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

Primary Purpose

HIV Associated Neurocognitive Disorder

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Fluconazole
Paroxetine
Paroxetine and Fluconazole
Placebo
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Associated Neurocognitive Disorder focused on measuring HIV, Neurocognitive impairment, Memory, Dementia, CSF marker, Functional assessment, MRS, Magnetic resonance spectroscopy, Arterial spin labeling, SSRI

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • The Johns Hopkins Institute for Clinical and Translational Research, Adult Outpatient Clinical Research Unit

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Fluconazole

Paroxetine

Paroxetine and Fluconazole

Placebo

Arm Description

Fluconazole 100 mg every 12 hours orally per day; placebo in place of paroxetine

Paroxetine 20 mg orally once per day; placebo in place of fluconazole

Fluconazole 100 mg every 12 hours orally per day and paroxetine 20 mg every evening orally per day

Placebo in place of both fluconazole and paroxetine

Outcomes

Primary Outcome Measures

Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat
CSF lipid and protein markers of oxidative stress: Change in CSF ceramide (C18:0 levels) between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis).
Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Per Protocol
CSF lipid and protein markers of oxidative stress: Change in CSF ceramide (C18:0 levels) between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis).
Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Intent to Treat
CSF lipid and protein markers of oxidative stress: Change in 3-nitrosylated protein levels between baseline and week 24 for all participants for whom CSF data are available (intent to treat analysis).
Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Per Protocol
CSF lipid and protein markers of oxidative stress: Change in 3-nitrosylated protein levels between baseline and week 24 for participants with 90% or greater adherence to study drug and for whom CSF data are available (per protocol analysis).

Secondary Outcome Measures

Change in CSF sCD14 Between Baseline and Week 24 - Intent to Treat
CSF immune and neuronal injury markers: Change in CSF sCD14 between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis).
Change in CSF sCD14 Between Baseline and Week 24 - Per Protocol
CSF immune and neuronal injury markers: Change in CSF sCD14 between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis).
Change in CSF CD163 Between Baseline and Week 24 - Intent to Treat
CSF immune and neuronal injury markers: Change in CSF CD163 between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis).
Change in CSF CD163 Between Baseline and Week 24 - Per Protocol
CSF immune and neuronal injury markers: Change in CSF CD163 between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis).
Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Intent to Treat
CSF immune and neuronal injury markers: Change in CSF neurofilament protein light chain (NFL) between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis).
Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Per Protocol
CSF immune and neuronal injury markers: Change in CSF neurofilament protein light chain (NFL) between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis).
Change in CSF Neurofilament Protein Heavy Chain (pNFL) Between Baseline and Week 24 - Intent to Treat
CSF immune and neuronal injury markers: Change in CSF neurofilament protein heavy chain (pNFL) between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis).
Change in CSF Neurofilament Protein Heavy Chain (pNFH) Between Baseline and Week 24 - Per Protocol
CSF immune and neuronal injury markers: Change in CSF neurofilament protein heavy chain (pNFH) between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis).
Neurocognitive Performance: Trail Making A - Intent to Treat
Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part A speed of completion (Z scores).
Neurocognitive Performance: Trail Making A - Per Protocol
Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part A speed of completion (Z scores).
Neurocognitive Performance: Trail Making B - Intent to Treat
Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part B speed of completion (Z scores).
Neurocognitive Performance: Trail Making B - Per Protocol
Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part B speed of completion (Z scores).
Neurocognitive Performance: Grooved Pegboard, Dominant - Intent to Treat
Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, dominant hand speed of completion (Z scores).
Neurocognitive Performance: Grooved Pegboard, Dominant - Per Protocol
Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, dominant hand speed of completion (Z scores).
Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Intent to Treat
Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, non-dominant hand speed of completion (Z scores).
Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Per Protocol
Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, non-dominant hand speed of completion (Z scores).
Neurocognitive Performance: CalCAP, Choice - Intent to Treat
Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Choice test, mean reaction time (Z scores).
Neurocognitive Performance: CalCAP, Choice - Per Protocol
Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Choice test, mean reaction time (Z scores).
Neurocognitive Performance: CalCAP, Sequential - Intent to Treat
Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Sequential test, mean reaction time (Z scores).
Neurocognitive Performance: CalCAP, Sequential - Per Protocol
Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Sequential test, mean reaction time (Z scores).
Neurocognitive Performance: Symbol-Digit Test - Intent to Treat
Baseline to Week 24 change in neurocognitive performance as measured by Symbol-Digit Test score, number correct in 120 seconds (Z scores).
Neurocognitive Performance: Symbol-Digit Test - Per Protocol
Baseline to Week 24 change in neurocognitive performance as measured by Symbol-Digit Test score, number correct in 120 seconds (Z scores).
Neurocognitive Performance: Timed Gait - Intent to Treat
Baseline to Week 24 change in neurocognitive performance as measured by Timed Gait, three-trial average time (Z scores).
Neurocognitive Performance: Timed Gait - Per Protocol
Baseline to Week 24 change in neurocognitive performance as measured by Timed Gait, three-trial average time (Z scores).
Neurocognitive Performance: NPZ-8 - Intent to Treat
Baseline to Week 24 change in neurocognitive performance as measured by NPZ-8 scores calculated for all participants who completed the trial with measurable Baseline and Week 24 data for at least 6 of the 8 data points. The data points that comprise the NPZ-8 include timed gait, symbol-digit, grooved pegboard dominant and non-dominant, CalCAP Choice reaction time and Sequential reaction time, Trail-making Test A and B. The baseline to week 24 changes for each test were averaged to get each change in NPZ-8 score.
Neurocognitive Performance: NPZ-8 - Per Protocol
Baseline to Week 24 change in neurocognitive performance as measured by NPZ-8 scores calculated for all participants who completed the trial with measurable Baseline and Week 24 data for at least 6 of the 8 data points. The data points that comprise the NPZ-8 include timed gait, symbol-digit, grooved pegboard dominant and non-dominant, CalCAP Choice reaction time and Sequential reaction time, Trail-making Test A and B. The baseline to week 24 changes for each test were averaged to get each change in NPZ-8 score.
Change in CES-D Score - Intent to Treat
Functional assessment: Change in Center for Epidemiologic Studies Depression Scale (CES-D) score between baseline and week 24 for all participants for whom baseline and follow-up CES-D data are available (intent to treat analysis).
Change in CES-D Score - Per Protocol
Functional assessment: Change in Center for Epidemiologic Studies Depression Scale (CES-D) score between baseline and week 24 for all participants for whom baseline and follow-up CES-D data are available (per protocol).

Full Information

First Posted
May 13, 2011
Last Updated
May 11, 2017
Sponsor
Johns Hopkins University
Collaborators
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT01354314
Brief Title
Study of Paroxetine and Fluconazole for the Treatment of HIV Associated Neurocognitive Disorder
Acronym
ParaFlu
Official Title
Pilot Study of Paroxetine and Fluconazole for the Treatment of HIV Associated Neurocognitive Disorder (HAND)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
November 2010 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Johns Hopkins University
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Associated Neurocognitive Disorder
Keywords
HIV, Neurocognitive impairment, Memory, Dementia, CSF marker, Functional assessment, MRS, Magnetic resonance spectroscopy, Arterial spin labeling, SSRI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Factorial Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fluconazole
Arm Type
Experimental
Arm Description
Fluconazole 100 mg every 12 hours orally per day; placebo in place of paroxetine
Arm Title
Paroxetine
Arm Type
Experimental
Arm Description
Paroxetine 20 mg orally once per day; placebo in place of fluconazole
Arm Title
Paroxetine and Fluconazole
Arm Type
Experimental
Arm Description
Fluconazole 100 mg every 12 hours orally per day and paroxetine 20 mg every evening orally per day
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo in place of both fluconazole and paroxetine
Intervention Type
Drug
Intervention Name(s)
Fluconazole
Intervention Description
One 100 MG capsule taken twice daily, 12 hour dosing
Intervention Type
Drug
Intervention Name(s)
Paroxetine
Intervention Description
Two 10 MG capsules paroxetine once daily in the evening
Intervention Type
Drug
Intervention Name(s)
Paroxetine and Fluconazole
Intervention Description
One capsule 100 MG fluconazole every 12 hours orally per day; Two 10 MG capsules paroxetine orally once daily in the evening
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
One capsule in the morning, three capsules in the evening
Primary Outcome Measure Information:
Title
Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat
Description
CSF lipid and protein markers of oxidative stress: Change in CSF ceramide (C18:0 levels) between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis).
Time Frame
24 Weeks
Title
Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Per Protocol
Description
CSF lipid and protein markers of oxidative stress: Change in CSF ceramide (C18:0 levels) between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis).
Time Frame
24 Weeks
Title
Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Intent to Treat
Description
CSF lipid and protein markers of oxidative stress: Change in 3-nitrosylated protein levels between baseline and week 24 for all participants for whom CSF data are available (intent to treat analysis).
Time Frame
24 Weeks
Title
Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Per Protocol
Description
CSF lipid and protein markers of oxidative stress: Change in 3-nitrosylated protein levels between baseline and week 24 for participants with 90% or greater adherence to study drug and for whom CSF data are available (per protocol analysis).
Time Frame
24 Weeks
Secondary Outcome Measure Information:
Title
Change in CSF sCD14 Between Baseline and Week 24 - Intent to Treat
Description
CSF immune and neuronal injury markers: Change in CSF sCD14 between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis).
Time Frame
24 Weeks
Title
Change in CSF sCD14 Between Baseline and Week 24 - Per Protocol
Description
CSF immune and neuronal injury markers: Change in CSF sCD14 between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis).
Time Frame
24 Weeks
Title
Change in CSF CD163 Between Baseline and Week 24 - Intent to Treat
Description
CSF immune and neuronal injury markers: Change in CSF CD163 between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis).
Time Frame
24 Weeks
Title
Change in CSF CD163 Between Baseline and Week 24 - Per Protocol
Description
CSF immune and neuronal injury markers: Change in CSF CD163 between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis).
Time Frame
24 Weeks
Title
Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Intent to Treat
Description
CSF immune and neuronal injury markers: Change in CSF neurofilament protein light chain (NFL) between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis).
Time Frame
24 Weeks
Title
Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Per Protocol
Description
CSF immune and neuronal injury markers: Change in CSF neurofilament protein light chain (NFL) between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis).
Time Frame
24 Weeks
Title
Change in CSF Neurofilament Protein Heavy Chain (pNFL) Between Baseline and Week 24 - Intent to Treat
Description
CSF immune and neuronal injury markers: Change in CSF neurofilament protein heavy chain (pNFL) between baseline and week 24 for all participants for whom baseline and follow-up CSF data are available (intent to treat analysis).
Time Frame
24 Weeks
Title
Change in CSF Neurofilament Protein Heavy Chain (pNFH) Between Baseline and Week 24 - Per Protocol
Description
CSF immune and neuronal injury markers: Change in CSF neurofilament protein heavy chain (pNFH) between baseline and week 24 for participants with 90% or greater study drug adherence and for whom baseline and follow-up CSF data are available (per protocol analysis).
