HIV DementiaPhase 1NCT01665846
Ferumoxytol-enhanced Brain MRI in HIV-associated Neurocognitive Disorders
A Phase 1 study testing Ferumoxytol in people with HIV Dementia, run by University of Hawaii at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- HIV Dementia
- What is being tested?
- Ferumoxytol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Jun 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Neuroimaging Correlates of Monocyte/Macrophage Infiltration in HIV-infected Individuals: A Cross-sectional Pilot Study Using IV Ferumoxytol
The purpose of this study is to describe the radiologic findings on brain MRI after ferumoxytol administration in HIV-infected patients with cognitive impairment.
Read the 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.
- Conditions
- HIV Dementia
- Being tested
- Ferumoxytol
- Keywords
- HIV associated neurocognitive disorders, MRI, Ferumoxytol
- Medical subject headings
- AIDS Dementia Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FerumoxytolDrug
Also called FERAHEME
A dose of 4 mg/kg of ferumoxytol up to a maximum of 510 mg of elemental iron will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Ferumoxotyol | Experimental | Brain MRI will be performed before and 48 +/- 8 hours after ferumoxytol administration. Receives: Drug: Ferumoxytol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post-ferumoxytol enhancement on Brain MRI
The location and extent of ferumoxytol enhancement within the brain will be described.
Measured: 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
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2012 (estimated)
- Study startJul 2011
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV DementiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Hawaii
- Sponsor type
- University, hospital or other
- Collaborators
- Oregon Health and Science University
- Responsible party
- Principal investigator, Beau Nakamoto, University of Hawaii
- Investigators
- Beau K Nakamoto, MD, PhD, Principal investigator, University of Hawaii, Hawaii Center for AIDS, John A Burns School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01665846
- Sponsor's protocol ID
- H015
- Status last verified
- May 2018
- First submitted
- 13 Aug 2012
- Last updated
- 1 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 18843256
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroimaging Correlates of Monocyte/Macrophage Infiltration in HIV-infected Individuals: A Cross-sectional Pilot Study Using IV Ferumoxytol
- ClinicalTrials.gov ID
- NCT01665846
- Acronym / sponsor ID
- H015
- Conditions
- HIV Dementia
- Keywords
- HIV associated neurocognitive disorders, MRI, Ferumoxytol
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of HawaiiUniversity, hospital or other
- Collaborators
- Oregon Health and Science University
- Study start
- Jul 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 15 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to describe the radiologic findings on brain MRI after ferumoxytol administration in HIV-infected patients with cognitive impairment.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ferumoxotyol | Experimental | Drug: FerumoxytolBrain MRI will be performed before and 48 +/- 8 hours after ferumoxytol administration. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FerumoxytolAlso: FERAHEMEA dose of 4 mg/kg of ferumoxytol up to a maximum of 510 mg of elemental iron will be administered. | Drug | Ferumoxotyol |
Primary outcome
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
The location and extent of ferumoxytol enhancement within the brain will be described.
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2018.
- Background: PubMed 18843256Neuwelt 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.
- AMAG PharmaceuticalsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Beau K Nakamoto, MD, PhD principal investigator
University of Hawaii, Hawaii Center for AIDS, John A Burns School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ferumoxytol in people with HIV Dementia, run by University of Hawaii at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01665846, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2018.