MRI Techniques with Alcohol Challenge for Neuroimaging

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Metronidazole

Disqualifiers: MRI contraindications, Alcohol abuse, Liver pathology

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

Compensation: Varies

Number of Visits: 3

10 Participants Needed

Trial Summary

What is the purpose of this trial?

Intracranial interstitial fluid (ISF) flow is crucial for adequate clearance of extracellular waste products from the brain parenchyma. Recent demonstrations have shown that a deficiency in flow leads to the accumulation of such waste products in neurodegenerative disorders. Unfortunately, no clinical investigation that gives a quantitative measure of ISF flow exists. Such a test could prove very useful in the clinical setting for multiple neurologic disorders by providing a measure of potential diagnostic importance, as well as yielding a means to monitor response to treatment. The investigators hypothesize that such an investigation can be developed using magnetic resonance spectroscopy to give a quantitative measure of ISF flow, using spectroscopy of ethanol as a dynamic marker of interstitial fluid. Beneficially, the approach is non-invasive. This pilot project aims to develop this technique with proof of concept in healthy volunteers (males in the age range of 20-75). This pilot project aims to develop the technique, demonstrating its ability to detect ISF flow and potential differences in rates among healthy volunteers. Success at this stage will give rise to this technique being extended to studies involving individuals with various forms of intracranial pathology for comparison with values seen in healthy individuals, with the ultimate goal of it providing a measure of diagnostic significance in multiple clinical scenarios.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications like metronidazole that could cause a reaction with alcohol.

What data supports the effectiveness of this treatment involving alcohol ingestion and MRI techniques?

The research shows that MRI techniques, like magnetic resonance spectroscopy (MRS), can effectively measure alcohol concentration in the brain, providing insights into how alcohol affects brain function. This suggests that these imaging methods are useful for studying the impact of alcohol on the brain in real-time. ^{1 2 3 4 5}

Is it safe to use MRI techniques with alcohol challenge for neuroimaging in humans?

Research involving MRI techniques with alcohol challenge in humans has shown that it is feasible to measure alcohol concentrations in the brain using magnetic resonance spectroscopy (MRS). Studies have been conducted on both humans and non-human primates, and while they focus on measuring alcohol levels, they do not report any specific safety concerns related to the procedure itself. ^{1 3 4 6 7}

How does the MRI technique with alcohol challenge differ from other treatments for alcohol-related conditions?

This treatment is unique because it uses MRI techniques to study how alcohol affects the brain in real-time, providing insights into the distribution and concentration of alcohol in different brain regions. Unlike traditional treatments that focus on managing symptoms or reducing alcohol intake, this approach aims to understand the brain's response to alcohol at a molecular level, which could lead to more targeted therapies in the future. ^{1 3 6 7 8}

Research Team

Greg J Stanisz, PhD

Principal Investigator

Sunnybrook Research Institute

David Mikulis, MD

Principal Investigator

Krembil Research Institute

Eligibility Criteria

This trial is for healthy male volunteers aged 20-75 who drink less than 6 alcoholic beverages per week. Participants must be able to consent, communicate with the researcher, and follow study procedures. They can't join if they have a history of alcohol or substance abuse, liver problems, are taking certain medications like metronidazole, or cannot undergo an MRI.

Inclusion Criteria

Low consumer of ethanol (less than 6 drinks per week where a drink is 1 oz of distilled spirits, 6 oz wine, 12 oz beer)

I can understand and agree to the study's requirements.

Exclusion Criteria

You have a history of excessive alcohol or drug use.

I am on medication that reacts badly with alcohol.

I have a history of liver disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Pre-Experiment Preparation

Participants fast for 6 hours and refrain from alcohol for 12 hours before the experiment

1 day

Experiment

Participants undergo MR acquisition, consume ethanol, and have repeated MR scans for 60-90 minutes

1 day

1 visit (in-person)

Post-Experiment Monitoring

Participants are monitored until blood ethanol levels are below 0.05% and feel safe to leave

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any delayed effects and data analysis is performed

1 week

Treatment Details

Interventions

• Alcohol ingestion
• Blood sampling
• ClearMate
• Magnetization Transfer Imaging
• Multi-voxel MRSI
• Single-voxel MRS

Trial Overview The study is testing a new non-invasive method using magnetic resonance spectroscopy (MRS) and ethanol as a marker to measure fluid flow in the brain. The goal is to develop this technique in healthy individuals first before applying it to patients with neurological disorders.

Participant Groups

Group I: Single-voxel MRS + ClearMate + Blood Sampling Active Control 4 Interventions

MRS+CM+B

Group II: Multi-voxel MRSI + ClearMate + Blood Sampling Active Control 4 Interventions

MRSI+CM+B

Group III: Magnetization Transfer Imaging + ClearMate + Blood Sampling Active Control 4 Interventions

MTI+CM+B

Group IV: Multi-voxel MRSI + ClearMate Active Control 3 Interventions

MRSI+CM

Group V: Magnetization Transfer Imaging + ClearMate Active Control 3 Interventions

MTI+CM

Group VI: Single-voxel MRS + ClearMate Active Control 3 Interventions

MRS+CM

Group VII: Single-voxel MRS Active Control 2 Interventions

MRS

Group VIII: Magnetization Transfer Imaging Active Control 2 Interventions

MTI

Group IX: Multi-voxel MRSI Active Control 2 Interventions

MRSI

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

References

1. Japan pubmed.ncbi.nlm.nih.gov

Preliminary observation of dynamic changes in alcohol concentration in the human brain with proton magnetic resonance spectroscopy on a 3T MR instrument. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Measurement of ethanol in the human brain using NMR spectroscopy. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Ethanol Kinetics in the Human Brain Determined by Magnetic Resonance Spectroscopy. [2023]

4. England pubmed.ncbi.nlm.nih.gov

In situ postmortem ethanol quantification in the cerebrospinal fluid by non-water-suppressed proton MRS. [2019]

5. England pubmed.ncbi.nlm.nih.gov

In vivo quantification of ethanol kinetics in rat brain. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Indirect imaging of ethanol via magnetization transfer at high and low magnetic fields. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Quantification of ethanol methyl (1)H magnetic resonance signal intensity following intravenous ethanol administration in primate brain. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Magnetic resonance spectroscopic imaging of ethanol in the human brain: a feasibility study. [2019]