- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01978743
Advanced Neuroimaging Evaluation of CNS Changes Associated With Efavirenz Therapy Switch to an Raltegravir-based Regimen
Advanced Neuroimaging Evaluation of the Central Nervous System Biological Changes Associated With Efavirenz Therapy Switch to an Raltegravir-based Regimen
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
In a cohort of HIV-infected patients who are clinically stable on the commonly use regimen of EFV/emtricitabine (FTC)/truvada (TDF) or Atripla, investigators propose to replace the EFV component with an integrase inhibitor, Raltegravir (RAL), given as the RAL and FTC/TDF to evaluate the EFV-related neural alterations. This is a multidisciplinary study which will be lead by Dr. Nina Lin, in collaboration with the research teams of Dr. Alexander Lin, Director of the Center for Clinical Spectroscopy, and Dr. Emily Stern, Director of the Functional Neuroimaging Laboratory, both members of the Brigham and Women's Department of Radiology at Harvard Medical School, as well as Dr. Jane Epstein, a researcher in Dr. Stern's research group. Dr. Epstein is a staff psychiatrist at Brigham and Women's hospital with extensive experience and expertise in research on abnormalities of affective and motivational processing in the context of neuropsychiatric disorders. Investigators will utilize the established clinical research platform in the Infectious Disease outpatient clinical practice at the Brigham and Women's Hospital, where there is currently have many ongoing HIV-related studies and a large panel of HIV-infected patients motivated to be involved in clinically relevant research. Investigators propose to use advanced neuroimaging to measure biologically changes in the brain associated with long-term EFV use with the following specific aims:
- Determine changes in neurometabolites measured by MRS in the brain associated with long-term EFV use
- Assess for alterations in neural activity correlated with affective symptoms associated with EFV vs RAL use using fMRI, and their associations with changes in neurometabolites assessed by MRS, and with changes in cognition assessed by Trail Making and Digit Substitution Tests.
- Determine changes in emotion, cognition and sleep quality after switching from EFV to RAL, and how they correlate with subject treatment preference.
This clinical study will extend our current understanding of EFV neurotoxicity by further defining the nature of these biological changes. Further elucidation of the neurobiological underpinnings of EFV-induced CNS toxicity will have clinical relevance in improving the quality of life and drug adherence of HIV-infected patients on ART, especially among older patients or those with baseline neuropsychiatric disorders, whom at baseline are more vulnerable to neurocognitive decline from long-term HIV infection.
Tipo de estudio
Inscripción (Actual)
Fase
- No aplica
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Massachusetts
-
Boston, Massachusetts, Estados Unidos, 02115
- Brigham and Women's Hospital
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Chronic HIV-infected individuals on suppressive regimen with EFV/FTC/TDF, for at least 6 months
- Undetectable HIV-1 RNA virus load for at least 6 months
- No co-infections with active hepatitis B and C
- Presence of at least moderate symptoms on 2 out of 3 subcores on the DASS
- No known active HIV-related and non-HIV related CNS infections
- Estimated glomerular filtration rate (EGFR) >60 ml/min
- Consent to switching to EVG/COBI/FTC/TDF
- Ages 18 - 65
Exclusion Criteria:
- History of CNS opportunistic infections or active CNS infections
- History of severe psychiatric disorder (excluding depression and anxiety)
- History of chronic neurological disorders, such as epilepsy or multiple sclerosis
- History of or current significant substance abuse or dependence and/or heavy alcohol use (>12 oz/wk)
- Any women who may be pregnant (positive urine pregnancy test or unprotected sex in 2 weeks prior to scan) or known to be pregnant
- Contraindications to undergoing fMRI, including metallic implants, claustrophobia, and medical conditions or medications that significantly affect cerebral blood flow or function.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: Raltegravir
Switch from Atripla (EFV/FTC/TDF) to raltegravir (RAL) + Truvada (FTC/TDF).
Raltegravir will be administered 400mg twice-a-day with Truvada for 8 weeks.
|
Switch from Atripla to Raltegravir 400mg BID + Truvada (FTC/TDF) for total of 8 weeks
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS)
Periodo de tiempo: week 0 and week 8
|
Assess the levels of neuro-metabolites measured by MRS at week 0 before switching to the efavirenz-based therapy.
Two areas of the brain: 1) posterior cingulate gyrus and 2) anterior cingulate will be assessed for the levels of brain creatine (Cr), gamma-aminobutyric acid (GABA) and glutathione (GLU).
|
week 0 and week 8
|
Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI)
Periodo de tiempo: week 0 and week 8
|
Assess changes in neural activation correlated with affective disturbances associated with EFV vs. RAL using fMRI employing a paradigm that probes affective symptomatologies typical with EFV use; anxiety/dysphoria and affective dysregulation, and their association with changes in cognitive function.
Four brain regions of interests (ROIs) are specified to show the differential frontal-limbic activation patterns in the task-evoked neural responses to the 3 linear contrasts of Pre-/Post-/ Pre-vs.
