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

HIV Associated Neurocognitive Disorder Clinical Trial

— ParaFlu  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01354314
• Other study ID #: NA_00037283
• Secondary ID: P30MH075673-05
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 13, 2011
• Last updated: March 31, 2016
• Start date: November 2010
• Est. completion date: March 2016

Study information

• Verified date: March 2016
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: National Institutes of Health/NIMH
• Study type: Interventional

Clinical 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. Fluconazole is an antifungal medication approved by the FDA to treat fungal infections.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Associated Neurocognitive Disorder

Intervention

Drug:
• Fluconazole
One 100 MG capsule taken twice daily, 12 hour dosing
• Paroxetine
Two 10 MG capsules paroxetine once daily in the evening
• 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
• Placebo
One capsule in the morning, three capsules in the evening

Locations

Country	Name	City	State
United States	The Johns Hopkins Institute for Clinical and Translational Research, Adult Outpatient Clinical Research Unit	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CSF lipid and protein markers of oxidative stress	CSF lipid and protein markers of oxidative stress [CSF ceramide and (C18:0 levels) and 3-nitrosylated proteins]	24 Weeks	No
Secondary	Neurocognitive performance	Neurocognitive performance as measured by a standard battery of neuropsychological tests	24 Weeks	No
Secondary	Functional performance	Functional performance as measured by a standard set of subjective and objective functional assessments.	24 Weeks	No
Secondary	Magnetic resonance spectroscopy (MRS) and arterial spin labeling	Analysis of imaging markers as measured by magnetic resonance spectroscopy (MRS) and arterial spin labeling.	24 Weeks	No