- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT04887675
Neuroinflammation and Neurodegeneration in HIV-positive Subjects Switched and Initially Treated With INSTI
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.
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.
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Antecipado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Snezana Brkic
- Número de telefone: +38163570350
- E-mail: brkicsnezana@yahoo.com
Locais de estudo
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Novi Sad, Sérvia, 21000
- Recrutamento
- Faculty of Medicine, University of Novi Sad
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Contato:
- Snezana Brkic
- Número de telefone: +381603570350
- E-mail: brkicsnezana@yahoo.com
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-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Prevenção
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
---|---|
Comparador Ativo: Patients switched from PI/EFV based ART to INSTI based ART
60 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)
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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.
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Comparador Ativo: Patients initially treated with INSTI based regimens
60 patients initially started on INSTI based ART (raltegravir and dolutegravir), stable on treatment (undetectable viral load for at least 6 months).
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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.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Levels od inflammatory biomarkers in patients switched to INSTI based regimens
Prazo: 1 year
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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.
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1 year
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Performance performance on neurocognitive test in patients initially treated with INSTI based regimens
Prazo: 1 year
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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.
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1 year
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Incidence of metabolic syndrome in patients initially treated with INSTI based regimens
Prazo: 1 year
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Metabolic syndrome incidence will be described using relevant statistical parameters (frequency and incidence rate).
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1 year
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Snezana Brkic, University of Novi Sad
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Antecipado)
Conclusão do estudo (Antecipado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Processos Patológicos
- Distúrbios do Metabolismo da Glicose
- Doenças Metabólicas
- Doenças de pele
- Infecções por vírus de RNA
- Doenças Virais
- Infecções
- Infecções transmitidas pelo sangue
- Doenças Transmissíveis
- Doenças Sexualmente Transmissíveis, Virais
- Doenças Sexualmente Transmissíveis
- Infecções por Lentivírus
- Infecções por Retroviridae
- Síndromes de Deficiência Imunológica
- Doenças do sistema imunológico
- Resistência a insulina
- Hiperinsulinismo
- Distúrbios do metabolismo lipídico
- Infecções por HIV
- Doenças de Pele Metabólicas
- Síndrome metabólica
- Lipodistrofia
- Degeneração Nervosa
- Síndrome de lipodistrofia associada ao HIV
Outros números de identificação do estudo
- UNoviSad
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Informações sobre medicamentos e dispositivos, documentos de estudo
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