E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Individuals at Ultra High Risk for Psychosis |
Sujetos con alto riesgo para la psicosis |
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E.1.1.1 | Medical condition in easily understood language |
Adolescents who are at risk for developing psychosis. |
Adolescentes con alto riesgo para la psicosis |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
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 |
To compare transition rates to psychosis during 2 years of follow-up between the omega-3 fatty acids arm and the placebo arm in adolescent subjects who are at risk for developing psychosis. Starting point is the first administration of study medication at the end of visit 2. Endpoint is the moment that a UHR subject makes a transition to psychosis according to the CAARMS criteria, over a period of 2 years. |
Comparar la tasa de transición a trastorno psicótico durante 2 años de seguimiento entre individuos que están en riesgo a desarrollar una psicosis (SRP) que toman ácidos grasos omega-3 versus los individuos en riesgo de psicosis que toman placebo. El punto de inicio es la primera administración de la medicación del estudio al final de la visita 2. La variable es el momento en el cual los sujetos en riesgo a desarrollar una psicosis realizan la transición a psicosis de acuerdo a los criterios de la escala CAARMS |
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E.2.2 | Secondary objectives of the trial |
1. Discontinuation rates - comparison between the two arms
2. Tolerability - comparison between the two treatment arms
3. Symptomatology - comparison between the two treatment arms
4. Psychosocial and cognitive function - comparison between the two treatment arms
5. Quality of life - comparison between the two treatment arms
6. Bloodlevels of bioactive lipids - comparison between the two treatment arms
7. (epi)genetic markers - comparison between the two treatment arms
8. Brain structure and function - comparison between the two treatment arms as measured wit Magnetic Resonance Imaging (MRI)
9. Assess the value of MRI and blood parameters as predictive measures for clinical response. |
1.Tasa de discontinuidad- Comparación entre las 2 ramas.
2.Tolerabilidad- Comparación entre las 2 ramas.
3.Sintomatología- Comparación entre las 2 ramas.
4.Funcionamiento psicosocial y funcionamiento cognitivo- Comparación entre las 2 ramas.
5.Calidad de vida- Comparación entre las 2 ramas.
6.Niveles de sangre de lípidos bioactivos- Comparación entre las 2 ramas.
7.Marcadores epigenéticos- Comparación entre las 2 ramas.
8.Estructura y la función cerebral: Comparación entre las 2 ramas y mesuradas mediante imágenes de resonancia magnética (IRM).
9.Búsqueda de potenciales biomarcadores (IRM i parámetros en sangre) que puedan predecir la respuesta clínica de los sujetos en riesgo de psicosis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Written informed consent of the subject. For individuals younger than 18 years of age the parents / legal representatives need to give consent, and the subject can provide assent (whether the latter is required depends on local laws and regulations).
-UHR diagnosis as made using the Comprehensive Assessment of At-Risk Mental States (CAARMS) (Yung et al., 2005). Subjects have to meet one or more of the following criteria: (a) attenuated psychotic symptoms, (b) brief limited intermittent psychotic symptoms (a history of one or more episodes of frank psychotic symptoms that resolved spontaneously within 1 week in the past year), or (c) either the presence of schizotypal personality disorder or a family history of psychosis in a first-degree relative, all three together with a recent decline in function. |
-Que tengan el consentimiento informado firmado. Para los sujetos menores a 18 años deberán firmar el consentimiento informado sus padres o tutores legales. Los pacientes deberán firmar un asentimiento informado.
-Que cumplan con los criterios definidos para el riesgo de psicosis evaluados mediante la entrevista Comprehensive Assessment of At-Risk Mental States (CAARMS, Yung et al 2005). Los sujetos tienen que cumplir uno o más de los siguientes criterios: (a) Síntomas psicóticos atenuados, (b) síntomas psicóticos breves e intermitentes, (c) presentar o bien un trastorno de personalidad esquizotipica o bien tener historia de psicosis en un familiar de primer grado, todos ellos acompañados por una reciente disminución en la funcionalidad. |
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E.4 | Principal exclusion criteria |
•Any clinically significant medical condition that may influence the results of the trial or affect the ability to take part in a trial.
•Laboratory screening values considered clinically relevant by a medical doctor for transaminases, thyroid hormones or coagulation parameters
•Current or past DSM-IV diagnosis of psychosis, as measured with K-SADS-PL
•Current treatment with an antipsychotic or mood-stabilising agent
•Intake of an antipsychotic or mood-stabilising agent in the two weeks prior to study inclusion
•Intake of an antipsychotic agent equivalent to a total haloperidol use of >50 mg in the six months prior to study inclusion
•UHR diagnosis on the basis of attenuated psychotic symptoms that are entirely explained by acute intoxication
•Current aggression or dangerous behaviour (PANSS G14 score 5 or above)
•Current suicidality / self-harm (PANSS G6 score 7)
•Current DSM-IV diagnosis of alcohol or substance dependence as measured with K-SADS-PL
•Any current or previous neurological disorder, including epilepsy
•History of head injury resulting in unconsciousness lasting at least 1 hour
•IQ < 70
•More than 4 weeks of regular omega-3 supplementation (>2 daily capsules standard strength providing >600 mg combined EPA/DHA) within the last 6 months. |
-Cualquier condición médica que pueda influenciar en los resultados del ensayo clínico.
