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HIV I InfectionNCT04887675

Neuroinflammation and Neurodegeneration in HIV-positive Subjects Switched and Initially Treated With INSTI

A study testing MRI in people with HIV I Infection and HIV Associated Lipodystrophy, run by University of Novi Sad at 1 site in Serbia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 45 years, men only
What is being tested?
MRI
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
1 siteSerbia
Study dates
1 May 2021to 1 Oct 2022
Phase
Interventional
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 18 to 45 years
  • Men only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Male (in order to eliminate the hormonal influences on the levels of brain metabolites),
  • older than 18 years,
  • HIV seropositivity confirmed on PCR testing,
  • undetectable viral load for over one year,
  • conventional magnetic resonance imaging (MRI) normal.
  • In group I, the additional criterion would be stable cART not containing INSTI for over one year.
  • In group II, the inclusion criteria will be the INSTI base regimen introduced at least one year prior to imaging.

Who cannot join

  • active infiltrative or infective/opportunistic neurological illness,
  • chronic neurological diseases (multiple sclerosis, vascular and non-vascular dementia, other neurodegenerative conditions),
  • active abuse of narcotic drugs,
  • hepatitis B or C coinfection,
  • deep white matter lesions (focal or diffuse, such as lacunar stroke, leukoaraiosis, infiltrative or infective foci, metastases etc.),
  • International HIV Dementia Scale (IHDS) score <10 (only neuro-asymptomatic subjects would be included in the study), and
  • contraindications for MRI examination

Trial locations and contacts

1 site in 1 country.

Serbia1 site, 1 recruiting
  • Faculty of Medicine, University of Novi Sad

    Novi Sad, 21000

    Snezana Brkic, +381603570350, brkicsnezana@yahoo.com

    Recruiting

Other trials in Serbia

About this study

Official title: A Single Centre, Prospective, Two-armed Magnetic Resonance Spectroscopy Study to Compare Imaging Biomarkers of Neuroinflammation and Neurodegeneration Between HIV-positive Subjects Switched and Initially Treated With INSTI

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.

Read more

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.

Read the detailed 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.

Being tested
MRI
Medical subject headings
HIV-Associated Lipodystrophy Syndrome, Metabolic Syndrome

What participants receive

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

  • MRIDiagnostic test

    Both groups with undergo neuroimaging on 3T magnetic resonance unit (Trio Tim, Siemens, Erlangen, Germany) in the Center for Diagnostic Imaging, Oncology Institute of Vojvodina, Serbia. Multivoxel MRS will be performed in the supratentorial cerebral parenchyma, covering white matter of frontal and parietal lobes, as well as cortical grey matter in frontal and parietal lobes and the whole cingulate gyrus.

Study groups in NCT04887675
Study groupRoleWhat they receive
Patients switched from PI/EFV based ART to INSTI based ARTActive comparator60 patients on PI/EFV based ART, stable on treatment (undetectable viral load for at least 6 months). At the beginning of the study they are switched to INSTI based regimen. The reasons for the switch will be side effects or long-term toxicities like hyperlipidemia, diarrhea, (PI), insomnia, headache (EFV), high Framingham score (PI/EFV)
Receives: Diagnostic Test: MRI
Patients initially treated with INSTI based regimensActive comparator60 patients initially started on INSTI based ART (raltegravir and dolutegravir), stable on treatment (undetectable viral load for at least 6 months).
Receives: Diagnostic Test: MRI

What is being measured

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

  1. Levels od inflammatory biomarkers in patients switched to INSTI based regimens

    We will assess neuroimaging biomarkers obtained on magnetic resonance spectroscopy. These markers are: N-acetyl aspartate (NAA, marker of neuronal density and function), choline (Cho, marker of membrane metabolism and degradation), myoinositol (mI, marker of glial proliferation) and creatine (Cr, reference marker and marker of energy depot). These markers will be derived as ratios: NAA/Cr, Cho/Cr and mI/Cr.

    Measured: 1 year

Secondary outcomes (2)
  1. Performance performance on neurocognitive test in patients initially treated with INSTI based regimens

    Neurocognitive testing will be performed using validated battery of neurocognitive tests (Montreal Cognitive Assessment, MoCA), consisted of relevant tests for memory deficits, executive functions, attention and concentration.

    Measured: 1 year

  2. Incidence of metabolic syndrome in patients initially treated with INSTI based regimens

    Metabolic syndrome incidence will be described using relevant statistical parameters (frequency and incidence rate).

    Measured: 1 year

Timeline

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

  1. First posted14 May 2021
  2. Study start1 May 2021
  3. Primary completion1 Jun 2022 (estimated)
  4. Study completion1 Oct 2022 (estimated)

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 N/A
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Care provider, Investigator
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04887675
Sponsor's protocol ID
UNoviSad
Status last verified
Nov 2021
First submitted
30 Apr 2021
Last updated
1 Dec 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing MRI in people with HIV I Infection and HIV Associated Lipodystrophy, run by University of Novi Sad at 1 site in Serbia.

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 7 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 1 Dec 2021. 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 Serbia. 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.

Are results available for this study?

Results are not available in the source record.

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

Contact Snezana Brkic (+38163570350, brkicsnezana@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Levels od inflammatory biomarkers in patients switched to INSTI based regimens (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 1 Dec 2021.

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