Ferumoxytol-enhanced Imaging and Mapping in neuroAIDS

Study Overview
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Brief Summary
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This project will investigate the ability of a novel MRI contrast agent to identify and quantitate ongoing monocyte/macrophage (M/MΦ)-mediated inflammation in the brains of HIV-infected individuals.

Detailed Description
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HIV-associated neurocognitive disorders (HAND) continue to be prevalent despite effective combination antiretroviral therapy (cART) and have a significant impact on morbidity and quality of life. Monocytes/macrophages (M/MΦ) are believed to play a critical role in the pathogenesis of HAND. Neuroimaging HIV research has not focused on assessing M/MΦ-mediated inflammation in the brain. Currently, no neuroimaging modality exists that can define the extent of active inflammation due to M/MΦ in HAND either as a clinical diagnostic tool or to assist in defining objective improvement in clinical trials addressing HAND. Ferumoxytol is an ultra-small iron oxide MRI contrast agent avidly taken up by circulating M/MΦ. The investigators hypothesize that ferumoxytol-based imaging can identify ongoing inflammation due to perivascular M/MΦ which is believed to represent a key pathologic correlate of HAND.

Official Title
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Ferumoxytol-enhanced Imaging and Quantitative Susceptibility Mapping in neuroAIDS

Conditions
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AIDS Dementia Complex

Intervention / Treatment
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* Drug: Ferumoxytol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 40-65 years Plasma HIV RNA < 48 copies/ml (HIV+ subjects only) On stable cART >= 1 year (HIV+ subjects only) Global neuropsychological (NP) score <-0.5 in at least one cognitive domain known to be affected by HIV (neurocognitively impaired subjects only) Documentation of negative HIV infection by an FDA approved test (HIV- subjects only) Exclusion Criteria: Active substance use History of myocardial infarct or stroke Diabetes Chronic hepatitis C virus (HCV) infection Uncontrolled major affective disorder, active psychosis, central nervous system disease that affects the brain structure, or other uncontrolled chronic medical condition that in the opinion of the investigator may impact NP testing or the study outcome Psychoactive or other medications which may impact NP testing Factors that preclude MRI Known hypersensitivity to ferumoxytol History of laboratory measurements consistent with an iron overload syndrome Medical conditions that require frequent blood transfusions Taking oral iron supplements Elevated iron levels Any condition, which in the opinion of the investigator, would compromise the subject's ability to participate Multiple drug allergies that may pose a greater risk of anaphylaxis associated with ferumoxytol Pregnant, unwillingness to practice birth control, or breastfeeding Unable to give informed consent

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIV+ with neurocognitive disorder<br>All subjects will receive neurocognitive testing. Subjects will have a brain MRI prior to drug infusion. A one-time ferumoxytol IV infusion will be given at a dose of 4mg Fe/kg up to a maximum of 510mg of elemental iron delivered at a rate of 1ml/sec. A second brain MRI will be completed post-infusion | Drug: Ferumoxytol<br>* All subjects will receive neurocognitive testing. Subjects will have a brain MRI prior to drug infusion. A one-time ferumoxytol IV infusion will be given at a dose of 4mg Fe/kg up to a maximum of 510mg of elemental iron delivered at a rate of 1ml/sec. A second brain MRI will be completed post-infusion<br>* Other names: Feraheme;|
| Active Comparator: HIV+ without neurocognitive impairment<br>All subjects will receive neurocognitive testing. Subjects will have a brain MRI prior to drug infusion. A one-time ferumoxytol IV infusion will be given at a dose of 4mg Fe/kg up to a maximum of 510mg of elemental iron delivered at a rate of 1ml/sec. A second brain MRI will be completed post-infusion | Drug: Ferumoxytol<br>* All subjects will receive neurocognitive testing. Subjects will have a brain MRI prior to drug infusion. A one-time ferumoxytol IV infusion will be given at a dose of 4mg Fe/kg up to a maximum of 510mg of elemental iron delivered at a rate of 1ml/sec. A second brain MRI will be completed post-infusion<br>* Other names: Feraheme;|
| Active Comparator: HIV- without neurocognitive impairment<br>All subjects will receive neurocognitive testing. Subjects will have a brain MRI prior to drug infusion. A one-time ferumoxytol IV infusion will be given at a dose of 4mg Fe/kg up to a maximum of 510mg of elemental iron delivered at a rate of 1ml/sec. A second brain MRI will be completed post-infusion | Drug: Ferumoxytol<br>* All subjects will receive neurocognitive testing. Subjects will have a brain MRI prior to drug infusion. A one-time ferumoxytol IV infusion will be given at a dose of 4mg Fe/kg up to a maximum of 510mg of elemental iron delivered at a rate of 1ml/sec. A second brain MRI will be completed post-infusion<br>* Other names: Feraheme;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the proportion of abnormal MRIs | The proportion of abnormal MRIs will be compared for each group. | Change from Baseline MRI at 4-6 weeks post-infusion MRI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quantitative susceptibility mapping (QSM) | Use of QSM to quantitate ferumoxytol accumulation in the brain | Change from Baseline MRI at 4-6 weeks post-infusion MRI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Dementia, Neuroimaging