-Valores del cribaje de laboratorio considerados clínicamente significantes por un doctor para transaminasas, hormonas tiroideas o parámetros de coagulación.
-Poseer algún diagnostico presente o pasado de psicosis, según criterios DSM-IV.
-Estar en tratamiento antipsicótico o un estabilizador del estado de ánimo.
-Toma de antipsicóticos o estabilizadores del estado de ánimo en las dos semanas anteriores al inicio del estudio.
-Haber tomado antipsicóticos equivalente a una dosis de haloperidos mayor a 50 mg en los seis meses previos al estudio.
-Que los síntomas SRP solo aparezcan en el contexto de una intoxicación aguda.
-Comportamiento agresivo o peligroso (puntuación de 5 o más en el ítem G14 de la PANSS)
-Conductas suicidas o autolesiones (ítem G6 de la PANSS puntuación de 7)
-Diagnostico actual de dependencia de alcohol o substancias medido con la entrevista K-SADS-PL
-Cualquier diagnóstico actual o previo de trastorno neurológico, incluyendo epilepsia
-Historia de traumatismo craneoencefálico con pérdida de conciencia de como mínimo 1 hora.
-CI<70
-Más de 4 semanas de toma de suplemento regular con omega-3 (>2 cápsulas diarias que proporcionen una combinación de >600 mg de EPA/DHA). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The moment that a UHR subject makes a transition to psychosis according to the CAARMS criteria. |
Momento en el cual los sujetos en riesgo a desarrollar una psicosis realizan la transición a psicosis de acuerdo a los criterios de la escala CAARMS |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The endpoint will evaluated at each study visit. |
La variable será medida en cada visita del estudio |
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E.5.2 | Secondary end point(s) |
1. Discontinuation rate
[Time Frame: 2 years] [Safety Issue: No]
Comparison between the two arms
2. Tolerability
[Time Frame: 2 years] [Safety Issue: No]
Comparison between the two treatment arms
3. Symptomatology
[Time Frame: 2 years] [Safety Issue: No]
Comparison between the two treatment arms
4. Psychosocial and cognitive function
[Time Frame: 2 years] [Safety Issue: No]
Comparison between the two treatment arms
5. Quality of life
[Time Frame: 2 years] [Safety Issue: No]
Comparison between the two treatment arms
6. Bloodlevels of bioactive lipids
[Time Frame: 2 years] [Safety Issue: No]
Comparison between the two treatment arms
7. (epi)genetic markers
[Time Frame: 2 years] [Safety Issue: No]
Comparison between the two treatment arms
8. Brain structure and function
[Time Frame: 2 years] [Safety Issue: No]
Comparison between the two treatment arms as measured with Magnetic Resonance Imaging (MRI)
9. MRI and blood parameters
[Time Frame: 2 years] [Safety Issue: No]
The ability of MRI and blood parameters to serve as potential biomarkers that may predict clinical response |
1. Tasa de discontinuidad
(Periodo de tiempo: 2 años, Incidente de seguridad: No)
Comparación entre las 2 ramas.
2.Tolerabilidad
(Periodo de tiempo: 2 años, Incidente de seguridad: No)
Comparación entre las 2 ramas.
3.Sintomatología
(Periodo de tiempo: 2 años, Incidente de seguridad: No)
Comparación entre las 2 ramas.
4.Funcionamiento psicosocial y funcionamiento cognitivo
(Periodo de tiempo: 2 años, Incidente de seguridad: No)
Comparación entre las 2 ramas.
5.Calidad de vida
(Periodo de tiempo: 2 años, Incidente de seguridad: No)
Comparación entre las 2 ramas.
6.Niveles de sangre de lípidos bioactivos
(Periodo de tiempo: 2 años, Incidente de seguridad: No)
Comparación entre las 2 ramas.
7.Marcadores epigenéticos
(Periodo de tiempo: 2 años, Incidente de seguridad: No)
Comparación entre las 2 ramas.
8.Estructura y la función cerebral:
(Periodo de tiempo: 2 años, Incidente de seguridad: No)
Comparación entre las 2 ramas y mesuradas mediante imágenes de resonancia magnética (IRM).
9. IRM y parámetros en sangre:
(Periodo de tiempo: 2 años, Incidente de seguridad: No)
Potenciales biomarcadores que pueden predecir la respuesta clínica de los sujetos en riesgo de psicosis. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of the study, the subject sample will be grouped into those who made the transition versus those who did not make the transition to psychosis. The secondary endpoints will be compared at each available timepoint between the 2 groups. |
Al final del estudio, la muestra objeto se agruparán en los que han hecho la transición en comparación con los que no hacen la transición a la psicosis. Los criterios de valoración secundarios se compararon en cada punto disponible entre los 2 grupos. |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
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) | No |
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 | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Controles sanos |
Healthy controls |
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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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Germany |
Israel |
Italy |
Netherlands |
Norway |
Spain |
Switzerland |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
|
For each subject, participating in the trial ends when a transition to psychosis is made, as confirmed through the CAARMS. This moment of transition can take place any time between shortly after the start of the trial up until the end of the 2-years follow-up period. |
La participación de cada sujeto finaliza cunado la transición ha psicosis se ha realizado según la escala CAARMS. Dicho momento de transición puede darse en cualquier momento desde el inicio del ensayo o final del mismo en los 2 años de seguimiento. |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |