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

NCT01354314 | Completed Phase 1 Results DMC

• 2 other identifiers: NA_00037283P30MH075673-05
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Associated Neurocognitive Disorder

Keywords

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

Outcome Measures

Primary Outcomes (4)

• 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).

  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).

  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).

  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).

  24 Weeks

Secondary Outcomes (28)

• Change in CSF sCD14 Between Baseline and Week 24 - Intent to Treat

  24 Weeks

• Change in CSF sCD14 Between Baseline and Week 24 - Per Protocol

  24 Weeks

• Change in CSF CD163 Between Baseline and Week 24 - Intent to Treat

  24 Weeks

• Change in CSF CD163 Between Baseline and Week 24 - Per Protocol

  24 Weeks

• Change in CSF Neurofilament Protein Light Chain (NFL) Between Baseline and Week 24 - Intent to Treat

  24 Weeks

Study Arms (4)

Fluconazole

EXPERIMENTAL

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

Drug: Fluconazole

Paroxetine

EXPERIMENTAL

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

Drug: Paroxetine

Paroxetine and Fluconazole

EXPERIMENTAL

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

Drug: Paroxetine and Fluconazole

Placebo

PLACEBO COMPARATOR

Placebo in place of both fluconazole and paroxetine

Drug: Placebo

Interventions

Fluconazole DRUG

One 100 MG capsule taken twice daily, 12 hour dosing

Fluconazole

Paroxetine DRUG

Two 10 MG capsules paroxetine once daily in the evening

Paroxetine

Paroxetine and Fluconazole DRUG

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

Paroxetine and Fluconazole

Placebo DRUG

One capsule in the morning, three capsules in the evening

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

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

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Dementia

Interventions

Fluconazole; Paroxetine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperidines

Results Point of Contact

• Title: Dr. Ned Sacktor
• Organization: The Johns Hopkins University

sacktor@jhmi.edu

410-550-1045

Study Officials

• Ned Sacktor, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: May 13, 2011
• First Posted: May 16, 2011
• Study Start: November 1, 2010
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: June 9, 2017
• Results First Posted: May 12, 2017

Record last verified: 2017-05

Locations

US (1)