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Neurocognitive DeclinePhase 4ESCAPENCT02308332

Effect of SwitChing AtriPla to Eviplera on Neurocognitive and Emotional Functioning

A Phase 4 study testing Eviplera in people with Neurocognitive Decline and HIV Associated Neurocognitive Disorder, run by UMC Utrecht at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will evaluate the effects of switching Atripla to Eviplera on neurocognition measured by neuropsychological testing and functional MRI Read more about this study

Who is it for?
Ages 30 to 50 years, men onlyHealthy volunteers can take part
What is being tested?
Eviplera
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
1 siteNetherlands
Study dates
Feb 2015to Jun 2017
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 50 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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)
Show all 10Show fewer
  • 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • UMC Utrecht

    Utrecht

Other trials in Netherlands

About this study

Official title: Effect of SwitChing AtriPla to Eviplera on Neurocognitive and Emotional Functioning, ESCAPE Study

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

Read the 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.

Being tested
Eviplera

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EvipleraDrug

    Also called emtricitabine/rilpivirine/tenofovir

    switch from Atripla to emtricitabine/rilpivirine/tenofovir (Eviplera)

Study groups in NCT02308332
Study groupRoleWhat they receive
InterventionActive comparatorpatients switching from Atripla to Eviplera
Receives: Drug: Eviplera
ControlNo interventionpatients remaining on Atripla

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Patients will undergo a neuropsychological test battery where multiple standardized test will be undertaken to assess 7 different domains; Verbal Fluency, Executive Functioning, Speed of Information Processing, Learning, Memory, Attention/Working Memory, Motor skills. Raw scores can be calculated per domain and as a composite score. Differences in mean changes in composite score between baseline and end of study will be assessed with a paired T-test. A p-value <0.05 will be considered statistically significant. Within-arm changes will be assessed using Wilcoxon signed rank tests, and between-group comparisons will be evaluated with Wilcoxon rank sum tests. Multivariate analyses will be performed to analyse differences in the primary endpoints between the study groups.

    Measured: 12 weeks

Secondary outcomes (6)

  1. to assess the correlation between neurocognitive improvement (neuropsychological evaluation) and functional imaging (fMRI) after switching Atripla to Eviplera

    The aim is to investigate if there is a correlation between improvement on neuropsychological test scores after 12 weeks of Eviplera therapy, and changes on fMRI after 12 weeks of Eviplera therapy. If there is a correlation, that means fMRI could be used to evaluate neurocognitive decline. Basically, we will asses if there is a correlation between ∆neuropsychological score and ∆fMRI-score. Because this is ordinal data, we will use a Spearman rank-order correlation to calculate a correlation-coefficient.

    Measured: 12 weeks

  2. to evaluate correlation between neurocognitive performance and health related quality of life measured by SF-36 total score after switching from Atripla to Eviplera.

    The aim is if an improvement in neuropsychological test scores after 12 weeks of Eviplera therapy is correlated with an improvement of quality of life. Basically, we will assess if there is a correlation between ∆neuropsychological score and ∆SF-36 total score. Because this is ordinal data, we will use a Spearman rank-order correlation to calculate a correlation-coefficient.

    Measured: 12 weeks

  3. 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

    Measured: 12 weeks

  4. to assess USER-P (total scores) after switching Atripla to Eviplera

    Measured: 12 weeks

  5. 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.

    With this study, we want to investigate the effect of switching Efavirenz (as a component of Atripla) to Rilpivirine (as a component of Eviplera) on neurocognition. Our hypothesis is that neurocognition (as measured by neuropsychological testing scores) will improve when switching from Efavirenz (as a component of Atripla). If that is the case, hypothetically a lower or higher drug level of Efavirenz (as a component of Atripla) could have an effect on neurocognition (as measured by neuropsychological test scores). We will assess the correlation between drug level of Efavirenz or Rilpivirine and changes in neurocognitive function as measured by neuropsychological testing, and fMRI changes by regression analyses using drug levels as an independent variable and neuropsychological test scores as a dependent variable.

    Measured: 12 weeks

  6. to evaluate the usefulness of PROMIS instruments in HIV research

    In our study, we will use the PROMIS instruments Anxiety, Depression, Sleep disturbance and Satisfaction with social roles and activities. These are all short forms containing 8 questions or statements. Patients are asked to rate the questions from 1-5 into which extent they believe them to be true; 1 being not at all and 5 being very much. For each short form, a score will be calculated by adding the values of the response to each question. PROMIS provides a score conversion table where the score can be translated into a T-score. This rescales the patient's score into a standardized score with a mean of 50 and a standard deviation of 10. In order to provide these results, PROMIS uses a calibration sample containing data from over 21000 respondents. Differences in mean changes between baseline and end of study, as well as between the two study groups will be calculated using a paired T-test.

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Dec 2014 (estimated)
  2. Study startFeb 2015
  3. Primary completionJun 2017
  4. Study completionJun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02308332
Sponsor's protocol ID
ABR50959
Acronym
ESCAPE
Status last verified
Oct 2017
First submitted
24 Nov 2014
Last updated
27 Oct 2017
Results posted
No
Data monitoring committee
No

Publications

  • Oomen PGA, Hakkers CS, Arends JE, van der Berk GEL, Pas P, Hoepelman AIM, van Welzen BJ, du Plessis S. Underlying Neural Mechanisms of Cognitive Improvement in Fronto-striatal Response Inhibition in People Living with HIV Switching Off Efavirenz: A Randomized Controlled BOLD fMRI Trial. Infect Dis Ther. 2024 May;13(5):1067-1082. doi: 10.1007/s40121-024-00966-7. Epub 2024 Apr 20.

    PubMed 38642238

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Eviplera in people with Neurocognitive Decline and HIV Associated Neurocognitive Disorder, run by UMC Utrecht at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02308332, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2017.

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