HIV Associated Neurocognitive DisorderPhase 1/2ParaFluNCT01354314

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

A Phase 1/2 study testing Fluconazole, Paroxetine and Paroxetine and Fluconazole in people with HIV Associated Neurocognitive Disorder, run by Johns Hopkins University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: HIV Associated Neurocognitive Disorder
What is being tested?: Fluconazole, Paroxetine and Paroxetine and Fluconazole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 45 participants
Where: 1 siteUnited States
Study dates: Nov 2010to Mar 2016
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

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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)

Trial locations and contacts

1 site in 1 country.

United States1 site

The Johns Hopkins Institute for Clinical and Translational Research, Adult Outpatient Clinical Research Unit
Baltimore, Maryland, 21287

Other trials in United States

About this study

Official title: Pilot Study of Paroxetine and Fluconazole for the Treatment of HIV Associated Neurocognitive Disorder (HAND)

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:

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

Conditions: HIV Associated Neurocognitive Disorder
Being tested: Fluconazole, Paroxetine, Paroxetine and Fluconazole, Placebo
Keywords: HIV, Neurocognitive impairment, Memory, Dementia, CSF marker, Functional assessment, MRS, Magnetic resonance spectroscopy, Arterial spin labeling, SSRI
Medical subject headings: Dementia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FluconazoleDrug
One 100 MG capsule taken twice daily, 12 hour dosing
ParoxetineDrug
Two 10 MG capsules paroxetine once daily in the evening
Paroxetine and FluconazoleDrug
One capsule 100 MG fluconazole every 12 hours orally per day; Two 10 MG capsules paroxetine orally once daily in the evening
PlaceboDrug
One capsule in the morning, three capsules in the evening

Study groups in NCT01354314
Study group	Role	What they receive
Fluconazole	Experimental	Fluconazole 100 mg every 12 hours orally per day; placebo in place of paroxetine Receives: Drug: Fluconazole
Paroxetine	Experimental	Paroxetine 20 mg orally once per day; placebo in place of fluconazole Receives: Drug: Paroxetine
Paroxetine and Fluconazole	Experimental	Fluconazole 100 mg every 12 hours orally per day and paroxetine 20 mg every evening orally per day Receives: Drug: Paroxetine and Fluconazole
Placebo	Placebo comparator	Placebo in place of both fluconazole and paroxetine Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks

Secondary outcomes (28)

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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks
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.
Measured: 24 Weeks
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.
Measured: 24 Weeks
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).
Measured: 24 Weeks
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).
Measured: 24 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2010Mar 2016

First posted16 May 2011 (estimated)
Study startNov 2010
Primary completionMar 2016
Study completionMar 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HIV Associated Neurocognitive DisorderStudies of the same condition, open and under way.
More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 45 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01354314
Sponsor's protocol ID: NA_00037283
Other IDs: P30MH075673-05
Acronym: ParaFlu
Status last verified: May 2017
First submitted: 13 May 2011
Last updated: 9 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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SV2A & TSPO PET Imaging Measures to Reveal Mechanisms of HIV Neuropathogenesis During Antiretroviral Therapy
HIV Associated Neurocognitive Disorder, HIV Dementia
RecruitingObservational study
Thinking and Memory Problems in People With HIV
HIV Positive

All HIV Associated Neurocognitive Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pilot Study of Paroxetine and Fluconazole for the Treatment of HIV Associated Neurocognitive Disorder (HAND)
ClinicalTrials.gov ID: NCT01354314
Acronym / sponsor ID: ParaFlu / NA_00037283
Conditions: HIV Associated Neurocognitive Disorder
Keywords: HIV, Neurocognitive impairment, Memory, Dementia, CSF marker, Functional assessment, MRS, Magnetic resonance spectroscopy
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 45 participants (actual)
Lead sponsor: Johns Hopkins UniversityUniversity, hospital or other
Collaborators: National Institute of Mental Health (NIMH)
Study start: Nov 2010
Primary completion: Mar 2016 (actual)
Study completion: Mar 2016 (actual)
First posted: 16 May 2011 (estimated)
Results: Posted 12 May 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Secondary Aims:

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 4

Arm	Type	Receives
Fluconazole	Experimental	Drug: FluconazoleFluconazole 100 mg every 12 hours orally per day; placebo in place of paroxetine
Paroxetine	Experimental	Drug: ParoxetineParoxetine 20 mg orally once per day; placebo in place of fluconazole
Paroxetine and Fluconazole	Experimental	Drug: Paroxetine and FluconazoleFluconazole 100 mg every 12 hours orally per day and paroxetine 20 mg every evening orally per day
Placebo	Placebo comparator	Drug: PlaceboPlacebo in place of both fluconazole and paroxetine

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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)

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FluconazoleOne 100 MG capsule taken twice daily, 12 hour dosing	Drug	Fluconazole
ParoxetineTwo 10 MG capsules paroxetine once daily in the evening	Drug	Paroxetine
Paroxetine and FluconazoleOne capsule 100 MG fluconazole every 12 hours orally per day; Two 10 MG capsules paroxetine orally once daily in the evening	Drug	Paroxetine and Fluconazole
PlaceboOne capsule in the morning, three capsules in the evening	Drug	Placebo

Primary outcome

Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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).

28 secondary outcomes

Change in CSF sCD14 Between Baseline and Week 24 - Intent to Treat
Time frame: 24 Weeks
Change in CSF sCD14 Between Baseline and Week 24 - Per Protocol
Time frame: 24 Weeks
Change in CSF CD163 Between Baseline and Week 24 - Intent to Treat
Time frame: 24 Weeks
Change in CSF CD163 Between Baseline and Week 24 - Per Protocol
Time frame: 24 Weeks
Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Intent to Treat
Time frame: 24 Weeks
Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Per Protocol
Time frame: 24 Weeks
Change in CSF Neurofilament Protein Heavy Chain (pNFL) Between Baseline and Week 24 - Intent to Treat
Time frame: 24 Weeks
Change in CSF Neurofilament Protein Heavy Chain (pNFH) Between Baseline and Week 24 - Per Protocol
Time frame: 24 Weeks
Neurocognitive Performance: Trail Making A - Intent to Treat
Time frame: 24 Weeks
Neurocognitive Performance: Trail Making A - Per Protocol
Time frame: 24 Weeks
Neurocognitive Performance: Trail Making B - Intent to Treat
Time frame: 24 Weeks
Neurocognitive Performance: Trail Making B - Per Protocol
Time frame: 24 Weeks
Neurocognitive Performance: Grooved Pegboard, Dominant - Intent to Treat
Time frame: 24 Weeks
Neurocognitive Performance: Grooved Pegboard, Dominant - Per Protocol
Time frame: 24 Weeks
Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Intent to Treat
Time frame: 24 Weeks
Neurocognitive Performance: Grooved Pegboard, Non-Dominant - Per Protocol
Time frame: 24 Weeks
Neurocognitive Performance: CalCAP, Choice - Intent to Treat
Time frame: 24 Weeks
Neurocognitive Performance: CalCAP, Choice - Per Protocol
Time frame: 24 Weeks
Neurocognitive Performance: CalCAP, Sequential - Intent to Treat
Time frame: 24 Weeks
Neurocognitive Performance: CalCAP, Sequential - Per Protocol
Time frame: 24 Weeks
Neurocognitive Performance: Symbol-Digit Test - Intent to Treat
Time frame: 24 Weeks
Neurocognitive Performance: Symbol-Digit Test - Per Protocol
Time frame: 24 Weeks
Neurocognitive Performance: Timed Gait - Intent to Treat
Time frame: 24 Weeks
Neurocognitive Performance: Timed Gait - Per Protocol
Time frame: 24 Weeks
Neurocognitive Performance: NPZ-8 - Intent to Treat
Time frame: 24 Weeks
Neurocognitive Performance: NPZ-8 - Per Protocol
Time frame: 24 Weeks
Change in CES-D Score - Intent to Treat
Time frame: 24 Weeks
Change in CES-D Score - Per Protocol
Time frame: 24 Weeks

Results and safety

Results posted to the registry on 12 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Paroxetine and Fluconazole	12	6
Paroxetine	11	8
Fluconazole	11	3
Placebo	11	5

Primary outcome: Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat

Time frame: 24 Weeks. Median (Inter-Quartile Range). Unit: ng/mL

Measure	Paroxetine and Fluconazole n = 11	Paroxetine n = 8	Fluconazole n = 5	Placebo n = 7
Value	-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)

Paroxetine and Fluconazole vs Placebo: p = 0.893, Regression, Linear
Paroxetine vs Placebo: p = 0.594, Regression, Linear
Fluconazole vs Placebo: p = 0.712, Regression, Linear

Population analysed: 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures.

Primary outcome: Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Per Protocol

Time frame: 24 Weeks. Median (Inter-Quartile Range). Unit: ng/mL

Measure	Paroxetine and Fluconazole n = 6	Paroxetine n = 6	Fluconazole n = 2	Placebo n = 4
Value	-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)

Paroxetine and Fluconazole vs Placebo: p = 0.673, Regression, Linear
Paroxetine vs Placebo: p = 0.153, Regression, Linear
Fluconazole vs Placebo: p = 0.282, Regression, Linear

Population analysed: 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.

Primary outcome: Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Intent to Treat

Time frame: 24 Weeks. Median (Inter-Quartile Range). Unit: pi*mm^2

Measure	Paroxetine and Fluconazole n = 11	Paroxetine n = 8	Fluconazole n = 5	Placebo n = 7
Value	6.392 (-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)

Paroxetine and Fluconazole vs Placebo: p = 0.327, Regression, Linear
Paroxetine vs Placebo: p = 0.178, Regression, Linear
Fluconazole vs Placebo: p = 0.480, Regression, Linear

Population analysed: For intention to treat analysis, 31 participants, out of the total 45 enrolled, completed the trial with follow-up CSF primary outcome measures.

Primary outcome: Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Per Protocol

Time frame: 24 Weeks. Median (Inter-Quartile Range). Unit: pi*mm^2

Measure	Paroxetine and Fluconazole n = 6	Paroxetine n = 6	Fluconazole n = 2	Placebo n = 4
Value	0.712 (-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)

Paroxetine and Fluconazole vs Placebo: p = 0.267, Regression, Linear
Paroxetine vs Placebo: p = 0.368, Regression, Linear
Fluconazole vs Placebo: p = 0.672, Regression, Linear

Population analysed: 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.

28 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Paroxetine and Fluconazole	2 of 12 (16.7%)	11 of 12 (91.7%)	0 of 12
Paroxetine	0 of 11 (0%)	10 of 11 (90.9%)	0 of 11
Fluconazole	3 of 11 (27.3%)	10 of 11 (90.9%)	0 of 11
Placebo	3 of 11 (27.3%)	10 of 11 (90.9%)	0 of 11

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ned Sacktor, MD principal investigator

Johns Hopkins University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Fluconazole, Paroxetine and Paroxetine and Fluconazole in people with HIV Associated Neurocognitive Disorder, run by Johns Hopkins University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat (time frame: 24 Weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01354314.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2017.

Trial summary

Key requirements

Who may be able to join

Who cannot join

Trial locations and contacts

About this study

What participants receive

What is being measured

Timeline

Resources

More details

Study at a glance

Clinical summary

Study design

Who may qualify

Key inclusion criteria (8 listed)

Key exclusion criteria (11 listed)

Interventions

Primary outcome

Results and safety

Participant flow

Primary outcome: Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat

Primary outcome: Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Per Protocol

Primary outcome: Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Intent to Treat

Primary outcome: Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Per Protocol

Adverse events

Research links

Related trials for HIV Associated Neurocognitive Disorder

SV2A & TSPO PET Imaging Measures to Reveal Mechanisms of HIV Neuropathogenesis During Antiretroviral Therapy

Thinking and Memory Problems in People With HIV

Referral and contact

Questions about this trial

Participant flow

Primary outcome: Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Intent to Treat

Primary outcome: Change in CSF Ceramide Between Baseline and Week 24 (C18:0 Levels) - Per Protocol

Primary outcome: Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Intent to Treat

Primary outcome: Change in CSF 3-nitrosylated Protein Levels Between Baseline and Week 24 - Per Protocol

Adverse events