HIV Associated Neurocognitive Disorder
Conditions
Keywords
HIV, Neurocognitive impairment, Memory, Dementia, CSF marker, Functional assessment, MRS, Magnetic resonance spectroscopy, Arterial spin labeling, SSRI
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
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
Sponsors
National Institute of Mental Health (NIMH)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
* 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Intent to Treat | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 A - Per Protocol | 24 Weeks | 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 - Per Protocol | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | Baseline to Week 24 change in neurocognitive performance as measured by the Grooved Pegboard test, non-dominant hand speed of completion (Z scores). |
| Change in CSF sCD14 Between Baseline and Week 24 - Intent to Treat | 24 Weeks | 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). |
| Neurocognitive Performance: CalCAP, Choice - Per Protocol | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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). |
| Neurocognitive Performance: CalCAP, Choice - Intent to Treat | 24 Weeks | Baseline to Week 24 change in neurocognitive performance as measured by the CalCAP Choice test, mean reaction time (Z scores). |
| Change in CSF sCD14 Between Baseline and Week 24 - Per Protocol | 24 Weeks | 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 | 24 Weeks | 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 | 24 Weeks | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Paroxetine and Fluconazole Fluconazole 100 mg every 12 hours orally per day and paroxetine 20 mg every evening orally per day
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 | 12 |
| Paroxetine Paroxetine 20 mg orally once per day; placebo in place of fluconazole every 12 hours orally per day
Paroxetine: Two 10 MG capsules paroxetine once daily in the evening | 11 |
| Fluconazole Fluconazole 100 mg every 12 hours orally per day; placebo in place of paroxetine every evening orally per day
Fluconazole: One 100 MG capsule taken twice daily, 12 hour dosing | 11 |
| Placebo Placebos in place of fluconazole and paroxetine
Placebos: One capsule placebo #1 every 12 hours orally per day; Two capsules placebo #2 orally once daily in the evening | 11 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Less than 90% Adherence | 4 | 2 | 6 | 4 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Paroxetine | Fluconazole | Placebo | Total | Paroxetine and Fluconazole |
|---|---|---|---|---|---|
| Absolute CD4 Count | 637.3 Cells per cubic mm STANDARD_DEVIATION 241.7 | 555.2 Cells per cubic mm STANDARD_DEVIATION 282.8 | 510.4 Cells per cubic mm STANDARD_DEVIATION 235.1 | 553.9 Cells per cubic mm STANDARD_DEVIATION 248.2 | 516.1 Cells per cubic mm STANDARD_DEVIATION 244.8 |
| Age, Continuous | 52.00 Years STANDARD_DEVIATION 6.62 | 51.73 Years STANDARD_DEVIATION 5.76 | 48.73 Years STANDARD_DEVIATION 10.23 | 50.56 Years STANDARD_DEVIATION 7.17 | 49.83 Years STANDARD_DEVIATION 5.77 |
| Age, Customized 25 to 34 | 0 Years | 0 Years | 1 Years | 1 Years | 0 Years |
| Age, Customized 35 to 44 | 1 Years | 1 Years | 1 Years | 5 Years | 2 Years |
| Age, Customized 45 to 54 | 7 Years | 7 Years | 5 Years | 27 Years | 8 Years |
| Age, Customized 55 to 64 | 3 Years | 3 Years | 4 Years | 12 Years | 2 Years |
| Education | 12.36 Years Completed STANDARD_DEVIATION 1.8 | 12.91 Years Completed STANDARD_DEVIATION 1.87 | 12.36 Years Completed STANDARD_DEVIATION 2.11 | 12.36 Years Completed STANDARD_DEVIATION 1.94 | 11.83 Years Completed STANDARD_DEVIATION 2.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 11 Participants | 11 Participants | 44 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hepatitis C Infection Status Negative History | 8 participants | 4 participants | 3 participants | 21 participants | 6 participants |
| Hepatitis C Infection Status Positive History | 3 participants | 7 participants | 8 participants | 24 participants | 6 participants |
| Plasma HIV Viral Load Detectable: 100-249 copies/mL | 2 participants | 0 participants | 0 participants | 2 participants | 0 participants |
| Plasma HIV Viral Load Detectable: 250-499 copies/mL | 0 participants | 0 participants | 0 participants | 2 participants | 2 participants |
| Plasma HIV Viral Load Detectable: 50-99 copies/mL | 0 participants | 0 participants | 1 participants | 4 participants | 3 participants |
| Plasma HIV Viral Load Undetectable (<50 copies/mL) | 9 participants | 11 participants | 10 participants | 37 participants | 7 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 10 Participants | 9 Participants | 37 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 1 Participants | 1 Participants | 7 Participants | 2 Participants |
| Sex/Gender, Customized Female | 2 participants | 1 participants | 1 participants | 11 participants | 7 participants |
| Sex/Gender, Customized Male | 9 participants | 10 participants | 9 participants | 32 participants | 4 participants |
| Sex/Gender, Customized Transgender (Male to Female) | 0 participants | 0 participants | 1 participants | 2 participants | 1 participants |
| Years Since HIV Diagnosis | 16.36 Years STANDARD_DEVIATION 7.9 | 15.45 Years STANDARD_DEVIATION 6.76 | 17.36 Years STANDARD_DEVIATION 7.93 | 16.11 Years STANDARD_DEVIATION 7.14 | 15.33 Years STANDARD_DEVIATION 6.77 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 11 / 12 | 10 / 11 | 10 / 11 | 10 / 11 |
| serious Total, serious adverse events | 2 / 12 | 0 / 11 | 3 / 11 | 3 / 11 |
Outcome results
Primary
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
Population: For intention to treat analysis, 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paroxetine and Fluconazole | Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Intent to Treat | 6.392 pi*mm^2 |
| Paroxetine | Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Intent to Treat | 12.235 pi*mm^2 |
| Fluconazole | Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Intent to Treat | 33.767 pi*mm^2 |
| Placebo | Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Intent to Treat | -8.747 pi*mm^2 |
p-value: 0.327Regression, Linear
p-value: 0.178Regression, Linear
p-value: 0.48Regression, Linear
Primary
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
Population: For per protocol analysis, 18 participants (out of the total 22 who completed the trial with 90% or greater study drug adherence) had follow-up CSF for primary outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paroxetine and Fluconazole | Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Per Protocol | 0.712 pi*mm^2 |
| Paroxetine | Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Per Protocol | 0.257 pi*mm^2 |
| Fluconazole | Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Per Protocol | -3.959 pi*mm^2 |
| Placebo | Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Per Protocol | -13.160 pi*mm^2 |
p-value: 0.267Regression, Linear
p-value: 0.368Regression, Linear
p-value: 0.672Regression, Linear
Primary
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
Population: 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paroxetine and Fluconazole | Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat | -30.78 ng/mL |
| Paroxetine | Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat | 4.16 ng/mL |
| Fluconazole | Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat | -12.17 ng/mL |
| Placebo | Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat | -30.56 ng/mL |
p-value: 0.893Regression, Linear
p-value: 0.594Regression, Linear
p-value: 0.712Regression, Linear
Primary
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
Population: For per protocol analysis, 18 participants (out of the 22 who completed the trial with 90% or greater study drug adherence) had follow-up CSF for primary outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paroxetine and Fluconazole | Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Per Protocol | -51.35 ng/mL |
| Paroxetine | Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Per Protocol | 34.11 ng/mL |
| Fluconazole | Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Per Protocol | -65.00 ng/mL |
| Placebo | Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Per Protocol | -52.37 ng/mL |
p-value: 0.673Regression, Linear
p-value: 0.153Regression, Linear
p-value: 0.282Regression, Linear
Secondary
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
Population: Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Change in CES-D Score - Intent to Treat | -1.182 units on a scale | Standard Deviation 6.75 |
| Paroxetine | Change in CES-D Score - Intent to Treat | 1.222 units on a scale | Standard Deviation 13.321 |
| Fluconazole | Change in CES-D Score - Intent to Treat | -1.182 units on a scale | Standard Deviation 2.822 |
| Placebo | Change in CES-D Score - Intent to Treat | 2.600 units on a scale | Standard Deviation 8.618 |
Secondary
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
Population: Per protocol analysis: Includes participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Change in CES-D Score - Per Protocol | 1.667 units on a scale | Standard Deviation 3.327 |
| Paroxetine | Change in CES-D Score - Per Protocol | 6.000 units on a scale | Standard Deviation 16.093 |
| Fluconazole | Change in CES-D Score - Per Protocol | -0.875 units on a scale | Standard Deviation 3.182 |
| Placebo | Change in CES-D Score - Per Protocol | 8.800 units on a scale | Standard Deviation 7.19 |
Secondary
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
Population: 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paroxetine and Fluconazole | Change in CSF CD163 Between Baseline and Week 24 - Intent to Treat | 1.6 ng/mL |
| Paroxetine | Change in CSF CD163 Between Baseline and Week 24 - Intent to Treat | -0.7 ng/mL |
| Fluconazole | Change in CSF CD163 Between Baseline and Week 24 - Intent to Treat | -2.7 ng/mL |
| Placebo | Change in CSF CD163 Between Baseline and Week 24 - Intent to Treat | -3.8 ng/mL |
Secondary
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
Population: For per protocol analysis, 18 participants (out of the 22 who completed the trial with 90% or greater study drug adherence) had follow-up CSF for primary outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paroxetine and Fluconazole | Change in CSF CD163 Between Baseline and Week 24 - Per Protocol | -3.2 ng/mL |
| Paroxetine | Change in CSF CD163 Between Baseline and Week 24 - Per Protocol | -0.7 ng/mL |
| Fluconazole | Change in CSF CD163 Between Baseline and Week 24 - Per Protocol | -7.5 ng/mL |
| Placebo | Change in CSF CD163 Between Baseline and Week 24 - Per Protocol | -1.8 ng/mL |
Secondary
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
Population: For per protocol analysis, 18 participants (out of the 22 who completed the trial with 90% or greater study drug adherence) had follow-up CSF for primary outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paroxetine and Fluconazole | Change in CSF Neurofilament Protein Heavy Chain (pNFH) Between Baseline and Week 24 - Per Protocol | -0.0035 pg/mL |
| Paroxetine | Change in CSF Neurofilament Protein Heavy Chain (pNFH) Between Baseline and Week 24 - Per Protocol | 0.0645 pg/mL |
| Fluconazole | Change in CSF Neurofilament Protein Heavy Chain (pNFH) Between Baseline and Week 24 - Per Protocol | 0.0270 pg/mL |
| Placebo | Change in CSF Neurofilament Protein Heavy Chain (pNFH) Between Baseline and Week 24 - Per Protocol | 0.0395 pg/mL |
Secondary
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
Population: 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paroxetine and Fluconazole | Change in CSF Neurofilament Protein Heavy Chain (pNFL) Between Baseline and Week 24 - Intent to Treat | -0.0080 pg/mL |
| Paroxetine | Change in CSF Neurofilament Protein Heavy Chain (pNFL) Between Baseline and Week 24 - Intent to Treat | 0.0705 pg/mL |
| Fluconazole | Change in CSF Neurofilament Protein Heavy Chain (pNFL) Between Baseline and Week 24 - Intent to Treat | 0.0400 pg/mL |
| Placebo | Change in CSF Neurofilament Protein Heavy Chain (pNFL) Between Baseline and Week 24 - Intent to Treat | 0.0520 pg/mL |
Secondary
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
Population: 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paroxetine and Fluconazole | Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Intent to Treat | 0.0890 pg/mL |
| Paroxetine | Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Intent to Treat | 0.1710 pg/mL |
| Fluconazole | Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Intent to Treat | 0.2030 pg/mL |
| Placebo | Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Intent to Treat | 0.1000 pg/mL |
Secondary
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
Population: For per protocol analysis, 18 participants (out of the 22 who completed the trial with 90% or greater study drug adherence) had follow-up CSF for primary outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paroxetine and Fluconazole | Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Per Protocol | 0.0560 pg/mL |
| Paroxetine | Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Per Protocol | 0.1580 pg/mL |
| Fluconazole | Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Per Protocol | 0.0985 pg/mL |
| Placebo | Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Per Protocol | 0.1375 pg/mL |
Secondary
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
Population: 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paroxetine and Fluconazole | Change in CSF sCD14 Between Baseline and Week 24 - Intent to Treat | -17.7 pg/mL |
| Paroxetine | Change in CSF sCD14 Between Baseline and Week 24 - Intent to Treat | 15.2 pg/mL |
| Fluconazole | Change in CSF sCD14 Between Baseline and Week 24 - Intent to Treat | -16.5 pg/mL |
| Placebo | Change in CSF sCD14 Between Baseline and Week 24 - Intent to Treat | 12.0 pg/mL |
Secondary
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
Population: For per protocol analysis, 18 participants (out of the 22 who completed the trial with 90% or greater study drug adherence) had follow-up CSF for primary outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paroxetine and Fluconazole | Change in CSF sCD14 Between Baseline and Week 24 - Per Protocol | -4.3 pg/mL |
| Paroxetine | Change in CSF sCD14 Between Baseline and Week 24 - Per Protocol | 33.2 pg/mL |
| Fluconazole | Change in CSF sCD14 Between Baseline and Week 24 - Per Protocol | -5.1 pg/mL |
| Placebo | Change in CSF sCD14 Between Baseline and Week 24 - Per Protocol | -18.9 pg/mL |
Secondary
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
Population: Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: CalCAP, Choice - Intent to Treat | 0.152 Z score | Standard Deviation 1.468 |
| Paroxetine | Neurocognitive Performance: CalCAP, Choice - Intent to Treat | -0.570 Z score | Standard Deviation 1.348 |
| Fluconazole | Neurocognitive Performance: CalCAP, Choice - Intent to Treat | 0.871 Z score | Standard Deviation 2.771 |
| Placebo | Neurocognitive Performance: CalCAP, Choice - Intent to Treat | -1.325 Z score | Standard Deviation 1.779 |
Secondary
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
Population: Per protocol analysis: Includes participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: CalCAP, Choice - Per Protocol | -0.440 Z score | Standard Deviation 1.004 |
| Paroxetine | Neurocognitive Performance: CalCAP, Choice - Per Protocol | -1.17 Z score | — |
| Fluconazole | Neurocognitive Performance: CalCAP, Choice - Per Protocol | 1.724 Z score | Standard Deviation 2.711 |
| Placebo | Neurocognitive Performance: CalCAP, Choice - Per Protocol | -0.554 Z score | Standard Deviation 1.751 |
Secondary
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
Population: Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: CalCAP, Sequential - Intent to Treat | 0.272 Z score | Standard Deviation 0.781 |
| Paroxetine | Neurocognitive Performance: CalCAP, Sequential - Intent to Treat | -0.025 Z score | Standard Deviation 0.931 |
| Fluconazole | Neurocognitive Performance: CalCAP, Sequential - Intent to Treat | 0.317 Z score | Standard Deviation 1.534 |
| Placebo | Neurocognitive Performance: CalCAP, Sequential - Intent to Treat | -0.530 Z score | Standard Deviation 0.535 |
Secondary
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
Population: Per protocol analysis: Includes participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: CalCAP, Sequential - Per Protocol | 0.355 Z score | Standard Deviation 0.886 |
| Paroxetine | Neurocognitive Performance: CalCAP, Sequential - Per Protocol | -0.11 Z score | — |
| Fluconazole | Neurocognitive Performance: CalCAP, Sequential - Per Protocol | 0.631 Z score | Standard Deviation 1.464 |
| Placebo | Neurocognitive Performance: CalCAP, Sequential - Per Protocol | -0.394 Z score | Standard Deviation 0.433 |
Secondary
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
Population: Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: Grooved Pegboard, Dominant - Intent to Treat | 0.23 Z score | Standard Deviation 0.92 |
| Paroxetine | Neurocognitive Performance: Grooved Pegboard, Dominant - Intent to Treat | 0.05 Z score | Standard Deviation 1.09 |
| Fluconazole | Neurocognitive Performance: Grooved Pegboard, Dominant - Intent to Treat | 0.57 Z score | Standard Deviation 1.05 |
| Placebo | Neurocognitive Performance: Grooved Pegboard, Dominant - Intent to Treat | -0.01 Z score | Standard Deviation 0.88 |
Secondary
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
Population: Per protocol analysis: Includes all participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: Grooved Pegboard, Dominant - Per Protocol | 0.15 Z score | Standard Deviation 1.1 |
| Paroxetine | Neurocognitive Performance: Grooved Pegboard, Dominant - Per Protocol | -0.67 Z score | Standard Deviation 0.61 |
| Fluconazole | Neurocognitive Performance: Grooved Pegboard, Dominant - Per Protocol | 0.59 Z score | Standard Deviation 1.23 |
| Placebo | Neurocognitive Performance: Grooved Pegboard, Dominant - Per Protocol | -0.14 Z score | Standard Deviation 1.07 |
Secondary
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
Population: Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Intent to Treat | -0.16 Z score | Standard Deviation 1.1 |
| Paroxetine | Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Intent to Treat | -0.11 Z score | Standard Deviation 0.53 |
| Fluconazole | Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Intent to Treat | 0.20 Z score | Standard Deviation 0.85 |
| Placebo | Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Intent to Treat | 0.05 Z score | Standard Deviation 0.85 |
Secondary
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
Population: Per protocol analysis: Includes all participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Per Protocol | -0.17 Z score | Standard Deviation 1.39 |
| Paroxetine | Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Per Protocol | 0.13 Z score | Standard Deviation 0.61 |
| Fluconazole | Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Per Protocol | 0.41 Z score | Standard Deviation 0.94 |
| Placebo | Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Per Protocol | -0.42 Z score | Standard Deviation 0.84 |
Secondary
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
Population: Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: NPZ-8 - Intent to Treat | 0.121 Z score | Standard Deviation 0.538 |
| Paroxetine | Neurocognitive Performance: NPZ-8 - Intent to Treat | -0.165 Z score | Standard Deviation 0.59 |
| Fluconazole | Neurocognitive Performance: NPZ-8 - Intent to Treat | 0.313 Z score | Standard Deviation 0.628 |
| Placebo | Neurocognitive Performance: NPZ-8 - Intent to Treat | -0.191 Z score | Standard Deviation 0.432 |
Secondary
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
Population: Per protocol analysis: Includes participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: NPZ-8 - Per Protocol | -0.005 Z score | Standard Deviation 0.527 |
| Paroxetine | Neurocognitive Performance: NPZ-8 - Per Protocol | -0.298 Z score | Standard Deviation 0.29 |
| Fluconazole | Neurocognitive Performance: NPZ-8 - Per Protocol | 0.575 Z score | Standard Deviation 0.485 |
| Placebo | Neurocognitive Performance: NPZ-8 - Per Protocol | -0.199 Z score | Standard Deviation 0.192 |
Secondary
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
Population: Includes all participants who completed the study with test data available (no data substitution) at the Baseline and Week 24 visits for Intention to Treat analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: Symbol-Digit Test - Intent to Treat | 0.494 Z score | Standard Deviation 0.828 |
| Paroxetine | Neurocognitive Performance: Symbol-Digit Test - Intent to Treat | 0.175 Z score | Standard Deviation 1.183 |
| Fluconazole | Neurocognitive Performance: Symbol-Digit Test - Intent to Treat | 0.050 Z score | Standard Deviation 0.901 |
| Placebo | Neurocognitive Performance: Symbol-Digit Test - Intent to Treat | -0.175 Z score | Standard Deviation 0.677 |
Secondary
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
Population: Per protocol analysis: Includes participants who completed the study per protocol and with test data available (no data substitution) at the Baseline and Week 24 visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: Symbol-Digit Test - Per Protocol | 0.354 Z score | Standard Deviation 0.666 |
| Paroxetine | Neurocognitive Performance: Symbol-Digit Test - Per Protocol | -0.167 Z score | Standard Deviation 1.01 |
| Fluconazole | Neurocognitive Performance: Symbol-Digit Test - Per Protocol | 0.275 Z score | Standard Deviation 0.975 |
| Placebo | Neurocognitive Performance: Symbol-Digit Test - Per Protocol | -0.180 Z score | Standard Deviation 0.903 |
Secondary
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
Population: Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: Timed Gait - Intent to Treat | -0.575 Z score | Standard Deviation 1.038 |
| Paroxetine | Neurocognitive Performance: Timed Gait - Intent to Treat | -0.425 Z score | Standard Deviation 1.135 |
| Fluconazole | Neurocognitive Performance: Timed Gait - Intent to Treat | 0.283 Z score | Standard Deviation 0.869 |
| Placebo | Neurocognitive Performance: Timed Gait - Intent to Treat | -0.148 Z score | Standard Deviation 1.127 |
Secondary
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
Population: Per protocol analysis: Includes participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: Timed Gait - Per Protocol | -0.641 Z score | Standard Deviation 1.141 |
| Paroxetine | Neurocognitive Performance: Timed Gait - Per Protocol | -0.170 Z score | Standard Deviation 1.465 |
| Fluconazole | Neurocognitive Performance: Timed Gait - Per Protocol | 0.574 Z score | Standard Deviation 0.833 |
| Placebo | Neurocognitive Performance: Timed Gait - Per Protocol | -0.584 Z score | Standard Deviation 1.166 |
Secondary
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
Population: Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: Trail Making A - Intent to Treat | 0.045 Z score | Standard Deviation 0.88 |
| Paroxetine | Neurocognitive Performance: Trail Making A - Intent to Treat | 0.067 Z score | Standard Deviation 0.98 |
| Fluconazole | Neurocognitive Performance: Trail Making A - Intent to Treat | 0.000 Z score | Standard Deviation 0.77 |
| Placebo | Neurocognitive Performance: Trail Making A - Intent to Treat | 0.09 Z score | Standard Deviation 0.89 |
Secondary
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
Population: Per protocol analysis: Includes all participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: Trail Making A - Per Protocol | -0.28 Z score | Standard Deviation 0.96 |
| Paroxetine | Neurocognitive Performance: Trail Making A - Per Protocol | 0.17 Z score | Standard Deviation 0.98 |
| Fluconazole | Neurocognitive Performance: Trail Making A - Per Protocol | 0.24 Z score | Standard Deviation 0.58 |
| Placebo | Neurocognitive Performance: Trail Making A - Per Protocol | 0.52 Z score | Standard Deviation 1.01 |
Secondary
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
Population: Includes all participants who completed the study with test data available at the Baseline and Week 24 visits for Intention to Treat analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: Trail Making B - Intent to Treat | 0.47 Z score | Standard Deviation 0.98 |
| Paroxetine | Neurocognitive Performance: Trail Making B - Intent to Treat | -0.71 Z score | Standard Deviation 0.93 |
| Fluconazole | Neurocognitive Performance: Trail Making B - Intent to Treat | 0.51 Z score | Standard Deviation 1.03 |
| Placebo | Neurocognitive Performance: Trail Making B - Intent to Treat | 0.020 Z score | Standard Deviation 0.75 |
Secondary
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
Population: Per protocol analysis: Includes all participants who completed the study per protocol and with test data available at the Baseline and Week 24 visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine and Fluconazole | Neurocognitive Performance: Trail Making B - Per Protocol | 0.63 Z score | Standard Deviation 0.95 |
| Paroxetine | Neurocognitive Performance: Trail Making B - Per Protocol | -0.83 Z score | Standard Deviation 1.48 |
| Fluconazole | Neurocognitive Performance: Trail Making B - Per Protocol | 0.49 Z score | Standard Deviation 0.89 |
| Placebo | Neurocognitive Performance: Trail Making B - Per Protocol | 0.16 Z score | Standard Deviation 0.5 |