Ferumoxytol-enhanced Imaging and Quantitative Susceptibility Mapping in neuroAIDS

Beau Nakamoto1 site in 1 country30 target enrollmentFebruary 2015

Overview

Brief Summary

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

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.

Registry

clinicaltrials.gov

Start Date

February 2015

End Date

September 2017

Last Updated

8 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Beau Nakamoto

Responsible Party

Sponsor Investigator

Principal Investigator

Beau Nakamoto

Assistant Professor of Medicine

University of Hawaii

Eligibility Criteria

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
•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

Arms & Interventions

HIV+ with neurocognitive disorder

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

Intervention: Ferumoxytol

HIV+ without neurocognitive impairment

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

Intervention: Ferumoxytol

HIV- without neurocognitive impairment

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

Intervention: Ferumoxytol