Ferumoxytol-enhanced Brain MRI in HIV-associated Neurocognitive Disorders

This study has been completed.
Sponsor:
Collaborator:
Oregon Health and Science University
Information provided by (Responsible Party):
Beau Nakamoto, University of Hawaii
ClinicalTrials.gov Identifier:
NCT01665846
First received: August 13, 2012
Last updated: August 15, 2012
Last verified: August 2012
  Purpose

The purpose of this study is to describe the radiologic findings on brain MRI after ferumoxytol administration in HIV-infected patients with cognitive impairment.


Condition Intervention Phase
HIV Dementia
Drug: Ferumoxytol
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Hawaii:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 4
Study Start Date: July 2011
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ferumoxotyol
Brain MRI will be performed before and 48 +/- 8 hours after ferumoxytol administration.
Drug: Ferumoxytol
A dose of 4 mg/kg of ferumoxytol up to a maximum of 510 mg of elemental iron will be administered.
Other Name: FERAHEME

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection as documented by ELISA and confirmed by Western blot, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA by RT-PCR or DNA at any time prior to study entry.
  • Receipt of antiretroviral (ARV) medication uninterrupted for at least 6 months leading up to the screening period with demonstrated plasma HIV RNA < 48 copies/ml within the last 6 months.
  • Willingness for both males and females of childbearing potential to utilize 2 effective contraception methods (2 separate forms, one of which must be an effective barrier method), be non-heterosexually active or have a an exclusive vasectomized partner from screening throughout the duration of the study treatment and for 30 days following the last dose of study drugs.
  • Age >18 years.
  • Ability and willingness to provide written informed consent
  • HIV DNA > 10 copies/106 CD14+ PBMCs
  • Mild or greater cognitive impairment as indicated by global NPZ8 z-score < -0.5 with a neurocognitive abnormality (defined as a z-score < -0.5) in at least one cognitive domain characteristic of HAD (i.e., executive function, psychomotor speed, memory).

Exclusion Criteria:

  • Requirement for acute therapy for other AIDS-defining illness or other serious medical illnesses (in the opinion of the site investigator) within 14 days prior to study entry.
  • Known allergic or hypersensitivity reaction to FERAHEME, parental iron, parental dextran, parental iron-dextran, or parental iron-polysaccharide preparations
  • Known history of an iron overload syndrome (e.g., hereditary hemochromatosis, porphyria cutanea tarda)
  • Medical conditions (e.g., chronic hemolytic anemia) which requires frequent blood transfusions
  • Taking oral iron supplementation
  • Any factor that precludes MRI scan including presence of metal or exposure to metal work (e.g. metal grinder/worker) and claustrophobia
  • Past or present HIV opportunistic infection of the brain, learning disability, head injury with prolonged loss of consciousness or cognitive sequelae, or other non-HIV risk factor that in the opinion of the principal investigator (PI) may impact cognitive performance.
  • History of epilepsy requiring treatment with an antiepileptic
  • Other chronic illnesses including insulin-dependent diabetes, autoimmune diseases, and endocrinopathies, except subjects on stable physiologic replacement therapy for low testosterone or thyroid levels
  • Current active substance or alcohol dependence or positive urine toxicology screen.
  • Pregnancy or breast-feeding, intent to become pregnant during the course of the study.
  • Any condition which, in the opinion of the investigator, would compromise the subject's ability to participate in the study
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) greater than 2x upper limits of normal on pre-entry baseline laboratory safety assessment prior to study enrollment.
  • Elevated iron levels on pre-entry baseline laboratory safety assessment prior to study enrollment.
  • Hematocrit > 52% or Hemoglobin > 18 g/dL on pre-entry baseline laboratory safety assessment prior to study enrollment.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01665846

Locations
United States, Hawaii
Hawaii Center for AIDS
Honolulu, Hawaii, United States, 96816
Sponsors and Collaborators
University of Hawaii
Oregon Health and Science University
Investigators
Principal Investigator: Beau K Nakamoto, MD, PhD University of Hawaii, Hawaii Center for AIDS, John A Burns School of Medicine
  More Information

Publications:
Responsible Party: Beau Nakamoto, Assistant Professor, University of Hawaii
ClinicalTrials.gov Identifier: NCT01665846     History of Changes
Other Study ID Numbers: H015
Study First Received: August 13, 2012
Last Updated: August 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Hawaii:
HIV associated neurocognitive disorders
MRI
Ferumoxytol

Additional relevant MeSH terms:
AIDS Dementia Complex
Dementia
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Ferrosoferric Oxide
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Parenteral Nutrition Solutions
Pharmaceutical Solutions

ClinicalTrials.gov processed this record on August 20, 2014