HP Xenon-129 fMRI of Healthy Volunteers and Participants With Alzheimer's Disease

Early Phase 1

Terminated

• Conditions: Alzheimer Disease
• Interventions: Other: Traditional Proton fMRI; Other: Hyperpolarized Xenon-129 fMRI; Drug: Hyperpolarized Xenon-129; Device: 1H-129Xe Dual-Tuned Quadrature Head Coil

• Registration Number: NCT02638519
• Lead Sponsor: Thunder Bay Regional Health Research Institute

Brief Summary

This study involves imaging participants' brains using MRI. The goal is to develop a high-resolution, high-sensitivity imaging tool, hyperpolarized xenon functional brain magnetic resonance imaging, which can provide more sensitive measurement of brain function, facilitating the development of drugs for more successful treatment of Alzheimer's disease.

Detailed Description

The described study is a pilot study in which the investigators aim to develop an enhanced sensitivity tool for assessment of neural function. Participation involves at least two study visits no longer than three hours in length each. During visit 1, informed consent and screening for eligibility will take place. During visit 2, fMRI scanning will take place in which participants will complete simple tasks. Two types of MRI scans will be performed: traditional proton fMRI and hyperpolarized xenon-129 fMRI (HP 129Xe fMRI) scans. The trade name for xenon-129 hyperpolarized with a Xemed LLC polarizer is NeuroXene.

Participants will be placed in the 3T MRI at the Thunder Bay Regional Research Institute with a Clinical MR Solutions (CMRS) Dual Brain Coil that fits over their head like a helmet. Several inhalation procedures will be performed by participants when breathing NeuroXene from a tube in the scanner. Preparation and administration of NeuroXene and the CMRS Dual Brain Coil will be carried out according to the SOP's developed by the TBRRI and Xemed LLC.

MRI scanning will be performed with a MR Tech and Registered Respiratory Therapist present. Dispensing of 129Xe will be monitored using a gas dispensing form and a drug accountability log. This study will have a monitor assigned to it from the TBRRI that is not involved in this clinical trial. This is to ensure participant safety and adherence to the protocol.

Study Timeline

• Study First Submitted: 2015-12-03
• Study First Submitted QC: 2015-12-18
• Study First Posted: 2015-12-23
• Study Start: 2016-06-27
• Primary Completion: 2022-04-19
• Study Completion: 2022-04-19
• Status Verified: 2024-08
• Last Update Submitted: 2024-10-08
• Last Update Posted: 2024-10-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 51

Inclusion Criteria

A participant is eligible for inclusion in the study if the individual meets all of the following criteria:

1. Self-reported proficiency in English language.
2. Equal to or more than 8 years of education.
3. Normal or corrected to normal vision.
4. Able to provide informed consent.
5. Able to hold their breath for 20 seconds.

Normal cognition for healthy participant group inclusion criteria:

1. Preserved independence in functional abilities.
2. MoCA score no less than 26.
3. Males and non-lactating females of 18 to 85 years of age.

Alzheimer's disease group inclusion criteria:

1. Participants meet National Institute on Aging-Alzheimer's Association for probable or possible Alzheimer's Disease dementia.
2. MoCA score no less than 16.
3. Males and non-lactating females of 60 to 85 years of age.
4. Have a family member, close friend, or LAR that can be present for the informed consent process and study visits.

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Exclusion Criteria

A participant is ineligible for the study if the individual meets any of the following criteria:

1. Serious underlying medical condition, other, then the condition being investigated, which may affect cognitive function of the participant (in the opinion of the investigator): substance abuse, psychotic or depressive disorder, advanced or poorly controlled cardiac, pulmonary, hepatic, renal, neurological disorders in which the patient has significant speech, visual, motor or cognitive deficit, seizure disorders, endocrine or infectious disease or active malignancy.
2. MRI incompatibility as determined by MR Technologist during MRI screening.
3. Self-identifies as claustrophobic.
4. Female exclusion only: Are or may be pregnant; Planning on becoming pregnant.
5. Is a student currently enrolled in a course at Lakehead University where the Principal Investigator (PI) is the instructor.
6. Is a student currently enrolled in a degree program at Lakehead University where the PI is their direct thesis supervisor.
7. Is currently an employee of the PI at the Thunder Bay Regional Research Institute (TBRRI) and/or Lakehead University.

Normal cognition group exclusion criteria:

1. History of diagnosed neurological disease or injury.

Alzheimer's disease group exclusion criteria:

1. Existing diagnosis of dementia of etiology other than Alzheimer's disease.
2. Acute Delirium on the day of scanning (CAM tool assessment)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy Volunteers	Hyperpolarized Xenon-129 fMRI	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.
Healthy Volunteers	1H-129Xe Dual-Tuned Quadrature Head Coil	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.
Healthy Volunteers	Traditional Proton fMRI	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.
Alzheimer's Disease Participants	Hyperpolarized Xenon-129 fMRI	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.
Alzheimer's Disease Participants	Hyperpolarized Xenon-129	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.
Alzheimer's Disease Participants	1H-129Xe Dual-Tuned Quadrature Head Coil	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.
Alzheimer's Disease Participants	Traditional Proton fMRI	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.
Healthy Volunteers	Hyperpolarized Xenon-129	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.

Primary Outcome Measures

Name	Time	Method
Signal-to-Noise Ratio (SNR)	Three years	All scans will be optimized for the highest SNR possible; No aggregation of data

Secondary Outcome Measures

Name	Time	Method
P-Value	Three years	To be calculated from a students paired t-test for signal change between healthy participant scans and participants with Alzheimer disease

Trial Locations

Locations (1)

Thunder Bay Regional Health Sciences Centre; 🇨🇦 Thunder Bay, Ontario, Canada