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CompletedNCT01354314ParaFluUpdated Jun 9, 2017Results posted

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

A Phase 1/2 interventional study of Fluconazole and Paroxetine in HIV Associated Neurocognitive Disorder, sponsored by Johns Hopkins University. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-06-09.

Sponsored by Johns Hopkins University · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
45
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

Read the 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

02

Conditions studied

  • HIV Associated Neurocognitive Disorder

Keywords

  • HIV
  • Neurocognitive impairment
  • Memory
  • Dementia
  • CSF marker
  • Functional assessment
  • MRS
  • Magnetic resonance spectroscopy
  • Arterial spin labeling
  • SSRI
03

In context

Neurocognitive Disorders

246 studies on the registry are indexed under Neurocognitive Disorders; 88 are open to participants now.

This study's enrollment of 45 is below the median of 72 across 150 interventional studies indexed under Neurocognitive Disorders.

Browse Neurocognitive Disorders studies →

Lead sponsor

Johns Hopkins University is the lead sponsor of 1,783 studies on the registry; 313 are open to participants now.

Of its 203 completed or terminated interventional studies of FDA-regulated products, 140 (69%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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)
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Factorial assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
45 participants (actual)

Study arms

  • Experimental
    Fluconazole

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

    Drug: Fluconazole

  • Experimental
    Paroxetine

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

    Drug: Paroxetine

  • 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

  • Placebo comparator
    Placebo

    Placebo in place of both fluconazole and paroxetine

    Drug: Placebo

Interventions

  • DrugFluconazole

    One 100 MG capsule taken twice daily, 12 hour dosing

  • DrugParoxetine

    Two 10 MG capsules paroxetine once daily in the evening

  • DrugParoxetine and Fluconazole

    One capsule 100 MG fluconazole every 12 hours orally per day; Two 10 MG capsules paroxetine orally once daily in the evening

  • DrugPlacebo

    One capsule in the morning, three capsules in the evening

06

What researchers measure

Primary outcomes

  1. 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).

    Time frame: 24 Weeks

  2. 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).

    Time frame: 24 Weeks

  3. 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).

    Time frame: 24 Weeks

  4. 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).

    Time frame: 24 Weeks

Secondary outcomes

  1. 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).

    Time frame: 24 Weeks

  2. 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).

    Time frame: 24 Weeks

  3. 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).

    Time frame: 24 Weeks

  4. 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).

    Time frame: 24 Weeks

  5. 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).

    Time frame: 24 Weeks

  6. 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).

    Time frame: 24 Weeks

  7. 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).

    Time frame: 24 Weeks

  8. 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).

    Time frame: 24 Weeks

  9. 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).

    Time frame: 24 Weeks

  10. 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).

    Time frame: 24 Weeks

  11. 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).

    Time frame: 24 Weeks

  12. 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).

    Time frame: 24 Weeks

  13. 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).

    Time frame: 24 Weeks

  14. 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).

    Time frame: 24 Weeks

  15. 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).

    Time frame: 24 Weeks

  16. 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).

    Time frame: 24 Weeks

  17. 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).

    Time frame: 24 Weeks

  18. 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).

    Time frame: 24 Weeks

  19. 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).

    Time frame: 24 Weeks

  20. 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).

    Time frame: 24 Weeks

  21. 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).

    Time frame: 24 Weeks

  22. 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).

    Time frame: 24 Weeks

  23. 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).

    Time frame: 24 Weeks

  24. 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).

    Time frame: 24 Weeks

  25. 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.

    Time frame: 24 Weeks

  26. 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.

    Time frame: 24 Weeks

  27. 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).

    Time frame: 24 Weeks

  28. 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).

    Time frame: 24 Weeks

07

Results

Posted May 12, 2017

Participant flow

Participant flow — Overall Study
MilestoneParoxetine and FluconazoleParoxetineFluconazolePlacebo
Started12111111
Completed (itt)1111910
Completed6835
Not completed6386
Withdrew: Lost to follow-up1011
Withdrew: Withdrawal by subject0010
Withdrew: Adverse event0001
Withdrew: Protocol violation1100
Withdrew: Less than 90% adherence4264

Outcome measures

PrimaryChange 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).