Post-switch: [Negative Word vs. Neutral Word] x [No-Go Trial Block vs. Go Trial Block]: anterior Frontal Pole (aFP), posterior Cingulate Gyrus (pCG), dorsal anterior Cingulate Gyrus (daCG), Left Hippocampus (LHC).
A linear mixed-effects model is utilized to examine the effect sizes of the key Regimen/Condition contrasts, with the Subject factor as the random-effect, and Age incorporated as a co-variate of no interest.
A z-score is the Mean with a SD=1 and Measure of Dispersion equal to 1.
|
week 0 and week 8
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Other Neurometabolite Changes Measured by MRS
Periodo de tiempo: week 0 and week 8
|
Use MRS to evaluate a fuller panel of known neurometabolites (in addition to the primary endpoints) to evaluate for prominent and significant changes associated with EFV use.
|
week 0 and week 8
|
Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI
Periodo de tiempo: week 0 and week 8
|
Assess for changes in cognitive and affective function prior to and after switching off EFV-based regimen. Indexes used to access neurocognitive changes included:
|
week 0 and week 8
|
Fasting Lipid Profile
Periodo de tiempo: week 0 and week 8
|
Measure the change in fasting lipid panel prior to and after switching off EFV-based regimen.
|
week 0 and week 8
|
Sleep Quality
Periodo de tiempo: week 0 and week 8
|
Assess for changes in sleep pattern and quality prior to and after switching off EFV-based regimen through a self-administered Pittsburg Sleep Quality Index (PSQI).
Measure consists of 19 items with each weighted on 0-3 scale and the sum produces a total score, which ranges from 0-21.
The lower the score the healthier the sleep quality.
|
week 0 and week 8
|
ART Regimen Preference
Periodo de tiempo: week 0 and week 8
|
Evaluate patient preference in ART regimen (Atripla, EFV/FTC/TDF versus RAL + FTC/TDF) through self-administered questionnaires.
|
week 0 and week 8
|
Markers of Immune Activation
Periodo de tiempo: week 0 and week 8
|
Change in markers of immune activation and inflammation associated with change to RAL (ie, sCD14, IL-6, hsCRP, D-dimer, CRP, LPS, sCD163, EndoCab)
|
week 0 and week 8
|
Change in Level of EFV and Metabolites
Periodo de tiempo: week 0 and week 8
|
Correlate change in level of EFV and metabolites with neurocognitive and neuroimaging changes
|
week 0 and week 8
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Nina Lin, MD, Massachusetts General Hospital
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Desordenes mentales
- Trastornos inducidos químicamente
- Enfermedades del Sistema Nervioso
- Envenenamiento
- Síndromes de neurotoxicidad
- Trastornos neurocognitivos
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Antivirales
- Inhibidores de enzimas
- Agentes Anti-VIH
- Agentes antirretrovirales
- Inhibidores de la integrasa del VIH
- Inhibidores de la integrasa
- Raltegravir Potasio
Otros números de identificación del estudio
- NeuroHIV002
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre VIH
-
Icahn School of Medicine at Mount SinaiIRRASReclutamientoHemorragia Intraventricular (HIV)Estados Unidos
-
Yale UniversityTerminadoPrecocidad | Recién nacidos de muy bajo peso al nacer | Hemorragia Intraventricular (HIV) | Sangrado en el cerebroEstados Unidos
-
China Medical University HospitalDesconocidoDisplasia broncopulmonar | Bebés extremadamente prematuros | TLP grave que las terapias convencionales han fallado | Sin anomalías congénitas graves | no Hiv Severa Ni FPV QuísticaTaiwán
Ensayos clínicos sobre Raltegravir
-
National Institute of Allergy and Infectious Diseases...Eunice Kennedy Shriver National Institute of Child Health and Human Development...TerminadoInfecciones por VIHEstados Unidos, Puerto Rico, Sudáfrica, Argentina, Brasil, Botsuana
-
ViiV HealthcareTerminadoInfección, Virus De La Inmunodeficiencia HumanaEstados Unidos
-
Merck Sharp & Dohme LLCTerminado
-
ViiV HealthcareGlaxoSmithKline; ShionogiTerminadoInfecciones por VIH | Infección, Virus De La Inmunodeficiencia HumanaEstados Unidos, Francia, Países Bajos, España, Taiwán, Australia, Bélgica, Federación Rusa, Canadá, Reino Unido, México, Italia, Sudáfrica, Rumania, Argentina, Hungría, Polonia, Chile, Grecia, Brasil
-
ViiV HealthcareGlaxoSmithKline; ShionogiTerminadoInfección por el Virus de la Inmunodeficiencia Humana IAlemania, España, Francia, Australia, Estados Unidos, Canadá, Reino Unido, Italia, Federación Rusa
-
IrsiCaixaTerminado
-
ANRS, Emerging Infectious DiseasesTerminadoInfección por VIH-1 | EL EMBARAZOFrancia
-
National Institute of Allergy and Infectious Diseases...TerminadoInfecciones por VIH | TuberculosisSudáfrica
-
Arbeitsgemeinschaft medikamentoese TumortherapieMerck Sharp & Dohme LLCTerminado