Time Frame
24 Weeks
Title
Neurocognitive Performance: Trail Making A - Intent to Treat
Description
Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part A speed of completion (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: Trail Making A - Per Protocol
Description
Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part A speed of completion (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: Trail Making B - Intent to Treat
Description
Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part B speed of completion (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: Trail Making B - Per Protocol
Description
Baseline to Week 24 change in neurocognitive performance as measured by the Trail-making test, part B speed of completion (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: Grooved Pegboard, Dominant - Intent to Treat
Description
Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, dominant hand speed of completion (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: Grooved Pegboard, Dominant - Per Protocol
Description
Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, dominant hand speed of completion (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Intent to Treat
Description
Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, non-dominant hand speed of completion (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Per Protocol
Description
Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, non-dominant hand speed of completion (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: CalCAP, Choice - Intent to Treat
Description
Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Choice test, mean reaction time (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: CalCAP, Choice - Per Protocol
Description
Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Choice test, mean reaction time (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: CalCAP, Sequential - Intent to Treat
Description
Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Sequential test, mean reaction time (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: CalCAP, Sequential - Per Protocol
Description
Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Sequential test, mean reaction time (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: Symbol-Digit Test - Intent to Treat
Description
Baseline to Week 24 change in neurocognitive performance as measured by Symbol-Digit Test score, number correct in 120 seconds (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: Symbol-Digit Test - Per Protocol
Description
Baseline to Week 24 change in neurocognitive performance as measured by Symbol-Digit Test score, number correct in 120 seconds (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: Timed Gait - Intent to Treat
Description
Baseline to Week 24 change in neurocognitive performance as measured by Timed Gait, three-trial average time (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: Timed Gait - Per Protocol
Description
Baseline to Week 24 change in neurocognitive performance as measured by Timed Gait, three-trial average time (Z scores).
Time Frame
24 Weeks
Title
Neurocognitive Performance: NPZ-8 - Intent to Treat
Description
Baseline to Week 24 change in neurocognitive performance as measured by NPZ-8 scores calculated for all participants who completed the trial with measurable Baseline and Week 24 data for at least 6 of the 8 data points. The data points that comprise the NPZ-8 include timed gait, symbol-digit, grooved pegboard dominant and non-dominant, CalCAP Choice reaction time and Sequential reaction time, Trail-making Test A and B. The baseline to week 24 changes for each test were averaged to get each change in NPZ-8 score.
Time Frame
24 Weeks
Title
Neurocognitive Performance: NPZ-8 - Per Protocol
Description
Baseline to Week 24 change in neurocognitive performance as measured by NPZ-8 scores calculated for all participants who completed the trial with measurable Baseline and Week 24 data for at least 6 of the 8 data points. The data points that comprise the NPZ-8 include timed gait, symbol-digit, grooved pegboard dominant and non-dominant, CalCAP Choice reaction time and Sequential reaction time, Trail-making Test A and B. The baseline to week 24 changes for each test were averaged to get each change in NPZ-8 score.
Time Frame
24 Weeks
Title
Change in CES-D Score - Intent to Treat
Description
Functional assessment: Change in Center for Epidemiologic Studies Depression Scale (CES-D) score between baseline and week 24 for all participants for whom baseline and follow-up CES-D data are available (intent to treat analysis).
Time Frame
24 Weeks
Title
Change in CES-D Score - Per Protocol
Description
Functional assessment: Change in Center for Epidemiologic Studies Depression Scale (CES-D) score between baseline and week 24 for all participants for whom baseline and follow-up CES-D data are available (per protocol).
Time Frame
24 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ned Sacktor, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Johns Hopkins Institute for Clinical and Translational Research, Adult Outpatient Clinical Research Unit
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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