Ferumoxytol-enhanced Brain MRI in HIV-associated Neurocognitive Disorders

NCT01665846 | Completed Phase 1

• 1 other identifier: H015
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

HIV Dementia

Keywords

HIV associated neurocognitive disorders; MRI; Ferumoxytol

Outcome Measures

Primary Outcomes (1)

• Post-ferumoxytol enhancement on Brain MRI

  The location and extent of ferumoxytol enhancement within the brain will be described.

  48 hour following administration of a dose of 4 mg/kg of feruomoxytol up to a maximum of 510 mg of elemental iron

Secondary Outcomes (1)

• Safety

  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

Study Arms (1)

Ferumoxotyol

EXPERIMENTAL

Brain MRI will be performed before and 48 +/- 8 hours after ferumoxytol administration.

Drug: Ferumoxytol

Interventions

Ferumoxytol DRUG

A dose of 4 mg/kg of ferumoxytol up to a maximum of 510 mg of elemental iron will be administered.

Also known as: FERAHEME

Ferumoxotyol

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Hawaii: lead
• Oregon Health and Science University: collaborator

Study Sites (1)

Hawaii Center for AIDS

Honolulu, Hawaii, 96816, United States

Location

Related Publications (1)

• Neuwelt EA, Hamilton BE, Varallyay CG, Rooney WR, Edelman RD, Jacobs PM, Watnick SG. Ultrasmall superparamagnetic iron oxides (USPIOs): a future alternative magnetic resonance (MR) contrast agent for patients at risk for nephrogenic systemic fibrosis (NSF)? Kidney Int. 2009 Mar;75(5):465-74. doi: 10.1038/ki.2008.496. Epub 2008 Oct 8.

  PMID: 18843256 BACKGROUND

Related Links

• AMAG Pharmaceuticals

MeSH Terms

Conditions

AIDS Dementia Complex

Interventions

Ferrosoferric Oxide

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Ferrous Compounds; Minerals

Study Officials

• Beau K Nakamoto, MD, PhD

  University of Hawaii, Hawaii Center for AIDS, John A Burns School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 13, 2012
• First Posted: August 15, 2012
• Study Start: July 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: June 1, 2018

Record last verified: 2018-05

Locations

US (1)