A Study of Two Methodologies for Measuring Blood Flow in the Brain in Response to Non-Drug Stimuli (P08085/MK-0000-180)

Study Overview
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Brief Summary
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This study will identify a dose of ferumoxytol that can reliably detect changes in blood flow/volume in response to non-drug stimuli. The study will determine whether signal detection for functional magnetic resonance imaging (fMRI) using ferumoxytol is better than that for blood oxygen level-dependent (BOLD) fMRI in response to sensory stimulation. The following procedures will be conducted in each of two study periods: arterial spin labeling (ASL) imaging study with increasing exposure to carbon dioxide (CO2); BOLD fMRI study with sensory stimulation; MRI studies with sensory stimulation in the presence of increasing doses of ferumoxytol; MRI study with increasing exposure to CO2 in the presence of ferumoxytol. There will be a 3-week interval between the two study periods. The study will enroll 8 subjects, but an additional 4 subjects are permitted to enroll to preserve study power.

Detailed Description
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Study Design: Translational Medicine - Imaging Platform Development

Official Title
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A Pilot Clinical Trial to Study Arterial Spin Labeling and USPIO-enhanced MRI Methodologies for Measuring Hemodynamic Responses to Non-Drug Stimuli in Healthy Subjects

Conditions
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Functional Magnetic Resonance Imaging

Intervention / Treatment
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* Procedure: fMRI with sensory stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant weighs approximately 55-75 kg and has a Body Mass Index (BMI) of 18-25 kg/m^2 Participant is in good health Participant is a nonsmoker and/or has not used nicotine or nicotine-containing products for at least 6 months Exclusion Criteria: Participant has a contraindication to MRI including cardiac pacemaker, brain aneurysm clip, implanted neurostimulator, insulin pump, cochlear implant, metal slivers in the eyes, or any other MRI-incompatible metal implants that cannot be safely removed Participant has a condition that would limit his ability to complete MRI procedures, such as claustrophobia or chronic back pain Participant plans to undergo MRI studies in the 3 months following the post-study visit Participant has a history of hemochromatosis or other conditions of iron overload or disease of iron metabolism Participant has a known sensitivity to ferumoxytol or iron-containing products or has a history of severe allergies, anaphylactic reaction, or intolerance to drugs and/or foods Participant has a history of stroke, chronic seizures, or major neurological disorder Participant is unable to refrain from the use of any medication, including prescription and non-prescription drugs or herbal remedies from approximately 2 weeks prior to the first dose of ferumoxytol until the post-study visit Participant has a history of significant head injury/trauma with loss of consciousness lasting for 15 minutes and one or more of the following: a) recurring seizures resulting from head injury; b) persistent neurological or cognitive sequelae of the injury; c) cognitive rehabilitation following the injury

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Participants<br>fMRI studies with sensory stimulation in the presence of 0 mg, 250 mg, 350 mg, and 510 mg cumulative doses of ferumoxytol | Procedure: fMRI with sensory stimulation<br>* BOLD fMRI study with sensory stimulation followed by fMRI in the presence of increasing concentrations of ferumoxytol (Feraheme™)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnitude of the MRI percent signal change in response to sensory stimulation without administration of ferumoxytol (BOLD fMRI) |  | 45 minutes after initiation of imaging procedures | 
| Magnitude of the MRI percent signal change in response to sensory stimulation following administration of the first dose of ferumoxytol (250 mg) |  | 55 minutes after initiation of imaging procedures | 
| Magnitude of the MRI percent signal change in response to sensory stimulation following administration of the second dose of ferumoxytol (100 mg, total cumulative dose of 350 mg) |  | 70 minutes after initiation of imaging procedures | 
| Magnitude of the MRI percent signal change in response to sensory stimulation following administration of the third dose of ferumoxytol (180 mg, total cumulative dose of 510 mg) |  | 85 minutes after initiation of imaging procedures | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brain imaging