Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis

Psychosis Clinical Trial

— TEA  

Official title:

Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis- An Investigator-initiated, Phase IV, Randomised Double-blind Multi-centre Trial of the Benefits and Harms of Aripiprazole Versus Quetiapine in Children and Adolescents With Psychosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01119014
• Other study ID #: TEAprotocolversion5-11 03 2010
• Secondary ID: 2009-016715-38
• Status: Active, not recruiting
• Phase: Phase 4
• First received: May 3, 2010
• Last updated: October 2, 2014
• Start date: May 2010
• Est. completion date: July 2015

Study information

• Verified date: October 2014
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines AgencyDenmark: The Danish National Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

The benefits and harms of antipsychotics are relatively well studied in adults. However, there is a lack of scientifically valid studies regarding the benefits and harms of antipsychotics in children and adolescents with psychosis.

The main objective of the TEA trial is to compare the efficacy and adverse reactions of two antipsychotics (quetiapine versus aripiprazole) in children and adolescents between 12-17 years of age with psychotic symptoms on psychopathology, cognitive deficits, and daily functioning. Furthermore, the trial will focus on adverse reaction profiles of the two antipsychotics as well as early predictors of later sustained clinical effects of these antipsychotics.

Description:

A sex and age matched healthy control group will be included to form a reference group for cognitive and somatic measures. The healthy controls will not receive any trial medication.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: July 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 12 Years to 17 Years

Eligibility

Patients - Inclusion Criteria:

• 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. The maximum accepted previous treatment with antipsychotic compounds is two weeks cumulatively, and during the two weeks prior to inclusion no continuous treatment and a maximum of four dosages in total can have been received.

• Somatic illness: No somatic contraindication to planned medication, documented by standard somatic examination

• Written informed consent.

Patients - Exclusion Criteria:

• 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)

• 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.

Healthy volunteers - Inclusion Criteria:

• Matching: Healthy controls (n=100) are included, in the way that they are matched to the first 100 patients included in the study (i.e., corresponding to the number of patients required in each treatment group). They will be matched according to:

• age;

• sex; and

• socioeconomic status (based on a combination of parental education and income, according to criteria from the National Institute of Public Health (earlier Danish Institute of Clinical Epidemiology, DIKE)).

• Informed consent.

Healthy volunteers - Exclusion Criteria:

• Psychopathology: People with a previous psychotic disorder (ICD 10, F20-F29 and F30.2, F31.2, F31.5, F32.3 and F33.3) or current psychiatric disorder (multiaxial axis 1) are not included. This is verified by diagnostic screening using K-SADS-PL at eligibility assessment before inclusion into the study of healthy controls. The presence of psychotic psychiatric diagnoses in first-degree relatives is also a cause for exclusion.

• Somatic illnesses: People with severe chronic somatic illness or a history of severe head-trauma are not included.

• Intelligence: People with known mild mental retardation (i.e., IQ between 50-70) prior to inclusion are excluded; however, if mild mental retardation is found during the study, participants are not excluded, since they must be considered a marginal part of the normal distribution. People with moderate to severe mental retardation (i.e., IQ < 50) are excluded.

• Substance abuse: People with severe alcohol- or drug abuse are excluded. 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. Brief periods of large alcohol/cannabis intake are not a cause of exclusion from the study; however, cognitive and other examinations are not carried out while participants are under the influence.

• Lack of informed consent.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Mental Disorders
• Psychosis
• Psychotic Disorders

Intervention

Drug:
• Aripiprazole
pill, 2,5-20 mg/day, maximum 16 weeks
• Quetiapine
pill, 50-600mg/day, maximum 16 weeks

Locations

Country	Name	City	State
Denmark	Aalborg Psychiatric Hospital	Aalborg
Denmark	Bispebjerg Hospital	Copenhagen
Denmark	Psychiatric Centre Copenhagen, Rigshospitalet	Copenhagen
Denmark	Glostrup Hospital	Glostrup
Denmark	Hillerød Hospital	Hillerød
Denmark	Odense University Hospital	Odense
Denmark	Psychiatric Hospital for Children and Adolescents, Aarhus	Risskov
Denmark	Child and Adolescent Psychiatric Department, Region Zealand	Roskilde
Denmark	Psychiatric Centre Sct. Hans	Roskilde

Sponsors (11)

Lead Sponsor

Collaborator

Anne Katrine Pagsberg

Albert Einstein College of Medicine of Yeshiva University, Allocated inheritance from Elizabeth Stevn and Niels Rindom, Denmark, AP Moeller Foundation, Capital Region Pharmacy, Denmark, Copenhagen Trial Unit, Center for Clinical Intervention Research, Psychiatric Centre Copenhagen, Denmark, Research Institute for Biological Psychiatry, Sct. Hans Hospital, Denmark, The Psychiatric Centre for Children and Adolescents in Bispebjerg, Denmark, The Research Council for Health and Disease, Denmark, Tryg Fonden, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Psychopathology: improvement on PANSS positive scale (PANSS 'Positive and Negative Syndrome Scale')		12 weeks	No
Secondary	Psychopathology	Psychopathology (other PANSS scales, DIPI, SGI-S, CGI-I,and GAPD).	12 weeks	No
Secondary	Cognition	Cognition and functioning (BACS Global Score, SCoRS-DK, Schizophrenia Cognition Rating Scale, BRIEF)	12 weeks	No
Secondary	Adverse reactions	Adverse reactions (UKU side effect scale, AIMS, SAS, BARS, and other adverse events)	12 weeks	Yes
Secondary	Suicidal ideation	Suicidal ideation (K-SADS-PL, specific questions for depressive disorders (current)	12 weeks	Yes
Secondary	Genetic and antipsychotic laboratory tests	Genetic variants affecting metabolism of antipsychotics	12 weeks	No
Secondary	Prognostic factors	Prognostic factors (DUP, and PAS)	12 weeks	No
Secondary	Quality of Life	Quality of Life (measured with Kidscreen)	52 weeks	No
Secondary	Stigmatization	Qualitative interviews	52 weeks	No