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Study of Paroxetine and Fluconazole for the Treatment of HIV Associated Neurocognitive Disorder (ParaFlu)

This study is currently recruiting participants.
Verified September 2012 by Johns Hopkins University
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Ned Sacktor, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01354314
First received: May 13, 2011
Last updated: September 18, 2012
Last verified: September 2012
History of Changes
  Purpose

The purpose of this study is to see if paroxetine and fluconazole are safe and effective as a treatment for problems with memory, concentration, thinking, and judgment in people who are infected with HIV. Paroxetine is an antidepressant approved by the FDA to treat major depression. Fluconazole is an antifungal medication approved by the FDA to treat fungal infections.


Condition Intervention Phase
HIV Associated Neurocognitive Disorder
 Drug: Fluconazole
Drug: Paroxetine
Drug: Paroxetine and Fluconazole
Drug: Placebo
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Pilot Study of Paroxetine and Fluconazole for the Treatment of HIV Associated Neurocognitive Disorder (HAND)

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS Memory
U.S. FDA Resources

Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • CSF lipid and protein markers of oxidative stress [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    CSF lipid and protein markers of oxidative stress [CSF ceramide and (C18:0 levels) and 3-nitrosylated proteins]


Secondary Outcome Measures:
  • Neurocognitive performance [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    Neurocognitive performance as measured by a standard battery of neuropsychological tests

  • Functional performance [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    Functional performance as measured by a standard set of subjective and objective functional assessments.

  • Magnetic resonance spectroscopy (MRS) and arterial spin labeling [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    Analysis of imaging markers as measured by magnetic resonance spectroscopy (MRS) and arterial spin labeling.


Estimated Enrollment: 60
Study Start Date: November 2010
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fluconazole
Fluconazole 100 mg every 12 hours orally per day; placebo in place of paroxetine
 Drug: Fluconazole
One 100 MG capsule taken twice daily, 12 hour dosing
Experimental: Paroxetine
Paroxetine 20 mg orally once per day; placebo in place of fluconazole
 Drug: Paroxetine
Two 10 MG capsules paroxetine once daily in the evening
Experimental: Paroxetine and Fluconazole
Fluconazole 100 mg every 12 hours orally per day and paroxetine 20 mg every evening orally per day
 Drug: Paroxetine and Fluconazole
One capsule 100 MG fluconazole every 12 hours orally per day; Two 10 MG capsules paroxetine orally once daily in the evening
Placebo Comparator: Placebo
Placebo in place of both fluconazole and paroxetine
 Drug: Placebo
One capsule in the morning, three capsules in the evening

Detailed Description:

The study will be a 24 week double-blind, placebo-controlled 2x2 factorial design pilot Phase I/II study in 60 HIV+ individuals with HAND. Participants will be randomly assigned to one of four groups: 1) fluconazole 100 mg every 12 hours orally per day, 2) paroxetine 20mg every evening orally per day, 3) fluconazole 100mg every 12 hours orally per day and paroxetine 20mg every evening orally per day and 4) placebo.

Primary Aim: To obtain preliminary data to evaluate the efficacy of fluconazole and/or paroxetine to decrease CSF lipid and protein markers of oxidative stress [CSF ceramide and (C18:0 levels) and 3-nitrosylated proteins].

Secondary Aims:

i) To evaluate the safety and tolerability of fluconazole and/or paroxetine in HIV+ individuals with HAND ii) To evaluate the effect of fluconazole and/or paroxetine on neurocognitive performance in HIV+ individuals with HAND iii) To evaluate the effect of fluconazole and/or paroxetine on functional performance in HIV+ individuals with HAND iv) To evaluate the CNS penetration of fluconazole and paroxetine after 24 weeks of treatment v) To obtain preliminary data to evaluate the efficacy of fluconazole and/or paroxetine to improve abnormal imaging markers as measured by magnetic resonance spectroscopy (MRS) and arterial spin labeling

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV+ based on ELISA and confirmed by either Western blot or plasma HIV RNA
  • capable of providing informed consent
  • age range: 18-65 years
  • presence of neuropsychological testing impairment as defined by performance at least 1.0 standard deviation below age-matched and education-matched controls on three or more independent neuropsychological tests at the screening visit, or performance at least 2.0 standard deviations below age-matched and education-matched controls on one independent neuropsychological test and at least 1.0 standard deviation below age-matched and education-matched controls on a second independent neuropsychological test at the screening visit
  • a stable HAART regimen for 3 months with no plans to change the antiretroviral regimen over the study period (confirmed by discussion with a patient's primary provider)
  • the following lab values within 2 weeks prior to entry: hemoglobin > 8.9 g/dl, absolute neutrophil count > 500 cells/mm3, platelet count > 50,000 cells/mm3, ALT < 2.5 X upper limit of normal, alkaline phosphatase < 3 X upper limit of normal, serum creatinine >= 2 X upper limit of normal
  • a negative serum or urine beta-HCG pregnancy test for all women of reproductive potential (have not reached menopause or undergone hysterectomy, oophorectomy, or tubal ligation)
  • neurological examination by a physician revealing no contraindication to a lumbar puncture. If an examination suggests a possible space-occupying brain mass lesion, neuroimaging with CT or MRI must confirm the absence of a mass lesion.

Exclusion Criteria:

  • current or past opportunistic CNS infection (fungal or non-fungal) at study entry
  • current systemic fungal infection
  • current or past use of fluconazole within 30 days of the screening visit
  • history or current clinical evidence of schizophrenia
  • history of chronic neurological disorder such as multiple sclerosis or uncontrolled epilepsy
  • active symptomatic AIDS defining opportunistic infection within 30 days prior to study entry
  • history of abnormal medical illness or current severe affective disorder (e.g., depression with suicidal intention) which in the opinion of the investigators would constitute a safety risk for patients or interfere with the ability of a patient to complete the study
  • treatment with anticoagulants including coumadin, heparin, or low molecular weight heparin which would be a contraindication for the lumbar puncture
  • HIV+ individuals with moderate or severe confounding illnesses
  • prior use of SSRI's within 1 month of screening
  • active substance abuse (illicit drugs and/or controlled medications) or active severe alcohol abuse, evidenced by history intake or urine toxicology at any visit prior to study entry (starting study medication)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01354314

Contacts
Contact: Richard T Moxley, BA 443-799-7241 rmoxley2@jhmi.edu
Contact: Heidi Vornbrock Roosa, BA 443-799-7243 hvornbr1@jhmi.edu

Locations
United States, Maryland
The Johns Hopkins Institute for Clinical and Translational Research, Adult Outpatient Clinical Research Unit Recruiting
Baltimore, Maryland, United States, 21287
Contact: Jared Christopher, RN, BSN     410-955-2760        
Sponsors and Collaborators
Johns Hopkins University
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Ned Sacktor, MD The Johns Hopkins University School of Medicine
  More Information

No publications provided

Responsible Party: Ned Sacktor, Professor of Neurology, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01354314     History of Changes
Other Study ID Numbers: NA_00037283, P30MH075673-05
Study First Received: May 13, 2011
Last Updated: September 18, 2012
Health Authority: United States: Institutional Review Board
United States: National Institutes of Health/NIMH

Keywords provided by Johns Hopkins University:
HIV
Neurocognitive impairment
Memory
Dementia
CSF marker
 Functional assessment
MRS
Magnetic resonance spectroscopy
Arterial spin labeling
SSRI

Additional relevant MeSH terms:
Fluconazole
Paroxetine
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
 Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 22, 2013