Time frame:
24 Weeks
Reported as:
Median · ng/mL
Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat
ng/mLParoxetine and FluconazoleParoxetineFluconazolePlacebo
Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat-30.78 (-68.27 to 24.71)4.16 (-38.76 to 47.95)-12.17 (-56.98 to 9.81)-30.56 (-65.78 to 59.94)
Statistical analysis
  • Paroxetine and Fluconazole vs Placebo · Regression, Linear · p = 0.893
  • Paroxetine vs Placebo · Regression, Linear · p = 0.594
  • Fluconazole vs Placebo · Regression, Linear · p = 0.712
PrimaryChange 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).

Time frame:
24 Weeks
Reported as:
Median · ng/mL
Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Per Protocol
ng/mLParoxetine and FluconazoleParoxetineFluconazolePlacebo
Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Per Protocol-51.35 (-119.66 to 5.95)34.11 (-4.71 to 51.20)-65.00 (-69.00 to -60.99)-52.37 (-87.89 to -7.96)
Statistical analysis
  • Paroxetine and Fluconazole vs Placebo · Regression, Linear · p = 0.673
  • Paroxetine vs Placebo · Regression, Linear · p = 0.153
  • Fluconazole vs Placebo · Regression, Linear · p = 0.282
PrimaryChange 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).

Time frame:
24 Weeks
Reported as:
Median · pi*mm^2
Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Intent to Treat
pi*mm^2Paroxetine and FluconazoleParoxetineFluconazolePlacebo
Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Intent to Treat6.392 (-14.214 to 11.674)12.235 (-23.502 to 30.271)33.767 (-10.912 to 35.853)-8.747 (-21.055 to 4.282)
Statistical analysis
  • Paroxetine and Fluconazole vs Placebo · Regression, Linear · p = 0.327
  • Paroxetine vs Placebo · Regression, Linear · p = 0.178
  • Fluconazole vs Placebo · Regression, Linear · p = 0.480
PrimaryChange 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).

Time frame:
24 Weeks
Reported as:
Median · pi*mm^2
Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Per Protocol
pi*mm^2Paroxetine and FluconazoleParoxetineFluconazolePlacebo
Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Per Protocol0.712 (-17.441 to 10.034)0.257 (-31.676 to 25.563)-3.959 (-22.821 to 14.904)-13.160 (-19.314 to -4.499)
Statistical analysis
  • Paroxetine and Fluconazole vs Placebo · Regression, Linear · p = 0.267
  • Paroxetine vs Placebo · Regression, Linear · p = 0.368
  • Fluconazole vs Placebo · Regression, Linear · p = 0.672
SecondaryChange 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).

Time frame:
24 Weeks
Reported as:
Median · pg/mL
Change in CSF sCD14 Between Baseline and Week 24 - Intent to Treat
pg/mLParoxetine and FluconazoleParoxetineFluconazolePlacebo
Change in CSF sCD14 Between Baseline and Week 24 - Intent to Treat-17.7 (-53.7 to 32.4)15.2 (-19.1 to 72.3)-16.5 (-48.5 to -6.1)12.0 (-53.6 to 21.0)
SecondaryChange 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).

Time frame:
24 Weeks
Reported as:
Median · pg/mL
Change in CSF sCD14 Between Baseline and Week 24 - Per Protocol
pg/mLParoxetine and FluconazoleParoxetineFluconazolePlacebo
Change in CSF sCD14 Between Baseline and Week 24 - Per Protocol-4.3 (-62.0 to 60.3)33.2 (-55.1 to 84.7)-5.1 (-5.6 to -4.5)-18.9 (-51.8 to 12.0)
SecondaryChange 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).

