Xenon-129 fMRI for Alzheimer's Disease

Overseen By Alla Reznik, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Thunder Bay Regional Health Research Institute

Disqualifiers: Substance abuse, Psychotic disorder, Cardiac, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to enhance brain imaging techniques to better understand and treat Alzheimer's disease. It uses a special type of MRI that involves inhaling xenon-129 gas to create clearer images of brain function. The study seeks individuals with Alzheimer's, who need a doctor's diagnosis, and healthy volunteers without neurological issues. Participants should be able to hold their breath for 20 seconds and have normal or corrected vision. This research could help develop more effective drugs for Alzheimer's in the future. As an Early Phase 1 trial, the research focuses on understanding how the imaging technique works in people, offering participants a chance to contribute to groundbreaking advancements in Alzheimer's treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators for clarification.

What prior data suggests that this imaging technique is safe for humans?

Research has shown that hyperpolarized xenon-129 MRI is generally safe and well-tolerated. Studies involving both healthy individuals and people with Alzheimer's disease have reported no serious side effects. During these MRI scans, participants breathe in a gas called NeuroXene, which contains xenon-129, an inert gas that does not easily react with other substances.

In several studies, people who inhaled xenon-129 experienced few issues. Some felt slightly dizzy, but this feeling quickly subsided. These studies confirm that using xenon-129 for MRI is safe for humans.

Since this trial is in an early phase, it primarily focuses on assessing safety and determining the best way to use this imaging tool. This phase is crucial for identifying any problems before testing on larger groups. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a novel way to image the brain in Alzheimer's disease using hyperpolarized Xenon-129 in MRI scans. Unlike traditional imaging methods that primarily rely on proton fMRI, this technique allows for enhanced visualization by leveraging the unique properties of Xenon-129 gas. The dual-tuned head coil used in this study can capture both conventional and hyperpolarized gas images, potentially providing deeper insights into brain function and structure. By improving our understanding of brain changes in Alzheimer's, this approach could pave the way for earlier diagnosis and better monitoring of the disease.

What evidence suggests that this imaging method is effective for Alzheimer's disease?

Research has shown that Hyperpolarized Xenon-129 MRI holds promise for studying brain function in Alzheimer's disease. This trial involves participants with Alzheimer's disease and healthy volunteers inhaling NeuroXene, a form of xenon-129, to produce clearer brain images. Studies have demonstrated that Hyperpolarized Xenon-129 MRI can effectively highlight changes in brain activity and blood flow related to Alzheimer's. It has been tested in animals, healthy individuals, and patients with Alzheimer's, offering valuable insights. Although more research is needed, early findings suggest it could become a useful tool for understanding and potentially improving treatments for Alzheimer's disease. ^{2 4 5 6 7}

Who Is on the Research Team?

Mitchell Albert, Ph.D.

Principal Investigator

Thunder Bay Regional Health Research Institute

Are You a Good Fit for This Trial?

This trial is for healthy adults and those with Alzheimer's disease, aged 18-85 or 60-85 respectively. Participants must speak English, have at least 8 years of education, be able to consent and hold their breath for 20 seconds. Those with Alzheimer's need a MoCA score of at least 16 and a caregiver present during the study.

Inclusion Criteria

Self-reported proficiency in English language

Equal to or more than 8 years of education

MoCA score no less than 26

Exclusion Criteria

I am not pregnant nor planning to become pregnant.

Is a student currently enrolled in a course at Lakehead University where the Principal Investigator (PI) is the instructor

Is a student currently enrolled in a degree program at Lakehead University where the PI is their direct thesis supervisor

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Imaging

Participants undergo MRI scanning using traditional proton fMRI and hyperpolarized xenon-129 fMRI

1 visit

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 1H-129Xe Dual-Tuned Quadrature Head Coil
• Hyperpolarized Xenon-129

Trial Overview The study tests hyperpolarized xenon functional brain MRI against traditional proton fMRI in detecting brain function changes in Alzheimer's. It aims to improve drug development by providing more sensitive measurements of brain activity.

How Is the Trial Designed?

Group I: Healthy Volunteers Experimental Treatment 4 Interventions

Healthy volunteers will inhale NeuroXene using various breathing methods. The CMRS 1H-129Xe dual-tuned quadrature head coil will be used to acquire MRI images of the human brain after inhalation of NeuroXene. The coil permits the acquisition of both conventional proton and HP xenon gas images. Two types of MRI scans will be performed: Traditional proton fMRI and Hyperpolarized Xenon-129 fMRI. The order of scans will be randomized to account for bias caused by scan order.

Group II: Alzheimer's Disease Participants Experimental Treatment 4 Interventions

Alzheimer's disease participants will inhale NeuroXene using various breathing methods. The CMRS 1H-129Xe dual-tuned quadrature head coil will be used to acquire MRI images of the human brain after inhalation of NeuroXene. The coil permits the acquisition of both conventional proton and HP xenon gas images. Two types of MRI scans will be performed: Traditional proton fMRI and Hyperpolarized Xenon-129 fMRI. The order of scans will be randomized to account for bias caused by scan order.

Who Is Running the Clinical Trial?

Thunder Bay Regional Health Research Institute

Lead Sponsor

Trials

11

Recruited

860+

Thunder Bay Regional Research Institute

Lead Sponsor

Trials

9

Recruited

620+

Thunder Bay Regional Health Sciences Centre

Collaborator

Trials

10

Recruited

3,300+

Lakehead University

Collaborator

Trials

29

Recruited

3,900+

Published Research Related to This Trial

Functional MRI (fMRI) is a safe and noninvasive imaging tool that allows for repeated scans, making it ideal for studying brain activation in patients with neurological and neuropsychiatric disorders over time.

fMRI has shown potential in identifying abnormal brain activity, understanding neuroplasticity, and serving as a predictive biomarker for disease progression, highlighting its utility in both clinical trials and basic research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in functional magnetic resonance imaging: technology and clinical applications. Dickerson, BC.[2020]

Inhalation of hyperpolarized xenon-129 (129Xe) was found to be safe and well tolerated among 44 subjects, including healthy individuals and patients with chronic obstructive pulmonary disease (COPD), with no serious adverse events reported.

While 91% of participants experienced mild and transient symptoms such as dizziness and euphoria, these symptoms resolved quickly without the need for clinical intervention, indicating that the procedure is generally safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic obstructive pulmonary disease: safety and tolerability of hyperpolarized 129Xe MR imaging in healthy volunteers and patients. Driehuys, B., Martinez-Jimenez, S., Cleveland, ZI., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9314594/

Hyperpolarized 129Xe imaging of the brain: Achievements ... HP 129Xe MRI imaging of the brain has been performed in animals, healthy human subjects, and in patients with Alzheimer's disease and stroke. In this review, ...

2. withpower.com withpower.com/trial/early-phase-1-alzheimer-disease-5-2016-9dc76

Xenon-129 fMRI for Alzheimer's Disease · Info for Participants This trial uses a special MRI scan with a gas called xenon-129 to get clearer pictures of the brain. It targets people being assessed for brain function to ...

3. mdpi.com mdpi.com/2075-4418/15/4/474

Hyperpolarized Xenon-129 MRI: Narrative Review of ... Several investigators have evaluated the effectiveness of 129XeMRI in assessing lung function in patients with CF. Not surprisingly, 129XeMRI is reliable in ...

4. ctv.veeva.com ctv.veeva.com/study/hp-xenon-129-fmri-of-healthy-volunteers-and-participants-with-alzheimers-disease

HP Xenon-129 fMRI of Healthy Volunteers and Participants ... This study involves imaging participants' brains using MRI. The goal is to develop a high-resolution, high-sensitivity imaging tool, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7554935/

Hyperpolarized 129Xe Time-of-Flight MR Imaging ... The last achievements in the field of HP 129Xe MRI allowed the investigation of cerebral perfusion changes associated with Alzheimer's disease [34] and stroke [ ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6023430/

Inhaled Xenon Washout as a Biomarker of Alzheimer's ... This study investigates the potential utility of a series of novel AD biomarkers, the sixty second 129 Xe retention time, and the xenon washout parameter.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02195206

Hyperpolarized Xenon-129 Lung and/or Brain Magnetic ... In this pilot study, MRI of the lungs and/or brain of healthy adult volunteers will be performed at 3Tesla to assess image quality using a ...