Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04887675 |
| Other study ID # |
UNoviSad |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2021 |
| Est. completion date |
October 1, 2022 |
Study information
| Verified date |
November 2021 |
| Source |
University of Novi Sad |
| Contact |
Snezana Brkic |
| Phone |
+38163570350 |
| Email |
brkicsnezana[@]yahoo.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Since the HIV changed its course to the chronic disease, high incidence of metabolic syndrome
both in HIV positive and negative subjects has become an issue. Given the successful
peripheral suppression of HIV after introduction of combined antiretroviral therapy (cART),
comorbidities associated with aging and cognitive functioning, play the main role in the
overall quality of life and adherence to the therapy. Continuous low-level neuroinflammation
results in continuous and diffuse neuronal death or dysfunction leading to a certain level of
neurodegeneration. Additionally, metabolic syndrome contributes to neurodegeneration causing
damage to the brain vasculature and provoking the ischemic incidents.
The aim of this study would be to explore the influence of switching to the INSTI based cART
using neuroimaging biomarkers of inflammation and neurodegeneration. The second aim would be
to monitor these neuroimaging biomarkers in patients receiving INSTI-based cART in a one-year
follow-up period. Additionally, we would compare the markers of metabolic syndrome and
cognitive functioning (executive functions) in HIV-positive patients after switching to
INSTI-based cART and in HIV-positive patients receiving INSTI-based cART from the start.
This study represents a single-center, prospective, interventional, two-armed single study.
Arm I will include 60 patients on PI/EFV based ART, stable on treatment, who are switched to
INSTI based regimen at the beginning of the study due to side effects or long-term toxicities
like hyperlipidemia, diarrhea, (PI), insomnia, headache (EFV), high Framingham score
(PI/EFV). Arm II will include 60 patients initially on INSTI-based ART, stable on treatment.
The same data sets will be collected for both groups of patients. The variables collected
will be related to metabolic syndrome (levels of LDL and HDL cholesterol, triglycerides,
fasting insulin, glucose, blood pressure, waist circumference, waist to hip and waist to
height ratio), performance on neurocognitive tests and MR spectroscopy neuroinflammation and
neurodegeneration markers at the beginning of the study, as well as in 12 months follow up.
Presence of steatosis and visceral fat thickness will be assessed using ultrasonography of
abdomen.
The primary imaging will be performed at the time of enrollment of patients, along with the
neurocognitive testing and blood sampling. The secondary imaging (follow up) will be
performed 12 months after the initial, also followed by neurocognitive assessment and blood
sampling.
Anthropometric measurements will be acquired at the time of blood sampling. Statistical
analysis will be performed after collecting the data. Our work could significantly contribute
to the better life quality in the aging of HIV positive subjects in the domain of cognitive
functioning, tightly associated with adherence and overall life quality.
Description:
Serbia is low income country with epidemiology of HIV infection resembling those in developed
countries, with average age of patients around 50 years and majority of them being the MSM
population. Another important issue is the high incidence of metabolic syndrome both in HIV
positive and negative subjects. With the successful peripheral suppression of HIV after
introduction of combination antiretroviral therapy (cART), HIV disease has changed its course
and now represents a chronic disease with majority of patients reaching senium. In these
patients, comorbidities associated with aging, especially in the means of cognitive
functioning, play the main role in the overall quality of life and adherence to the therapy.
Considering the fact that viral particles of HIV remain latent in microglial cells and
macrophages, virus only triggers the inflammatory response in the brain, which is afterwards
maintained in the form of low-level neuroinflammation by the microglia and macrophages,
resulting in continuous and diffuse neuronal death or dysfunction and leading to a certain
level of neurodegeneration. With aging of HIV-positive subject, this form of
neurodegeneration is combined with the physiological aging of the brain, most probably in the
synergistic manner. Recent studies showed that this peripheral inflammation alters the
blood-brain barrier and allows the penetration of HIV and particles, starting the "circulus
vitiosus" all over again. Additionally, metabolic syndrome contributes to neurodegeneration
causing damage to the brain vasculature and provoking the ischemic incidents.
The switch from the old fashion to the modern INSTI based cART and its influence on the
process of neurodegeneration, as well as the role of neuroprotection of INSTI are still not
well examined and documented. The aim of this study would be to explore the influence of
switching to the INSTI based cART on neuroimaging biomarkers of inflammation and
neurodegeneration obtained by MRS. The second aim would be to monitor these neuroimaging
biomarkers in patients receiving INSTI based cART from the start in a one-year follow up
period. Additionally, we would compare the markers of metabolic syndrome and cognitive
functioning (executive functions) in HIV-positive patients after switching to INSTI based
cART and in HIV-positive patients receiving INSTI based cART from the start.
This study represents a single-center, prospective, interventional, two-armed single study.
Arm I will include 60 patients on PI/EFV based ART, stable on treatment, who will be switched
to INSTI based regimen at the beginning of the study due to side effects or long-term
toxicities like hyperlipidemia, diarrhea, (PI), insomnia, headache (EFV), high Framingham
score (PI/EFV). Arm II will include 60 patients initially started on INSTI based ART, stable
on treatment. The same data set will be collected in both groups of patients. The variables
collected will be related to metabolic syndrome (levels of LDL and HDL cholesterol,
triglycerides, fasting insulin, glucose, blood pressure, waist circumference, waist to hip
and waist to height ratio), performance on neurocognitive tests and MRS neuroinflammation and
neurodegeneration markers at the beginning of the study, as well as the 12 months after the
beginning.
Besides the biochemical and anthropometric parameters of metabolic syndrome, presence of
steatosis and visceral fat thickness will be assessed using ultrasonography of abdomen.
The primary imaging will be performed at the time of enrollment of patients. At the same time
point, immediately before of after the imaging, patients will fulfill the neurocognitive
testing. Blood samples will be taken within one week prior to imaging. The secondary imaging
(follow up) will be performed 12 months after the initial, also followed by neurocognitive
assessment in the same time relationship. Blood samples will be taken within one week prior
to imaging.
Anthropometric measurements will be acquired at the time of blood sampling. Adequate
statistical analysis will be performed after collecting the data. Our work could
significantly contribute to the better life quality in the aging of HIV positive subjects in
the domain of cognitive functioning, tightly associated with adherence and overall life
quality.
