Clinical trial NCT02308332: Effect of SwitChing AtriPla to Eviplera on Neurocognitive and Emotional Functioning
Official title: Effect of SwitChing AtriPla to Eviplera on Neurocognitive and Emotional Functioning, ESCAPE Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Neurocognitive Decline
HIV Associated Neurocognitive Disorder
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2014-12-04
Enrollment: 58
Sex: MALE
Minimum age (years): 30
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the effects of switching Atripla to Eviplera on neurocognition measured by neuropsychological testing and functional MRI

Detailed description: Efavirenz, an antiretroviral drug used for the treatment of human immunodeficiency virus 1 (HIV-1) infections, is known for its neurological and psychiatric adverse events. Efavirenz is part of Atripla®, a single tablet regimen (STR), currently the most prescribed antiretroviral drug in the Netherlands. Recently, a new STR has become available, Eviplera® containing a successor of Efavirenz, named Rilpivirin. It has been shown in the phase-3 ECHO and THRIVE studies that Atripla as well as Eviplera have excellent and comparable antiretroviral efficacy in naive HIV-infected patients. Furthermore, data from these studies have shown that Eviplera was associated with fewer neurological and psychiatric adverse events than Atripla over 48 weeks. However, this was only patient reported adverse events, not neuropsychological evaluation. Furthermore, they were treatment naïve for HIV. Moreover, there might be a bias in these kind of switch studies due to the fact that those patients who switch will mostly regard their new combination better than the old one. Contrary, data on the long term impact of Efavirenz on neuropsychological performance and symptoms are conflicting.

Objective: This study aims to investigate the effect of switching from Atripla to Eviplera on neurocognitive performances (neurocognitive testing) and imaging (functional MRI scanning) in virologically suppressed HIV-infected patients.

Eligibility criteria: Inclusion Criteria:

* Male, between 30 and 50 years
* HIV-1 RNA \< 50 copies/mL on screening visit
* on Atripla continuously for ≥6 months preceding the screening visit
* Have a HIV genotype prior to starting cART with Atripla with no known resistance to any of the study agents at any time in the past including, but not limited to RT mutations K65R, K101E/P, E138G/K/Q/R, Y181C/I/V, M184V/I and H221Y
* Negative TPHA or VDRL \< 12 months prior to the screening visit
* no signs of an acute or chronic hepatitis C infection within the past 12 months before screening as defined in the Dutch guideline (Arends et al. Neth J Med 2011)
* No subjective neurocognitive complaints in the preceding 12 months
* willingness to take Eviplera together with food according to the manufacturer's prescriptions.
* Estimated glomerular filtration rate ≥50 mL/min (Cockcroft-Gault formula) on last routine measurement during outpatient clinic
* able to understand and comply to study procedures and to provide written informed consent

Exclusion Criteria:

* Non-native Dutch speakers
* Proven major depression through psychiatric consultation within the past year or on anti-depressant drugs (SSRI or TCA)
* Active or known from medical history past CNS opportunistic infections
* History of proven neurologic disease (e.g. multiple sclerosis, brain tumor, cerebrovascular event, etc)
* Active psychiatric disorders classified according to the DMS V criteria
* History or evidence of alcohol or drug abuse defined according to DSM V criteria
* TSH within normal reference values on last routine measurement during outpatient clinic
* Contraindications for undergoing an MRI; a pacemaker or metallic devices/foreign bodies in situ, proven claustrophobia.

Primary outcomes:
measure: To evaluate the neurocognitive performance as measured by neuropsychological test composite score after 12 weeks in stable HIV-infected patients switched from Atripla to Eviplera compared to a control group of patients on Atripla.
timeFrame: 12 weeks
Secondary outcomes:
measure: to assess the correlation between neurocognitive improvement (neuropsychological evaluation) and functional imaging (fMRI) after switching Atripla to Eviplera
timeFrame: 12 weeks
measure: to evaluate correlation between neurocognitive performance and health related quality of life measured by SF-36 total score after switching from Atripla to Eviplera.
timeFrame: 12 weeks
measure: to assess the emotional functioning measured by HADS total score after switching Atripla to Eviplera by using a paired T-test to calculate differences in mean changes between baseline and end of study
timeFrame: 12 weeks
measure: to assess USER-P (total scores) after switching Atripla to Eviplera
timeFrame: 12 weeks
measure: to assess drug levels of Efavirenz (as a component of Atripla) and Rilpivirin (as a component of Eviplera) in relation to changes in neurocognitive performance and fMRI in both patient groups.
timeFrame: 12 weeks
measure: to evaluate the usefulness of PROMIS instruments in HIV research
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: UMC Utrecht
name: Joop Arends, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: