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

NCT ID: NCT01354314

Last Updated: 2017-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2016-03-31

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

Conditions

HIV Associated Neurocognitive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Fluconazole

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

Group Type: EXPERIMENTAL

Fluconazole

Intervention Type: DRUG

One 100 MG capsule taken twice daily, 12 hour dosing

Paroxetine

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

Group Type: EXPERIMENTAL

Paroxetine

Intervention Type: DRUG

Two 10 MG capsules paroxetine once daily in the evening

Paroxetine and Fluconazole

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

Group Type: EXPERIMENTAL

Paroxetine and Fluconazole

Intervention Type: DRUG

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

Placebo

Placebo in place of both fluconazole and paroxetine

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One capsule in the morning, three capsules in the evening

Interventions

Fluconazole

One 100 MG capsule taken twice daily, 12 hour dosing

Intervention Type: DRUG

Paroxetine

Two 10 MG capsules paroxetine once daily in the evening

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo

One capsule in the morning, three capsules in the evening

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• HIV+ based on ELISA and confirmed by either Western blot or plasma HIV RNA
• capable of providing informed consent
• age range: 18-65 years
• presence of neuropsychological testing impairment as defined by performance at least 1.0 standard deviation below age-matched and education-matched controls on three or more independent neuropsychological tests at the screening visit, or performance at least 2.0 standard deviations below age-matched and education-matched controls on one independent neuropsychological test and at least 1.0 standard deviation below age-matched and education-matched controls on a second independent neuropsychological test at the screening visit
• a stable HAART regimen for 3 months with no plans to change the antiretroviral regimen over the study period (confirmed by discussion with a patient's primary provider)
• the following lab values within 2 weeks prior to entry: hemoglobin > 8.9 g/dl, absolute neutrophil count > 500 cells/mm3, platelet count > 50,000 cells/mm3, ALT < 2.5 X upper limit of normal, alkaline phosphatase < 3 X upper limit of normal, serum creatinine >= 2 X upper limit of normal
• a negative serum or urine beta-HCG pregnancy test for all women of reproductive potential (have not reached menopause or undergone hysterectomy, oophorectomy, or tubal ligation)
• neurological examination by a physician revealing no contraindication to a lumbar puncture. If an examination suggests a possible space-occupying brain mass lesion, neuroimaging with CT or MRI must confirm the absence of a mass lesion.

Exclusion Criteria

• current or past opportunistic CNS infection (fungal or non-fungal) at study entry
• current systemic fungal infection
• current or past use of fluconazole within 30 days of the screening visit
• history or current clinical evidence of schizophrenia
• history of chronic neurological disorder such as multiple sclerosis or uncontrolled epilepsy
• active symptomatic AIDS defining opportunistic infection within 30 days prior to study entry
• history of abnormal medical illness or current severe affective disorder (e.g., depression with suicidal intention) which in the opinion of the investigators would constitute a safety risk for patients or interfere with the ability of a patient to complete the study
• treatment with anticoagulants including coumadin, heparin, or low molecular weight heparin which would be a contraindication for the lumbar puncture
• HIV+ individuals with moderate or severe confounding illnesses
• prior use of SSRI's within 1 month of screening
• active substance abuse (illicit drugs and/or controlled medications) or active severe alcohol abuse, evidenced by history intake or urine toxicology at any visit prior to study entry (starting study medication)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Ned Sacktor

Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ned Sacktor, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

P30MH075673-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NA_00037283

Identifier Type: -

Identifier Source: org_study_id