Time frame:
24 Weeks
Reported as:
Median · ng/mL
Change in CSF CD163 Between Baseline and Week 24 - Intent to Treat
ng/mLParoxetine and FluconazoleParoxetineFluconazolePlacebo
Change in CSF CD163 Between Baseline and Week 24 - Intent to Treat1.6 (-3.2 to 3.5)-0.7 (-2.4 to 1.1)-2.7 (-8.1 to 2.6)-3.8 (-5.1 to 1.4)
SecondaryChange 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).

Time frame:
24 Weeks
Reported as:
Median · ng/mL
Change in CSF CD163 Between Baseline and Week 24 - Per Protocol
ng/mLParoxetine and FluconazoleParoxetineFluconazolePlacebo
Change in CSF CD163 Between Baseline and Week 24 - Per Protocol-3.2 (-6.1 to -0.2)-0.7 (-2.5 to 3.9)-7.5 (-9.8 to -5.1)-1.8 (-3.8 to 0.7)
SecondaryChange 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).

Time frame:
24 Weeks
Reported as:
Median · pg/mL
Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Intent to Treat
pg/mLParoxetine and FluconazoleParoxetineFluconazolePlacebo
Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Intent to Treat0.0890 (0.0285 to 0.1855)0.1710 (0.1043 to 0.2733)0.2030 (-0.0270 to 0.2170)0.1000 (-0.0475 to 0.1705)
SecondaryChange 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).

Time frame:
24 Weeks
Reported as:
Median · pg/mL
Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Per Protocol
pg/mLParoxetine and FluconazoleParoxetineFluconazolePlacebo
Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Per Protocol0.0560 (0.0233 to 0.1180)0.1580 (-0.0012 to 0.2588)0.0985 (0.0358 to 0.1613)0.1375 (0.0528 to 0.2223)
SecondaryChange 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).

Time frame:
24 Weeks
Reported as:
Median · pg/mL
Change in CSF Neurofilament Protein Heavy Chain (pNFL) Between Baseline and Week 24 - Intent to Treat
pg/mLParoxetine and FluconazoleParoxetineFluconazolePlacebo
Change in CSF Neurofilament Protein Heavy Chain (pNFL) Between Baseline and Week 24 - Intent to Treat-0.0080 (-0.0275 to 0.0205)0.0705 (0.0338 to 0.0975)0.0400 (0.0290 to 0.1280)0.0520 (0.0345 to 0.0755)
SecondaryChange 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).

Time frame:
24 Weeks
Reported as:
Median · pg/mL
Change in CSF Neurofilament Protein Heavy Chain (pNFH) Between Baseline and Week 24 - Per Protocol
pg/mLParoxetine and FluconazoleParoxetineFluconazolePlacebo
Change in CSF Neurofilament Protein Heavy Chain (pNFH) Between Baseline and Week 24 - Per Protocol-0.0035 (-0.0208 to 0.0303)0.0645 (0.0133 to 0.0888)0.0270 (0.0205 to 0.0335)0.0395 (0.0130 to 0.0618)
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: Trail Making A - Intent to Treat
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: Trail Making A - Intent to Treat0.045 ± 0.880.067 ± 0.980.000 ± 0.770.09 ± 0.89
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: Trail Making A - Per Protocol
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: Trail Making A - Per Protocol-0.28 ± 0.960.17 ± 0.980.24 ± 0.580.52 ± 1.01
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: Trail Making B - Intent to Treat
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: Trail Making B - Intent to Treat0.47 ± 0.98-0.71 ± 0.930.51 ± 1.030.020 ± 0.75
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: Trail Making B - Per Protocol
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: Trail Making B - Per Protocol0.63 ± 0.95-0.83 ± 1.480.49 ± 0.890.16 ± 0.50
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: Grooved Pegboard, Dominant - Intent to Treat
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: Grooved Pegboard, Dominant - Intent to Treat0.23 ± 0.920.05 ± 1.090.57 ± 1.05-0.01 ± 0.88
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: Grooved Pegboard, Dominant - Per Protocol
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: Grooved Pegboard, Dominant - Per Protocol0.15 ± 1.10-0.67 ± 0.610.59 ± 1.23-0.14 ± 1.07
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Intent to Treat
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Intent to Treat-0.16 ± 1.10-0.11 ± 0.530.20 ± 0.850.05 ± 0.85
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Per Protocol
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Per Protocol-0.17 ± 1.390.13 ± 0.610.41 ± 0.94-0.42 ± 0.84
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: CalCAP, Choice - Intent to Treat
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: CalCAP, Choice - Intent to Treat0.152 ± 1.468-0.570 ± 1.3480.871 ± 2.771-1.325 ± 1.779
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: CalCAP, Choice - Per Protocol
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: CalCAP, Choice - Per Protocol-0.440 ± 1.004-1.17 ± NA1.724 ± 2.711-0.554 ± 1.751
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: CalCAP, Sequential - Intent to Treat
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: CalCAP, Sequential - Intent to Treat0.272 ± 0.781-0.025 ± 0.9310.317 ± 1.534-0.530 ± 0.535
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: CalCAP, Sequential - Per Protocol
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: CalCAP, Sequential - Per Protocol0.355 ± 0.886-0.11 ± NA0.631 ± 1.464-0.394 ± 0.433
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: Symbol-Digit Test - Intent to Treat
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: Symbol-Digit Test - Intent to Treat0.494 ± 0.8280.175 ± 1.1830.050 ± 0.901-0.175 ± 0.677
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: Symbol-Digit Test - Per Protocol
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: Symbol-Digit Test - Per Protocol0.354 ± 0.666-0.167 ± 1.0100.275 ± 0.975-0.180 ± 0.903
SecondaryNeurocognitive 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).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: Timed Gait - Intent to Treat
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: Timed Gait - Intent to Treat-0.575 ± 1.038-0.425 ± 1.1350.283 ± 0.869-0.148 ± 1.127
SecondaryNeurocognitive Performance: Timed Gait - Per Protocol

