Ferumoxytol-enhanced Imaging and Mapping in neuroAIDS

Sponsor

Beau Nakamoto (Other)

Overall Status

Completed

CT.gov ID

NCT02678767

Collaborator

Hawaii Pacific Health (Other), University of Hawaii (Other), National Institute of Neurological Disorders and Stroke (NINDS) (NIH)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
AIDS Dementia Complex	Drug: Ferumoxytol	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Screening

Official Title:

Ferumoxytol-enhanced Imaging and Quantitative Susceptibility Mapping in neuroAIDS

Study Start Date :

Feb 1, 2015

Actual Primary Completion Date :

Sep 1, 2017

Actual Study Completion Date :

Sep 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Ferumoxytol 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 Other Names: Feraheme
Active Comparator: 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	Drug: Ferumoxytol 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 Other Names: Feraheme
Active Comparator: 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	Drug: Ferumoxytol 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 Other Names: Feraheme

Arm

Intervention/Treatment

Experimental: 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

Drug: Ferumoxytol

Other Names:

Feraheme

Active Comparator: HIV+ without neurocognitive impairment

Drug: Ferumoxytol

Other Names:

Feraheme

Active Comparator: HIV- without neurocognitive impairment

Drug: Ferumoxytol

Other Names:

Feraheme

Outcome Measures

Primary Outcome Measures

Change in the proportion of abnormal MRIs [Change from Baseline MRI at 4-6 weeks post-infusion MRI]
The proportion of abnormal MRIs will be compared for each group.

Secondary Outcome Measures

Change in quantitative susceptibility mapping (QSM) [Change from Baseline MRI at 4-6 weeks post-infusion MRI]
Use of QSM to quantitate ferumoxytol accumulation in the brain

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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