Ferumoxytol-enhanced Brain MRI in HIV-associated Neurocognitive Disorders
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Neuroimaging Correlates of Monocyte/Macrophage Infiltration in HIV-infected Individuals: A Cross-sectional Pilot Study Using IV Ferumoxytol|
- Post-ferumoxytol enhancement on Brain MRI [ Time Frame: 48 hour following administration of a dose of 4 mg/kg of feruomoxytol up to a maximum of 510 mg of elemental iron ] [ Designated as safety issue: No ]The location and extent of ferumoxytol enhancement within the brain will be described.
- Safety [ Time Frame: 1 hour and 1 month following administration of a dose of 4 mg/kg of ferumxotyol up to a maximum of 510 mg of elemental iron ] [ Designated as safety issue: Yes ]The rate of overall grade > 2 toxicities (categorized by the NIAID Division of AIDS adverse events table) during ferumoxytol infusion and 1 month post-ferumoxytol infusion will be assessed.
|Study Start Date:||July 2011|
|Study Completion Date:||June 2012|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
Brain MRI will be performed before and 48 +/- 8 hours after ferumoxytol administration.
A dose of 4 mg/kg of ferumoxytol up to a maximum of 510 mg of elemental iron will be administered.
Other Name: FERAHEME
The continued existence of cognitive dysfunction in HIV infected individuals in the era of effective antiretroviral therapy may be, in part, secondary to the failure of current antiretroviral regimens to eradicate the pool of HIV-infected and activated monocytes within the bloodstream. Trafficking of such HIV infected and activated blood monocytes into the brain parenchyma is believed to introduce HIV into the brain and precipitate immune activation and inflammation, ultimately leading to neuronal degeneration.
Ferumoxytol is an ultrasmall superparamagnetic iron-oxide (USPIO), which is FDA-approved for intravenous iron-replacement therapy in anemic patients with chronic kidney disease. The paramagnetic properties of ferumoxytol also allow it to be used as a MRI contrast agent. Ferumoxytol is avidly taken up by circulating monocytes and reactive astrocytes, microglia, and dendritic cells within the brain, making it potentially a novel biomarker for HIV-associated cognitive impairment given the role of monocytes in its pathogenesis.
This proposal intends to investigate the possible use of ferumoxytol (a new MRI contrast agent) as a biomarker for HIV-associated cognitive impairment and to assess the safety and tolerability of ferumoxytol in HIV-infected individuals.
Hypotheses to be tested:
- HIV-infected subjects with undetectable plasma HIV RNA levels and detectable levels of HIV DNA in CD14+ peripheral blood mononuclear cells (PBMCs) and impairment on neurocognitive testing will demonstrate ferumoxytol contrast enhancement in the perivascular regions of the brain consistent with monocyte/macrophage infiltration in these regions.
- Ferumoxytol can be safely administered to HIV-infected subjects.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01665846
|United States, Hawaii|
|Hawaii Center for AIDS|
|Honolulu, Hawaii, United States, 96816|
|Principal Investigator:||Beau K Nakamoto, MD, PhD||University of Hawaii, Hawaii Center for AIDS, John A Burns School of Medicine|