Baseline to Week 24 change in neurocognitive performance as measured by Timed Gait, three-trial average time (Z scores).

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: Timed Gait - Per Protocol
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: Timed Gait - Per Protocol-0.641 ± 1.141-0.170 ± 1.4650.574 ± 0.833-0.584 ± 1.166
SecondaryNeurocognitive 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.

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: NPZ-8 - Intent to Treat
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: NPZ-8 - Intent to Treat0.121 ± 0.538-0.165 ± 0.5900.313 ± 0.628-0.191 ± 0.432
SecondaryNeurocognitive 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.

Time frame:
24 Weeks
Reported as:
Mean · Z score
Neurocognitive Performance: NPZ-8 - Per Protocol
Z scoreParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Neurocognitive Performance: NPZ-8 - Per Protocol-0.005 ± 0.527-0.298 ± 0.2900.575 ± 0.485-0.199 ± 0.192
SecondaryChange 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).

Time frame:
24 Weeks
Reported as:
Mean · units on a scale
Change in CES-D Score - Intent to Treat
units on a scaleParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Change in CES-D Score - Intent to Treat-1.182 ± 6.7501.222 ± 13.321-1.182 ± 2.8222.600 ± 8.618
SecondaryChange 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).

Time frame:
24 Weeks
Reported as:
Mean · units on a scale
Change in CES-D Score - Per Protocol
units on a scaleParoxetine and FluconazoleFluconazoleParoxetinePlacebo
Change in CES-D Score - Per Protocol1.667 ± 3.3276.000 ± 16.093-0.875 ± 3.1828.800 ± 7.190

