Clinical Trial Details
— Status: Terminated
Administrative data
NCT number |
NCT03163277 |
Other study ID # |
MARAND-X |
Secondary ID |
|
Status |
Terminated |
Phase |
Phase 4
|
First received |
|
Last updated |
|
Start date |
May 15, 2017 |
Est. completion date |
June 30, 2020 |
Study information
Verified date |
November 2020 |
Source |
University of Turin, Italy |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Neurocognitive disorders are still highly prevalent in the HAART era; despite a dramatic
reduction in dementia cases, 15-50% of patients may develop mild or asymptomatic
neurocognitive disorders (HIV-associated neurocognitive disorders, HAND).
Among other hypothesis neurotoxicity of antiretrovirals has been postulated but its impact is
unknown.
Our hypothesis is that using drugs with reduced in vitro neurotoxicity may improve cognition
in HIV-positive patients withHAND.
76 patients with HAND will be randomized to either continue their treatment or switch to
emtricitabine, darunavir/cobicistat, maraviroc. Patients will be re-tested 6 months later.
Description:
Scientific Rationale for Study / Scientific Study Objectives:
Neurocognitive disorders are still highly prevalent in the HAART era; despite a dramatic
reduction in dementia cases, 15-50% of patients may develop mild or asymptomatic
neurocognitive disorders (HIV-associated neurocognitive disorders, HAND). It should be
highlighted that patients presenting no abnormalities in everyday living activities
(asymptomatic neurocognitive disorders, ANI) are at higher risk of worse results in
performance-based tests, adherence-based measures and they show a significant risk of
progressing to more severe forms of impairment. Excluding significantly confounding
comorbidities, several factors have been associated with this neurocognitive decline
including a low nadir CD4+ T-lymphocyte count, a high HIV DNA, a lower compartmental viral
control, a lower concentration/penetration effectiveness score, a lower efficacy in
macrophage-derived cells and antiretroviral-generated neuronal toxicity. However several data
point out that vascular abnormalities, very common in HIV-positive patients, may deeply
influence neurocognitive disorders development and severity: of note, intima media thickness,
a well recognized proxy of systemic atherosclerosis, was associated with HAND.
In case of HAND diagnosis, the only recommended approach is to optimize treatment according
to plasma and cerebrospinal fluid (CSF) resistance tests; no strategy is currently suggested
in case of suppressed plasma and CSF HIV RNA or in case of low level CSF HIV RNA (without
evidence of genotypic resistance). It has been postulated that antiretrovirals may have
neurotoxic effects through different mechanisms and such effects might become evident once
the beneficial effect of HIV RNA suppression vanishes. Available data suggest that, in vitro,
the drugs associated with the least neurotoxic effect were emtricitabine, tenofovir,
darunavir and maraviroc. Furthermore, several pieces of evidence and a small randomized trial
suggest that maraviroc, in HAART-treated subjects may have beneficial effects in terms of
improved neurocognitive function, reduced CSF inflammatory biomarkers and improved MRI
markers of neuronal integrity.
No study has so far investigated the effect of using drugs with a low neurotoxic profile in
HAART-treated patients with HAND.
Primary objective of the study is the variation in neurocognitive tests (global deficit
score), 6 months after treatment switch while secondary objectives include the improvement in
other biomarkers of neuronal and vascular integrity.
Methods:
Study Design: Randomized, controlled, pilot study. HIV-positive patients that fulfill the
inclusion criteria and that sign the informed consent will be enrolled. Patients will be
randomized 1:1 (block randomization) to either continue their treatment or to switch to
once-daily emtricitabine (200 mg) plus darunavir/cobicistat (800/150 mg) plus maraviroc (300
mg). A lumbar puncture will be performed 6 months after treatment switch.
Number of Patients: 76 (38 per arm)