E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy voulnteers carrying a mutation in at least one of the following genes: PSEN1, PSEN2 or APP. |
Voluntarios sanos portadores de mutación en al menos uno de los siguientes genes: PSEN1, PSEN2 o APP. Voluntarios sanos no portadores de mutación. |
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E.1.1.1 | Medical condition in easily understood language |
Healthy volunteers with familial Alzheimer disease. |
Voluntarios sanos con enermedad de Alzheimer familiar genético |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10001897 |
E.1.2 | Term | Alzheimer's disease (incl subtypes) |
E.1.2 | System Organ Class | 100000004852 |
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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 |
1. To assess safety of a single dose of FBB followed by PET scan in individuals at risk of genetic Alzheimer?s disease. 2. To determine the number of Familiar Alzheimer´s disease (FAD) mutation carriers with positive FBB-PET at visual assessment. |
1.-Evaluar el perfil de seguridad de FBB-PET en individuos con riesgo genético de enfermedad de Alzheimer.
2.-Determinar el número de portadores de mutaciones asociadas a enfermedad de Alzheimer familiar (FAD) que presentan captación positiva en el análisis visual y semicuantitativo de FBB-PET |
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E.2.2 | Secondary objectives of the trial |
1. To determine the number of FAD mutation carriers with abnormally high standardized uptake value ratios (SUVRs) of FBB-PET scan. 2. To compare global SUVR scores of FBB-PET scan between mutation carriers and non-carriers. 3. To study the earliest age of FAD mutations carriers with positive FBB-PET scan at visual assessment. 4.-To explore the cortical pattern of amyloid deposition in FAD mutations carriers |
1.- Determinar el número de portadores de mutaciones asociadas a Alzheimer familiar (FAD) que presentan valores estandarizados de captación anormalmente altos en el FBB-PET.
2.- Comparar los valores estandarizados de captación globales del FBB-PET entre los portadores y no portadores de mutación.
3.- Describir la edad más temprana en la que los portadores de mutación FAD presentan captación positiva en el FBB-PET en el análisis visual.
4.- Explorar el patrón cortical de deposición amiloide en individuos portadores de mutaciones FAD. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult children (> 18 yo) of genetic Alzheimer?s disease patients with a known mutation in PSEN1, APP o PSEN2 genes and who are either cognitively normal (CDR=0) or have mild symptoms of cognitive decline (CDR 0.5 or 1) 2. According to the principal investigator, participants must be committed to participate and complete all study procedures. 3. Has signed the Informed Consent Form voluntarily to participate in the study |
1. Hijos adultos (> 18 años) de pacientes con enfermedad de Alzheimer genético con una mutación conocida en los genes PSEN1, PSEN2 o APP, cognitivamente normales (CDR=0) o con signos leves de deterioro cognitivo (CDR 0.5 o 1). 2. A criterio del investigador principal, los participantes deben comprometerse a cumplir todos los procedimientos del estudio. 3. Firma voluntaria de consentimiento informado. |
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E.4 | Principal exclusion criteria |
1. Subjects that are not able to complete the study. 2. Any major disease or history of a major disease, especially hepatobilliar disease (AST /ALT ? 5 x ULN) or advanced renal insufficiency (creatinine ? 2 x ULN) 3. Current or previous history of alcohol abuse or epilepsy 4. Allergic to Florbetaben or any of its constituents 5. Multiple drug allergies and/or previous history of contrast allergy. 6. Pregnancy or breast feeding or planned pregnancy during the study period 7. Any disease or history of disease which, in the opinion of the investigator, can cause disturbance of brain function (e.g. vitamin B12 or folic acid deficiency, disturbed thyroid function) 8. Evidence for any other neurological or psychiatric disease |
1. Sujetos que no puedan completar el estudio 2. Cualquier enfermedad grave previa o actual especialmente, enfermedad hepatobiliar (GOT/GPT ? 5 LSN) o insuficiencia renal avanzada (creatinina ? 2 LSN) 3. Historia de consumo abusivo de alcohol previo o actual o epilepsia 4. Alergia a florbetaben o alguno de sus componentes. 5. Múltiples alergias a fármacos o antecedentes previos de alergia a contraste 6. Mujeres embarazadas o en periodo de lactancia o que hayan planeado quedarse embarazadas durante el periodo del estudio. 7. Cualquier enfermedad o antecedente previo que en opinión del investigador pueda alterar la función cerebral (deficiencia de vitamina B-12 o ácido fólico, alteración de la función tiroidea) 8. Evidencia de cualquier otra enfermedad neurológica o psiquiátrica. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence of Adverse events of a single dose of FBB followed by PET scan in individuals at risk of genetic Alzheimer?s disease. 2. Proportion of FAD mutation carriers that present positive uptake after FBB-PET through visual examination |
1.- Incidencia de acontecimientos adversos tras la administración de una única dosis de FBB durante el PET en individuos con riesgo de enfermedad de Alzheimer genético. 2.- Proporción de portadores de mutación FAD que presentan captación positiva de FBB en el PET medida por exámen visual. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline, when FBB-PET is performed. |
En el momento basal, cuando se realiza el FBB-PET. |
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E.5.2 | Secondary end point(s) |
1. Proportion of FAD mutation carriers presenting standardized uptake value ratios (SUVRs) of FBB-PET higher than 1,4. 2. Areas of significant difference (p<0,05) in regional SUVR between FAD mutation carriers and non-carriers. 3. Earliest age of positive FBB-PET in FAD mutation carriers. 4. Individual cortical areas with positive amyloid deposition at visual or semi-quantitative assessment |
1.- Proporción de portadores de mutación FAD que presentan valores estandarizados de captación (SUV) en el FBB-PET superiores a 1.4.
2.- Áreas con un valor estandarizado de captación regional significativamente diferente (p<0,05) en los portadores y no portadores de mutación.
3.- Edad más temprana en la que los portadores de mutación FAD presentan captación positiva en el FBB-PET.
4.- Áreas individuales corticales con deposición positiva de amiloide en el examen visual o semi-cauntitativo. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at baseline |
en el momento basal |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
controlado con no portadores |
controlled with non-carriers |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
no portadores |
non-carriers |
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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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The end of the trial will be defined by the last visit of the last patient. |
El final del estudio se corresponderá con la última 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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |