Ferumoxytol-enhanced Imaging and Mapping in neuroAIDS

Ferumoxytol-enhanced Imaging and Quantitative Susceptibility Mapping in neuroAIDS

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.

Study Overview

• Status: Completed
• Conditions: AIDS Dementia Complex
• Intervention / Treatment: Drug: Ferumoxytol

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Center for AIDS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beau Nakamoto
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); University of Hawaii; Hawaii Pacific Health
• Investigators: Principal Investigator: Beau Nakamoto, MD, PhD, University of Hawaii

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: February 2, 2016
• First Submitted That Met QC Criteria: February 5, 2016
• First Posted (Estimate): February 10, 2016

Study Record Updates

• Last Update Posted (Actual): October 27, 2017
• Last Update Submitted That Met QC Criteria: October 25, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: HIV; Dementia; Neuroimaging
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Neurocognitive Disorders; HIV Infections; Dementia; AIDS Dementia Complex; Hematinics; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Ferrosoferric Oxide
• Other Study ID Numbers: 2013-077 (Other Identifier: CCRRC); H032 (Other Identifier: Hawaii Center for AIDS); 1R21NS087951-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO