ES2556535T3 - Uso de ensayo genómico y compuestos cetogénicos para tratamiento de una función cognitiva reducida - Google Patents

Uso de ensayo genómico y compuestos cetogénicos para tratamiento de una función cognitiva reducida Download PDF

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ES2556535T3
ES2556535T3 ES13167176.0T ES13167176T ES2556535T3 ES 2556535 T3 ES2556535 T3 ES 2556535T3 ES 13167176 T ES13167176 T ES 13167176T ES 2556535 T3 ES2556535 T3 ES 2556535T3
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Samuel T. Henderson
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Cerecin Inc
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Accera Inc
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Abstract

Un método para seleccionar un paciente para tratamiento de función cognitiva reducida relacionada con la enfermedad causada por reducción del metabolismo neuronal asociada con la enfermedad de Alzheimer (EA), método que comprende: a. seleccionar un paciente que tiene reducción de la función cognitiva relacionada con la enfermedad causada por reducción del metabolismo neuronal asociada a la enfermedad de Alzheimer (EA); b. determinar en el paciente la presencia de homocigosis para adenina de rs2229765 de Precursor de Receptor de tipo Insulínico (IGF1 R) en una porción relevante mostrada por la SEC ID Nº: 6; y c. seleccionar un paciente que tiene el genotipo específico en (b) para tratamiento, en el que el tratamiento comprende la administración al paciente de al menos un triglicérido de cadena media (MCT) en una cantidad eficaz para el tratamiento o la prevención de la reducción de la función cognitiva relacionada con la enfermedad por metabolismo neuronal reducido asociado a la enfermedad de Alzheimer.

Description

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Sujetos
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APOE rs448647. No se observaron efectos significativos con este alelo.
rs405509 de APOE. Los sujetos que eran heterocigotos en el sitio rs405509 demostraban un aumento de 3,68 puntos en la puntuación de ADAS-Cog cuando se comparan con el placebo (p = 0,0085). rs769446 de APOE. No se observaron efectos significativos con este alelo.
Tabla 2 Tratamiento por Genotipo
Cambio en ADAS-Cog a Partir de la Medida Inicial el Día 90
Genotipo de Tratamiento* con Anova de 2 vías
Snp
Genotipo N para AC-1202 N para Placebo P-valor
rs449647 de APOE
a 39 38 0,147
Het
17 11 0,14
t
3 3 0,4
rs405509 de APOE
g 11 7 0,48
Het
26 27 0,0085
t
23 18 0,629
rs769446 de APOE
Het 5 6 0,405
t
55 46 0,0951
rs1803274 de BUCHE
a 2 Na
g
40 39 0,541
Het
25 15 0,0133
rs2251101 de IDE
C 9 7 0,079
Het
22 25 0,0068
t
36 24 0,266
rs2229765 de IGF1R
A 5 13 0,00719
G
27 18 0,156
het
34 25 0,826
rs28401726 de IGF1R
C 52 48 0,0578
het
14 5 0,901
G
2 Na
rs16944 de IL1B
C 29 27 0,0145
het
28 17 0,845
T
6 9 0,479
rs1143627 de IL1B
C 6 9 0,479
Genotipo de Tratamiento* con Anova de 2 vías
Snp
Genotipo N para AC-1202 N para Placebo Valor de P
het
28 17 0,845
T
29 27 0,0145
rs11669576 de LDLR8
G 59 51 0,025
het
8 5 0,458
rs688 de LDLR13
C 24 22 0,987
23
het
33 20 0,061
T
7 13 0,061
rs2738447 de LDLR13
A 13 11 0,77
C
18 21 0,037
het
32 22 0,176
rs7259278 de LDLR13
G 44 44 0,0236
het
17 8 0,403
T
2 2 0,974
rs1799898 de LDLR 13
C 40 35 0,045
het
18 15 0,126
T
1 1 0,819
rs662 de PON1
A 28 26 0,12
G
6 7 0,239
het
32 23 0,73
rs2251101 de IDE
c/c 9 7 0,079
otro
58 49 0,0059
fuente del programa de AI: phg Tab 3
imagen21 imagen22 imagen23
ADCS-CGIC y MMSE
Cuando se comparan AC-1202 y Placebo en la población de ITT usando LOCF, AC-1202 no conducía a una diferencia significativa en la distribución de las puntuaciones de ADCS-CGIC en cualquier estudio.
Tabla 2 Tratamiento por Genotipo: Puntuación de ADCS-CGIC el Día 90
Valor de P del Genotipo de Tratamiento* con Anova de 2 vías
Snp
genotipo N para Ketasyn N para Placebo
Apoe4
0 1 29 39 26 31 0,218 0,769
rs449647 de APOE
a het t 39 17 3 38 11 33 0,201 0,604 0,796
rs405509 de APOE
g het t 11 26 23 7 27 18 0,6868 0,5660 0,7090
rs769446 de APOE
het t 5 55 6 46 0,441 0,274
rs1803274 de BUCHE
a g het 2 40 25 39 15 Na 0,356 0,574
rs2251101 de IDE
c het t 9 22 36 7 25 24 0,789 0,569 0,259
rs2229765 de IGF1R
a g het 5 27 34 13 18 25 0,350 0,871 0,585
rs28401726 de IGF1R
c het g 52 14 48 5 2 0,299 0,292 Na
24
rs16944 de IL1B
c het t 29 28 6 27 17 9 0,839 0,492 0,437
rs1143627 de IL1B
c het t 6 28 29 9 17 27 0,437 0,492 0,839
rs11669576 de LDLR8
g het 59 8 51 5 0,538 0,935
rs688 de LDLR13
c het t 24 33 7 22 20 13 0,436 0,662 0,295
rs2738447 de LDLR13
a c het 13 18 32 11 21 22 0,635 0,993 0,147
rs7259278 de LDLR13
g het t 44 17 2 44 8 2 0,288 0,552 1
rs1799898 de LDLR 13
c het t 40 18 1 35 15 1 0,175 0,986 0,321
rs662 de PON1
a g het 28 6 32 26 7 23 0,408 0,975 0,722
rs2251101 de IDE
c/c otro 9 58 7 49 0,494 0,790
fuente del programa de AI: phg Tab 5
imagen24
Se encontraron efectos significativos del tratamiento en el cambio a partir de la Medida Inicial en MMSE en Vehículos de rs405509 de APOE y rs662 de PON1.
Tabla 3 Tratamiento por Genotipo: Cambio en MMSE a partir de la Medida Inicial el Día 90
Valor de P del Genotipo de Tratamiento* con Anova de 2 vías
Snp
genotipo N para Ketasyn N para Placebo
Apoe4
0 1 29 39 26 31 0,369 0,704
rs449647 de APOE
A het T 39 17 3 38 11 33 0,595 0,424 0,277
rs405509 de APOE
G het T 11 26 23 7 27 18 0,929 0,067 0,037
rs769446 de APOE
het T 5 55 6 46 0,504 0,834
rs1803274 de BUCHE
A G het 2 40 25 39 15 Na 0,892 0,413
rs2251101 de IDE
C het T 9 22 36 7 25 24 0,908 0,206 0,111
rs2229765 de IGF1R
A G het 5 27 34 13 18 25 0,125 0,929 0,844
25
rs28401726 de IGF1R
