with urine screening), 6) previous head injury with greater than 30 minutes loss of consciousness, 7) respiratory diseases or pulmonary conditions that may increase the risk of study procedures (e.g., severe asthma, chronic obstructive pulmonary disease or other significant respiratory disorders), 8) a history of cardiac arrythmias, 9) non-English fluency (based on screener), 10) Weigh under 110 pounds for blood draw.
Where this trial is running
Albuquerque, New Mexico
- The Mind Research Network — Albuquerque, New Mexico, United States (Recruiting)
Study contacts
- Principal investigator: Andrew R Mayer, Phd — Mind Research Network
- Study coordinator: Jody Roberts, MS
- Email: jroberts@mrn.org
- Phone: 505-272-5028
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.