Adverse events

Collected over Adverse event data were collected during the 24 week clinical trial period for each subject, and if pertinent, during the follow-up period, which was at least 14 days and up to 60 days after discontinuation of the intervention. When applicable, some adverse event data were collected between the screening visit and baseline visit (e.g., safety data pertaining to the lumbar puncture procedure).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Paroxetine and Fluconazole0/12 (0%)2/12 (16.7%)11/12 (91.7%)
Paroxetine0/11 (0%)0/11 (0%)10/11 (90.9%)
Fluconazole0/11 (0%)3/11 (27.3%)10/11 (90.9%)
Placebo0/11 (0%)3/11 (27.3%)10/11 (90.9%)
Most frequent serious events
Most frequent serious events
EventParoxetine and FluconazoleParoxetineFluconazolePlacebo
Surgery, knee replacementSurgical and medical procedures1/120/110/111/11
Heroin abuse, relapseInjury, poisoning and procedural complications0/120/111/111/11
Small bowel obstructionGastrointestinal disorders0/120/110/111/11
Glucose, non-fasting, highEndocrine disorders0/120/111/110/11
Depression, acutePsychiatric disorders0/120/111/110/11
Surgery, neckSurgical and medical procedures1/120/110/110/11
Most frequent other events
Showing 10 of 58
Most frequent other events
EventParoxetine and FluconazoleParoxetineFluconazolePlacebo
DiarrheaGastrointestinal disorders5/121/111/112/11
NauseaGastrointestinal disorders4/121/114/111/11
Sexual dysfunctionReproductive system and breast disorders0/124/111/110/11
Bilirubin, total, highHepatobiliary disorders0/122/113/111/11
Blood urea nitrogen (BUN), highMetabolism and nutrition disorders3/120/111/113/11
Glucose, blood, highEndocrine disorders0/120/113/111/11
Dry mouthGeneral disorders3/120/112/110/11
Depressed moodPsychiatric disorders0/120/112/110/11
Headache, non-specificGeneral disorders1/122/111/110/11
InsomniaGeneral disorders0/122/111/110/11

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Paroxetine and FluconazoleParoxetineFluconazolePlaceboTotal
Mean49.83 ± 5.7752.00 ± 6.6251.73 ± 5.7648.73 ± 10.2350.56 ± 7.17
Age, Customized
Age, Customized(Years)Paroxetine and FluconazoleParoxetineFluconazolePlaceboTotal
25 to 3400011
35 to 4421115
45 to 54877527
55 to 64233412
Sex/Gender, Customized
Sex/Gender, Customized(participants)Paroxetine and FluconazoleParoxetineFluconazolePlaceboTotal
Male4910932
Female721111
Transgender (Male to Female)10012
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Paroxetine and FluconazoleParoxetineFluconazolePlaceboTotal
Hispanic or Latino10001
Not Hispanic or Latino1111111144
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Paroxetine and FluconazoleParoxetineFluconazolePlaceboTotal
American Indian or Alaska Native00000
Asian00011
Native Hawaiian or Other Pacific Islander00000
Black or African American10810937
White23117
More than one race00000
Unknown or Not Reported00000
Education
Education(Years Completed)Paroxetine and FluconazoleParoxetineFluconazolePlaceboTotal
Mean11.83 ± 2.0812.36 ± 1.8012.91 ± 1.8712.36 ± 2.1112.36 ± 1.94
Years Since HIV Diagnosis
Years Since HIV Diagnosis(Years)Paroxetine and FluconazoleParoxetineFluconazolePlaceboTotal
Mean15.33 ± 6.7716.36 ± 7.9015.45 ± 6.7617.36 ± 7.9316.11 ± 7.14
Absolute CD4 Count
Absolute CD4 Count(Cells per cubic mm)Paroxetine and FluconazoleParoxetineFluconazolePlaceboTotal
Mean516.1 ± 244.8637.3 ± 241.7555.2 ± 282.8510.4 ± 235.1553.9 ± 248.2

2 further baseline measures are reported on the registry.

08

Study locations

1 site
  • The Johns Hopkins Institute for Clinical and Translational Research, Adult Outpatient Clinical Research Unit
    Baltimore, Maryland 21287, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 9, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01354314
Lead sponsor
Johns Hopkins University
Collaborators
National Institute of Mental Health (NIMH)
Responsible party
Ned Sacktor (Professor of Neurology, Johns Hopkins University) — Principal investigator
First posted
May 16, 2011
Start date
Nov 2010
Primary completion
Mar 2016
Completion
Mar 2016
Results posted
May 12, 2017
Last update
Jun 9, 2017

Study contacts

Ned Sacktor, MD
principal investigator · Johns Hopkins University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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