Conditions: HIV Associated Neurocognitive Disorder
Keywords: HIV Neurocognitive impairment Memory Dementia CSF marker Functional assessment MRS Magnetic resonance spectroscopy Arterial spin labeling SSRI
Allocation: RANDOMIZED | Intervention model: FACTORIAL
Enrollment: 45
Healthy volunteers: no

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

Arms:
arm 1: Fluconazole 100 mg every 12 hours orally per day; placebo in place of paroxetine arm 2: Paroxetine 20 mg orally once per day; placebo in place of fluconazole arm 3: Fluconazole 100 mg every 12 hours orally per day and paroxetine 20 mg every evening orally per day arm 4: Placebo in place of both fluconazole and paroxetine

Interventions: intervention 1: Fluconazole intervention 2: Paroxetine intervention 3: Paroxetine and Fluconazole intervention 4: Placebo
Intervention descriptions: intervention 1: One 100 MG capsule taken twice daily, 12 hour dosing intervention 2: Two 10 MG capsules paroxetine once daily in the evening intervention 3: One capsule 100 MG fluconazole every 12 hours orally per day; Two 10 MG capsules paroxetine orally once daily in the evening intervention 4: One capsule in the morning, three capsules in the evening

Protocol document: