Ferumoxytol-enhanced Imaging and Mapping in neuroAIDS

Beau Nakamoto

Status and phase: Completed; Phase 2

Conditions: AIDS Dementia Complex

Treatments: Drug: Ferumoxytol

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02678767

1R21NS087951-01A1 (U.S. NIH Grant/Contract)

2013-077 (Other Identifier)

H032 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 30 patients

Sex: All

Ages: 40 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Screening

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

HIV+ with neurocognitive disorder

Experimental group

Description:

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

Treatment:

Drug: Ferumoxytol

HIV+ without neurocognitive impairment

Active Comparator group

Description:

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

Treatment:

Drug: Ferumoxytol

HIV- without neurocognitive impairment

Active Comparator group

Description:

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

Treatment:

Drug: Ferumoxytol