| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| non-organic and non-drug-induced psychosis, meeting the criteria for ICD-10 diagnoses: F20, F22-F29 and F30.2, F31.2, F31.5, F32.3 and F33.3. |
|
| E.1.1.1 | Medical condition in easily understood language |
| non-organic and non-drug-induced psychosis |
|
| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10032314 |
| E.1.2 | Term | Other nonorganic psychoses |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10039626 |
| E.1.2 | Term | Schizophrenia |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10004916 |
| E.1.2 | Term | Bipolar affective disorder, depressed, severe degree, specified as with psychotic behavior |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025460 |
| E.1.2 | Term | Major depressive disorder, recurrent episode, severe degree, specified as with psychotic behaviour |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10039621 |
| E.1.2 | Term | Schizoaffective disorder |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025468 |
| E.1.2 | Term | Major depressive disorder, single episode, severe degree, specified as with psychotic behavior |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10046122 |
| E.1.2 | Term | Unspecified psychosis |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10026780 |
| E.1.2 | Term | Manic psychosis |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10012255 |
| E.1.2 | Term | Delusional disorder, unspecified type |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10051988 |
| E.1.2 | Term | Acute and transient psychotic disorder |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10004924 |
| E.1.2 | Term | Bipolar affective disorder, manic, severe degree, specified as with psychotic behavior |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| 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 |
Examine the efficacy of antipsychotics in children and adolescents between 12-17 years of age with psychosis; the effect is measured as:
a. psychopathology, primary outcome measure of interest: Severity of psychotic symptoms (PANSS positive subscale);
b. cognitive deficits, primary outcome measure of interest: Global BACS cognitive score;
c. cognitive daily functioning, primary outcome measure of interest: Global executive function, SCoRS-DK.
Examine the tolerability of antipsychotics in children and adolescents between 12-17 years of age with psychosis, concerning:
a. motor adverse reactions;
b. metabolic adverse reactions;
c. hormonal adverse reactions;
d. cardiac adverse reactions;
e. other side effects, including psychological
|
|
| E.2.2 | Secondary objectives of the trial |
Identify early indicators (after 2 and 4 weeks of treatment with two different atypical antipsychotics) of sustained clinically significant effects on psychopathology assessed after 12 weeks and after one year after inclusion into the trial.
Additionally, we will investigate health-related quality of life after antipsychotic treatment for psychosis, and the perception of stigmatisation following a psychotic illness.
Additionally, we will examine primary and secondary motion patterns and the development of aripiprazole- or quetiapine-induced, secondary motion patterns using KinectTM (Microsoft Xbox) and Kinect Windows Software Development Kit.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients:
• Diagnosis: Children and adolescents with a non-organic and non-drug-induced psychosis, meeting the criteria for ICD-10 diagnoses: F20, F22-F29 and F30.2, F31.2 F31.5, F32.3 and F33.3. This is verified with a semi-structured psychopathological interview using K-SADS-PL (Kaufmann 1997) four weeks after inclusion into the trial.
• Psychopathology: Children and adolescents with psychotic symptoms, scoring ≥ 4 on at least one of the following PANSS items: P1 (delusions), P2 (conceptual disorganisation), P3 (hallucinations), P5 (grandiosity), P6 (suspiciousness/persecution) or G9 (unusual thought content); and a total PANSS score > 60. The treating physician has decided to prescribe an antipsychotic compound.
• Age: 12-17 years (both inclusive).
• Sex: Both sexes are included.
• Previous treatment: Patients must be antipsychotic-naïve or only have received a limited amount of treatment with antipsychotics previously. As a maximum, the treatment with antipsychotics for a psychotic illness must have been within the previous calendar year, or, maximum one week’s treatment (lifetime, regardless of time).
• Somatic illness: No somatic contraindication to planned medication, documented by standard somatic examination
• Written informed consent. |
|
| E.4 | Principal exclusion criteria |
Patients:
• Compulsory treatment: Patients that are compulsorily hospitalised against their will are excluded. If their status changes to voluntary hospitalisation, patients can be included. If the patient is already included in the trial and is briefly detained, confined, or subjected to other forceful treatment according to the Danish Psychiatric Care Act (‘Psykiatriloven’), both the patient and parents have to agree to remain in the trial if exclusion is to be avoided. Compulsory treatment in the form of, e.g., brief forced immobilisation or single instances of forced medication, are not causes for exclusion.
• Diagnoses: Patients with drug-induced or organic psychosis, severe chronic somatic illness, or a history of severe head-trauma are not included. Patients that do not have psychotic symptoms but are prescribed antipsychotic treatment on the indication of, e.g., severe behavioural problems or tics are not included.
• Pregnancy: Pregnant or lactating patients are not included (a pregnancy test is undertaken at inclusion). Female participants, that are sexually active, must use safe contraception throughout the trial period (see section 6.4). A pregnancy test (urine sample) is also taken throughout the trial if suspicion of pregnancy is present, e.g., if the participant is changing status from not sexually active to sexually active.
• Substance abuse: People with severe alcohol or drug abuse are not included. Possible abuse is monitored both by interviewing participants and by taking a urine sample at inclusion and at 4, 12 and 52 weeks follow-up (if there is suspicion of substance abuse), testing for the presence of cocaine, amphetamine, cannabis, opiates, metamfetamine (inclusive for extacy), and benzodiazepines. When severe abuse is suspected during the trial, an ad hoc urine sample is taken. Brief periods of large alcohol/cannabis intake are not a cause of exclusion from the trial; however, cognitive and other examinations are not carried out while patients are under the influence of drugs or alcohol.
• Aggravation: Patients may be excluded if there is a significant worsening of clinical state during the course of the trial (i.e., increases of 30% or more from baseline on the PANSS total score).
• Allergy and intolerance: Patients with allergy towards the investigational drugs, or is lactose intolerant are not included.
• Lack of informed consent.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Psychopathology: PANSS positive scale (PANSS ‘Positive and Negative Syndrome Scale’) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
primary timepoint 12 weeks
2, 4, 12, and 52 weeks |
|
| E.5.2 | Secondary end point(s) |
Psychopathology
• Other PANSS scales (negative scale and general symptoms)
• DIPI (Dimensions of Psychosis Instrument) (Mizrahi et al., 2006);
• CGI-S (Clinical Global Impression Severity) (Guy, 1976);
• CGI-I (Clinical Global Impression Improvement) (Guy, 1976);
• CGI-Efficacy (Clinical Global Impression Efficacy) (Guy, 1976)
• GAPD (Global Assessment of Psychosocial Disability) (World Health Organization, 1993).
Cognition
• Cognition: BACS Global Score (Brief Assessment of Cognition in Schizophrenia) (Keefe et al., 2004);
• Cognitive daily functioning: Global functioning from SCoRS-DK (Schizophrenia Cognition Rating Scale, Danish version) (Keefe et al., 2006);
• Global executive functioning measured with BRIEF (Behavioural Rating Inventory of Executive Functions) (Gioia, G.A. 2005).
• Other secondary outcomes are attention, executive functions and memory from BACS as well as specific sub-outcomes from SCoRS-DK and BRIEF.
Adverse reactions
• UKU side effect scale (‘Udvalget for Kliniske Undersøgelser’ Side Effect Rating Scale) (Lingjaerde et al., 1987);
• AIMS (Abnormal Involuntary Movement Scale) (Guy W., 1976);
• SAS (Simpson Angus Scale) (Simpson and Angus, 1970);
• BARS (Barens Akathisia Rating Scale) (Barnes T.R.E., 1989);
• KinectTM- based instrument
• Other adverse events, i.e., any untoward occurrences including:
o cardiac adverse reactions effects such as prolonged QT- interval
o somatic events (blood pressure, pulse, weight, height, BMI and abdominal circumference); and
o abnormal laboratory test results (lipid status, metabolic changes, other general blood tests according to clinical guidelines for clinical practice, and ECG).
Suicidal ideation
• K-SADS-PL, specific questions for depressive disorders (current) recurring thought of death, suicidal thoughts, suicidal action level of serious, suicidal action level of life-threatening, non-suicidal physical self-inflicted harm.
Genetic and antipsychotic laboratory tests
• determination of serum concentration of antipsychotics;
• clinical genetic analysis, including analysis of genetic variants affecting metabolism of antipsychotics;
• offering of participation in the project ”Arv og Miljø” for genetic analyses that is not included in the clinical genetic analysis.
Prognostic factors
• DUP (Duration of Untreated Psychosis) (see below for references);
• PAS (Premorbid Adjustment Scale) (see below for references).
Quality of life and stigma
• KIDSCREEN-52
• Experiences with the Stigma of Mental Illness
• Selected questions from TeenSEMI
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
primary timepoint 12 weeks
2, 4, 12, and 52 weeks |
|
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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
| 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 | 7 |
| 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 | Information not present in EudraCT |
| 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
|
| The last follow-up of the last participant at week 52 after randomisation is considered as end of trial |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| 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 |
Print