C het G 52 14 48 5 2 Na 0,392 0,254
rs16944 de IL1B
C het T 29 28 6 27 17 9 0,846 0,943 0,879
rs1143627 de IL1B
C het T 6 28 29 9 17 27 0,879 0,943 0,846
rs11669576 de LDLR8
G het 59 8 51 5 0,756 0,762
rs688 de LDLR13
C het T 24 33 7 22 20 13 0,240 0,365 0,468
rs2738447 de LDLR13
A C het 13 18 32 11 21 22 0,709 0,265 0,513
rs7259278 de LDLR13
G het T 44 17 2 44 8 2 1 0,903 0,859
rs1799898 de LDLR 13
C het T 40 18 1 35 15 1 0,322 0,145 0,799
rs662 de PON1
A G het 28 6 32 26 7 23 0,085 0,031 0,287
rs2251101 de IDE
c/c otro 9 58 7 49 0,682 0,909
fuente del programa de AI: phg Tab 4
imagen25
Sucesos Adversos que se Producen Antes y Después de un Cambio en el Protocolo de Dosificación
Durante los primeros varios meses del estudio, parecía que se retiraría el estudio un número relativamente elevado
5 de sujetos debido a sucesos adversos gastrointestinales, en particular, por diarrea y flatulencia. Después de una evaluación de las razones dadas para la interrupción, se recomendó que la medicación del estudio o el placebo se deberían mezclar con una bebida con alto contenido de proteína (Ensure™) para aumentar la tolerabilidad del producto en investigación. Se informó de esta decisión a los sitios clínicos y posteriormente se les proporcionó un amplio suministro de Ensure para distribución a los sujetos del estudio. Aunque no se recogieron datos específicos
10 con respecto a que sujetos se adherían a las instrucciones de mezcla de la nueva medicación, Accera tenía razones para creer que Ensure™ llevó a estar disponible para todos los sujetos que estaban en el estudio en es el punto temporal o se inscribieron después del cambio.
Para evaluar si o no este cambio en las instrucciones en vez de la medicación del estudio parecía a aumentar la
15 tolerabilidad del producto, se realizó un análisis de las interrupciones del sujeto antes y después de realizar el cambio.
Interrupciones Antes del Cambio
20 Diez sujetos [9 de 31 (29,0 %) con Tratamiento y 1 de 27 (3,4 %) de placebo] interrumpieron el estudio. durante este periodo de tiempo, algunos sucesos dentro del sistema gastrointestinal fueron la causa principal de retirada del estudio. Dentro del sistema GI, 7 de 31 (22,6 %) sujetos con Tratamiento y 1 de 27 (3,4 %) sujetos con placebo interrumpieron el estudio debido a uno o más sucesos adversos.
25 Interrupciones Después del Cambio
Después del cambio de las instrucciones de mezcla de la medicación, la incidencia global de sucesos adversos que conducían a la interrupción del estudio disminuyó ligeramente en el grupo con el Tratamiento de un 29,0 % a un 21,9 %. De forma más notable, la incidencia de sucesos gastrointestinales que causaban la retirada del estudio en el
30 grupo con el Tratamiento disminuyó de un 22,6 % a un 12,5 %.
26

Claims (1)

  1. imagen1
    imagen2
ES13167176.0T 2007-07-31 2008-07-31 Uso de ensayo genómico y compuestos cetogénicos para tratamiento de una función cognitiva reducida Active ES2556535T3 (es)

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ES13167174.5T Active ES2556537T3 (es) 2007-07-31 2008-07-31 Uso de ensayo genómico y compuestos cetogénicos para tratamiento de una función cognitiva reducida
ES13167176.0T Active ES2556535T3 (es) 2007-07-31 2008-07-31 Uso de ensayo genómico y compuestos cetogénicos para tratamiento de una función cognitiva reducida
ES13167178.6T Active ES2556534T3 (es) 2007-07-31 2008-07-31 Uso de ensayo genómico y compuestos cetogénicos para tratamiento de una función cognitiva reducida
ES08796988.7T Active ES2608846T3 (es) 2007-07-31 2008-07-31 Uso de ensayos genómicos y compuestos cetogénicos para tratamiento de una función cognitiva reducida
ES13167177.8T Active ES2608286T3 (es) 2007-07-31 2008-07-31 Uso de ensayos genómicos y compuestos cetogénicos para tratamiento de una función cognitiva reducida

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