Carbon Dioxide Challenge for Brain Blood Flow

Enrolling by invitation at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must not be taking: Stimulants, Antidepressants, Vasodilators

Disqualifiers: Lung disease, Heart failure, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how blood flow and metabolism in the brain differ between healthy adults and those with certain brain vessel issues. Participants will breathe in controlled levels of carbon dioxide (CO2, also known as carbonic anhydride) to observe how their brain's blood vessels react. MRI scans capture this process. The study suits adults who don’t take stimulants, aren’t on daily headache medication, and haven’t seen a psychiatrist for treatment. Participants should be free of conditions like seizures or severe heart or lung disease.

As an unphased trial, this study offers participants a chance to contribute to foundational research that could improve understanding of brain health.

Will I have to stop taking my current medications?

The trial requires that you are not on stimulant medications, anti-depressant medications, or vasodilatory medications like sildenafil or verapamil. If you are taking these, you would need to stop before participating.

What prior data suggests that this device is safe for measuring brain blood flow?

Research has shown that using carbon dioxide (CO2) in studies of blood flow in the brain is generally safe. Studies have not reported any negative effects in animals or humans. Researchers use CO2 because it can widen blood vessels in the brain, increasing blood flow without increasing brain activity. This helps assess how well blood vessels can expand and deliver oxygen.

Overall, evidence suggests that CO2 is well-tolerated in these tests. Notably, the studies found no harmful effects on participants, making it a safe option for examining brain blood flow. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using carbon dioxide to study brain blood flow because it offers a unique way to understand how blood vessels in the brain adapt to changes. Unlike typical treatments that directly target vascular issues with medications or surgery, this method involves inhaling carbon dioxide to safely and non-invasively alter blood flow. This could help identify early signs of vascular problems in the brain, potentially leading to better diagnostic tools and preventative strategies. The ability to observe real-time changes in brain circulation makes this approach particularly promising for advancing our understanding of cerebrovascular health.

What evidence suggests that this device is effective for studying brain blood flow?

Research has shown that carbon dioxide (CO2) greatly impacts blood flow in the brain. Studies have found that inhaling CO2 causes blood vessels in the brain to widen, increasing blood flow without boosting brain activity. As a result, the brain receives more oxygen-rich blood. One study discovered that CO2 uses the same pathways that link nerve activity to blood flow, aiding this process. This trial will compare the effects of CO2 on brain blood flow in healthy adults and those diagnosed with vascular pathology of the brain. These findings suggest that CO2 could help understand and assess how brain blood vessels react to changes, especially in individuals with brain blood vessel issues. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy adults over 18 or those with brain vascular issues, without a history of seizures, psychiatric conditions, or on certain medications like vasodilators. Participants must be able to undergo an MRI without sedation and not require daily headache prevention meds.

Inclusion Criteria

I sometimes have headaches but don't take daily medication for them.

I have not seen a psychiatrist nor taken antidepressants.

I am not taking any medication that widens my blood vessels.

Exclusion Criteria

I am unable to undergo rehabilitation therapy.

I cannot have an MRI due to a health condition, device, or metal in my body.

I have severe heart failure or lung disease with a resting breathing rate over 15 breaths per minute.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Respiratory Challenge

Participants undergo MRI imaging while breathing controlled air with varying CO2 levels to study brain blood flow and metabolism

1-2 weeks

1-2 visits (in-person)

Follow-up

Participants are monitored for any changes in brain blood flow and metabolism after the respiratory challenge

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carbon Dioxide

Trial Overview The study tests how the brain's blood vessels respond to different levels of carbon dioxide and oxygen using a special mask during MRI imaging. It aims to understand blood flow and metabolism changes in normal individuals versus patients with disease.

How Is the Trial Designed?

Group I: Healthy Adults Active Control 1 Intervention

Group II: Adults diagnosed with vascular pathology of the brain Active Control 1 Intervention

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

Acetazolamide, a carbonic anhydrase inhibitor, significantly increased cerebral blood flow (CBF) by up to 75% within 25 minutes of intravenous injection in healthy humans, indicating its rapid vasodilatory effects on cerebral arterioles.

The drug did not affect ventilation or blood gas levels, suggesting that its vasodilatory action is independent of its role as a carbonic anhydrase inhibitor and occurs over a wide range of carbon dioxide levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of acetazolamide on cerebral blood flow in man. Hauge, A., Nicolaysen, G., Thoresen, M.[2013]

In a study involving 14 dogs, the rapid injection of large quantities of carbon dioxide (CO2) into the arteries resulted in effective filling of the arteries and intracranial veins, as confirmed by advanced imaging techniques.

No adverse effects were observed during or after the procedure, with the dogs remaining neurologically normal for up to 6 months, suggesting that CO2 could be a safe and effective contrast agent for arterial and cerebrovascular imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral angiography with gaseous carbon dioxide CO2. Shifrin, EG., Plich, MB., Verstandig, AG., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3049465/

The influence of carbon dioxide on brain activity and ... This study investigates how an increase in blood CO 2 , via inhalation of 5% CO 2 , may alter brain activity in humans.

2. withpower.com withpower.com/trial/phase-hypoxia-2020-2e12a

Carbon Dioxide Challenge for Brain Blood Flow Acetazolamide, a carbonic anhydrase inhibitor, significantly increased cerebral blood flow (CBF) by up to 75% within 25 minutes of intravenous injection in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9019094/

CO2 signaling mediates neurovascular coupling in the ... A systematic review of the literature data shows that CO2 and increased neuronal activity recruit the same vasodilatory signaling pathways.

4. tandfonline.com tandfonline.com/doi/full/10.1080/14756366.2021.1907575

Protective effects of carbonic anhydrase inhibition in brain ... CAIs counteracted neuronal loss, reduced microglia activation and partially counteracted astrocytes degeneration inducing protection from functional and tissue ...

5. frontiersin.org frontiersin.org/journals/neuroenergetics/articles/10.3389/neuro.14.007.2009/full

The possible role of CO 2 in producing a post-stimulus CBF ... Our results suggest that increased cerebral blood flow during stimulation causes CO 2 washout which then results in a post-stimulus hypocapnia induced ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10859760/

Carbonic anhydrase, its inhibitors and vascular function - PMC CAIs have been shown to dilate vessels and increase blood flow in both the cerebral and ocular vasculature. Similar effects of CAIs on vascular ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK53082/

Control of Cerebral Blood Flow - NCBI - NIH The brain uses ~20% of available oxygen for normal function, making tight regulation of blood flow and oxygen delivery critical for survival.

8. mdpi.com mdpi.com/1422-0067/22/9/5029

Role of Carbonic Anhydrase in Cerebral Ischemia and ... The loss of cerebral blood flow leads to reduced oxygen and glucose supply and a subsequent switch to the glycolytic pathway, which leads to ...

9. osha.gov osha.gov/hazcom/ghd053107

Guidance For Hazard Determination | Occupational Safety ... This document is designed to help manufacturers and importers of chemicals identify chemical hazards so that employees and downstream users can be informed ...