E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients infected with human immunodeficiency virus who have never received antiretroviral treatment. |
Pacientes infectados con virus de inmunodeficiencia humana que nunca han recibido tratamiento antirretroviral. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Changes in the levels of N-acetyl-aspartate (NAA) in the basal brain ganglia |
Variación de los niveles de N-Acetil-Aspartato (NAA) en los ganglios basales cerebrales |
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E.2.2 | Secondary objectives of the trial |
- Change in neurocognitive functioning
- Changes in the levels of NAA in the frontal lobe
- Changes in the levels of choline, myoinositol and glutamate in the basal ganglia and frontal lobe
- Change in the volume of brain structures
- Changes in the white matter abnormalities
- Virologic failure
- Therapeutic failure
- Changes in the levels of CD4
- Adherence to HAART
- Adverse effects |
- Variación del funcionamiento neurocognitivo
- Variación de los niveles de NAA en el lóbulo frontal
- Variación de los niveles de Colina, mioinositol y glutamato en los ganglios basales y el lóbulo frontal
- Variación del volumen de las estructuras cerebrales
- Variación de las anomalías de la sustancia blanca
- Fallo virológico
- Fallo terapeútico
- Variación de los niveles de CD4
- Adherencia al TARGA
- Efectos adversos |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- HIV-positive by ELISA and confirmed by WB
- Age> 18 years
- Never have received antiretroviral treatment for HIV
- CV baseline of HIV> 100,000 copies / mL
- No evidence of genotypic resistance against antiretroviral
- Study HLA B5701 negative
- Having a VL <100,000 copies / mL
- Able to understand and give written informed consent.
- Meet the criteria to initiate the AR treatment according to Gesida 2012 Guideline.
-Women of childbearing potential should have a pregnancy test negative in blood or urine during the 7 days prior to initiation of therapy and postmenopausal women should have amenorrhea for at least 12 months to consider that they are of childbearing age.
- Non pregnant or lactating without heterosexual activity during the entire study or heterosexual activity and willing to use two methosds of contraception. The two methods of contraception can be 2 barrier methods or a barrier method and a method to prevent pregnancy hormone, used during the entire study and for 12 weeks after completion. |
-VIH positivo mediante ELISA y confirmado mediante WB
- Edad > 18 años
- No haber recibido nunca tratamiento antiretroviral frente al VIH
- CV basal de VIH > 100.000 copias/mL
- Ausencia de evidencia de resistencias genotípicas frente a antiretrovirales
- Estudio HLA B5701 negativo
- Tener una CV < 100.000 copias/mL
- Capaz de entender y dar su consentimiento informado por escrito.
- Cumplir criterios para el inicio del tratamiento antirretroviral de acuerdo con las recomendaciones recogidas en las guías de GESIDA 2012.
- Las mujeres en edad fértil deberán tener una prueba de embarazo en sangre o en orina negativa durante los 7 días anteriores al Inicio del tratamiento y las mujeres posmenopáusicas deben presentar amenorrea desde hace al menos 12 meses para considerar que no están en edad fértil.
- Puede incluirse a mujeres no embarazadas ni lactantes sin actividad heterosexual durante la totalidad del estudio O con actividad heterosexual y dispuestas a utilizar 2 métodos anticonceptivos. Los 2 métodos anticonceptivos pueden ser 2 métodos de barrera 0 un método de barrera y un método hormonal para prevenir el embarazo, utilizados durante la totalidad del estudio y hasta 12 semanas tras la finalización del mismo.
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating women and women of childbearing age who are not committed to use adequate contraception method.
2. Previous history of serious confounding neurological comorbidities defined as:
- Dependence on drugs or alcohol
- CNS opportunistic infections
- Major depression or psychosis
- Previous diagnosis of dementia
- Mental retardation
- CNS neurological disease
- Co-infection with hepatitis C virus
3. Claustrophobia
4. Existence of magnetizable body devices
5. Inability to perform and complete a full neurologic assessment
6. Renal insufficiency (creatinine clearance <60 mL / min)
7. Diabetes mellitus or cardiovascular risk> 10% calculated by Framingham
8. The following analytical criteria:
- Neutropenia <750 cells / ?L
- Hemoglobin <8.0 g / dL
- Platelets <50,000 cells / ?L
- Levels of GOT, GPT and GGT greater than 5 times the baseline levels |
1. Mujeres embarazadas o lactantes, así como mujeres en edad fértil que no se comprometan a utilizar un método anticonceptivo adecuado2. Historia previa de comorbilidades neurológicas de confusión graves definidas como:
- Dependencia de drogas o alcohol
- Infecciones oportunistas del SNC
- Depresión mayor o psicosis
- Diagnóstico previo de demencia
- Retraso mental
- Enfermedad neurológica del SNC
- Coinfección por el virus de la hepatitis C
3. Claustrofobia
4. Existencia de dispositivos corporales magnetizables
5. Inhabilidad para realizar y completar una evaluación neurológica completa
6. Presencia de insuficiencia renal (Aclaramiento de creatinina <60 mL/min)
7. Diabetes mellitus o un riesgo cardiovascular > 10% calculado por Framingham
8. Los siguientes criterios analíticos:
- Neutropenia < 750 células/?L
- Hemoglobina < 8,0 g/dL
- Plaquetas < 50.000 células/?L
- Niveles de GOT, GPT o GGT superiores a 5 veces los niveles de referencia |
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E.5 End points |
E.5.1 | Primary end point(s) |
Variation of NAA levels in the cerebral basal ganglia, measured by NMR spectroscopy between two different HAART regimens with different penetration in the CNS |
Variación de los niveles de NAA en los ganglios basales cerebrales, medidos mediante RMN con espectroscopia entre dos regímenes de TARGA con distinta penetración en el SNC |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 24 |
Desde la visita basal hasta la semana 24 |
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E.5.2 | Secondary end point(s) |
1-Variation of the "Global Defict Score" (GDS)
2-Variation of NAA levels in the structures of the frontal cortex as measured by NMR spectroscopy
3-Glutamate and choline levels in the basal ganglia structures and frontal cortex as measured by NMR spectroscopy
4-Evolution of brain volumes measured by MRI volumetry
5-White matter abnormalities on MRI measured by MRI, by anisotropy
6-HIV-CV> 50 copies / mL. Development of resistance mutations to any of the antiretrovirals used
7-Modification of HAART for another with different CNS penetration (exchange of CPE Score> ± 1); presence of virological failure, loss or removal of the monitoring from the study for any reason
8-Variation in the absolute levels of CD4 +
9-Levels of adherence to HAART, as measured by adherence questionnaire GEMMA
10-Number of general and specific adverse effects of CNS related and unrelated to HAART, and cumulative incidence of them |
1-Variación del "Global Defict Score" (GDS)
2-Variación de los niveles de NAA en las estructuras de la corteza frontal, medidos mediante RMN con espectroscopia
3-Niveles de colina y glutamato en las estructuras de los ganglios basales y la corteza frontal, medidos mediante RMN con espectroscopia
4-Evolución de los volúmenes cerebrales medidos mediante volumetría por RMN
5-Anomalías en la sustancia blanca medidas por RMN, mediante anisotropía
6-CV de VIH > 50 copias/mL. Desarrollo de mutaciones de resistencia a alguno de los antiretrovirales utilizados
7-Modificación del TARGA por otro con distinta penetración en el SNC (cambio del CPE Score > ± 1); presencia de fallo virológico; pérdida de seguimiento o retirada del estudio por cualquier razón
8-Variación de los niveles absolutos de linfocitos CD4+
9-Niveles de adherencia al TARGA, medidos por el cuestionario de adherencia GEMMA
10-Número de efectos adversos generales y específicos del SNC relacionados y no relacionados con el TARGA; incidencia acumulada de los mismos |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-From baseline to week 24
2-From baseline to week 24
3-From baseline to week 24
4-From baseline to week 24
5-From baseline to week 24
6-From baseline to week 24
7-From baseline to week 24
8-From baseline to week 24
9-Baseline and weeks 4, 12 and 24
10-Baseline and weeks 4, 12 and 24 |
1-Desde la visita basal hasta el la semana 24
2-Desde la visita basal hasta el la semana 24
3-Desde la visita basal hasta el la semana 24
4-Desde la visita basal hasta el la semana 24
5-Desde la visita basal hasta el la semana 24
6-Desde la visita basal hasta el la semana 24
7-Desde la visita basal hasta el la semana 24
8-Desde la visita basal hasta el la semana 24
9-Visitas basal y semanas 4, 12 y 24
10-Visitas basal y semanas 4, 12 y 24 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LPLV |
Ultima visita del último paciente |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |