- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01119014
Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis (TEA)
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
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.
Study Overview
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
-
Aalborg, Denmark, 9000
- Aalborg Psychiatric Hospital
-
Copenhagen, Denmark, 2400
- Bispebjerg Hospital
-
Copenhagen, Denmark, 2100
- Psychiatric Centre Copenhagen, Rigshospitalet
-
Glostrup, Denmark, 2600
- Glostrup Hospital
-
Hillerød, Denmark, 3400
- Hillerød Hospital
-
Odense, Denmark, 5000
- Odense University Hospital
-
Risskov, Denmark, 8240
- Psychiatric Hospital for Children and Adolescents, Aarhus
-
Roskilde, Denmark, 4000
- Child and Adolescent Psychiatric Department, Region Zealand
-
Roskilde, Denmark, 4000
- Psychiatric Centre Sct. Hans
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Aripirazole
|
pill, 2,5-20 mg/day, maximum 16 weeks
|
Experimental: Quetiapine prolong
|
pill, 50-600mg/day, maximum 16 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Psychopathology: improvement on PANSS positive scale (PANSS 'Positive and Negative Syndrome Scale')
Time Frame: 12 weeks
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Psychopathology
Time Frame: 12 weeks
|
Psychopathology (other PANSS scales, DIPI, SGI-S, CGI-I,and GAPD).
|
12 weeks
|
Cognition
Time Frame: 12 weeks
|
Cognition and functioning (BACS Global Score, SCoRS-DK, Schizophrenia Cognition Rating Scale, BRIEF)
|
12 weeks
|
Adverse reactions
Time Frame: 12 weeks
|
Adverse reactions (UKU side effect scale, AIMS, SAS, BARS, and other adverse events)
|
12 weeks
|
Suicidal ideation
Time Frame: 12 weeks
|
Suicidal ideation (K-SADS-PL, specific questions for depressive disorders (current)
|
12 weeks
|
Genetic and antipsychotic laboratory tests
Time Frame: 12 weeks
|
Genetic variants affecting metabolism of antipsychotics
|
12 weeks
|
Prognostic factors
Time Frame: 12 weeks
|
Prognostic factors (DUP, and PAS)
|
12 weeks
|
Quality of Life
Time Frame: 52 weeks
|
Quality of Life (measured with Kidscreen)
|
52 weeks
|
Stigmatization
Time Frame: 52 weeks
|
Qualitative interviews
|
52 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Anne Katrine Pagsberg, MD, Ph.D., Bispebjerg Centre for Child and Adolescent Psychiatry. University of Copenhagen.
- Principal Investigator: Pia Jeppesen, MD, Ph.D., Glostrup Centre for Child and Adolescent Psychiatry. University of Copenhagen.
- Principal Investigator: Maj-Britt Lauritsen, MD, Hillerød Centre for Child and Adolescent Psychiatry.
- Principal Investigator: Per Hove-Thomsen, Professor, MD, D.M.Sci., Psychiatric Hospital for Children and Adolescents, Aarhus University Hospital.
- Principal Investigator: Marlene Briciet Lauritsen, MD., Child- and Adolescent Psychiatric Department, Aalborg.
- Principal Investigator: Niels Bilenberg, Professor, MD., Child and Adolescent Psychiatric Department, University of Southern Denmark, Odense
- Principal Investigator: Thomas Werge, Professor, Ph.D., Research Institute for Biological Psychiatry, Sct. Hans Hospital, Roskilde.
- Principal Investigator: Anders Fink-Jensen, MD, professor, DMSci., Psychiatric Centre Copenhagen. University of Copenhagen.
- Principal Investigator: Jesper Pedersen, MD., Psychiatric Hospital for Children and Adolescent; Region Zeeland
Publications and helpful links
General Publications
- Pagsberg AK, Krogmann A, Jeppesen P, von Hardenberg L, Klauber DG, Jensen KG, Rudå D, Decara MS, Jepsen JRM, Fagerlund B, Fink-Jensen A, Correll CU, Galling B. Early Antipsychotic Nonresponse as a Predictor of Nonresponse and Nonremission in Adolescents With Psychosis Treated With Aripiprazole or Quetiapine: Results From the TEA Trial. J Am Acad Child Adolesc Psychiatry. 2022 Aug;61(8):997-1009. doi: 10.1016/j.jaac.2021.11.032. Epub 2022 Jan 10.
- Jensen KG, Correll CU, Ruda D, Klauber DG, Decara MS, Fagerlund B, Jepsen JRM, Eriksson F, Fink-Jensen A, Pagsberg AK. Cardiometabolic Adverse Effects and Its Predictors in Children and Adolescents With First-Episode Psychosis During Treatment With Quetiapine-Extended Release Versus Aripiprazole: 12-Week Results From the Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis (TEA) Trial. J Am Acad Child Adolesc Psychiatry. 2019 Nov;58(11):1062-1078. doi: 10.1016/j.jaac.2019.01.015. Epub 2019 Mar 9.
- Jensen KG, Gartner S, Correll CU, Ruda D, Klauber DG, Stentebjerg-Olesen M, Fagerlund B, Jepsen JR, Fink-Jensen A, Juul K, Pagsberg AK. Change and dispersion of QT interval during treatment with quetiapine extended release versus aripiprazole in children and adolescents with first-episode psychosis: results from the TEA trial. Psychopharmacology (Berl). 2018 Mar;235(3):681-693. doi: 10.1007/s00213-017-4784-5. Epub 2017 Nov 29.
- Pagsberg AK, Jeppesen P, Klauber DG, Jensen KG, Ruda D, Stentebjerg-Olesen M, Jantzen P, Rasmussen S, Saldeen EA, Lauritsen MG, Bilenberg N, Stenstrom AD, Nyvang L, Madsen S, Werge TM, Lange T, Gluud C, Skoog M, Winkel P, Jepsen JRM, Fagerlund B, Correll CU, Fink-Jensen A. Quetiapine extended release versus aripiprazole in children and adolescents with first-episode psychosis: the multicentre, double-blind, randomised tolerability and efficacy of antipsychotics (TEA) trial. Lancet Psychiatry. 2017 Aug;4(8):605-618. doi: 10.1016/S2215-0366(17)30166-9. Epub 2017 Jun 7.
- Jensen KG, Correll CU, Ruda D, Klauber DG, Stentebjerg-Olesen M, Fagerlund B, Jepsen JRM, Fink-Jensen A, Pagsberg AK. Pretreatment Cardiometabolic Status in Youth With Early-Onset Psychosis: Baseline Results From the TEA Trial. J Clin Psychiatry. 2017 Sep/Oct;78(8):e1035-e1046. doi: 10.4088/JCP.15m10479.
- Pagsberg AK, Jeppesen P, Klauber DG, Jensen KG, Ruda D, Stentebjerg-Olesen M, Jantzen P, Rasmussen S, Saldeen EA, Lauritsen MB, Bilenberg N, Stenstrom AD, Pedersen J, Nyvang L, Madsen S, Lauritsen MB, Vernal DL, Thomsen PH, Paludan J, Werge TM, Winge K, Juul K, Gluud C, Skoog M, Wetterslev J, Jepsen JR, Correll CU, Fink-Jensen A, Fagerlund B. Quetiapine versus aripiprazole in children and adolescents with psychosis--protocol for the randomised, blinded clinical Tolerability and Efficacy of Antipsychotics (TEA) trial. BMC Psychiatry. 2014 Jul 11;14:199. doi: 10.1186/1471-244X-14-199.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Schizophrenia Spectrum and Other Psychotic Disorders
- Psychotic Disorders
- Mental Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Agents
- Antidepressive Agents
- Dopamine Agonists
- Dopamine Agents
- Serotonin 5-HT1 Receptor Agonists
- Serotonin Receptor Agonists
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin Antagonists
- Dopamine D2 Receptor Antagonists
- Dopamine Antagonists
- Aripiprazole
- Quetiapine Fumarate
Other Study ID Numbers
- TEAprotocolversion5-11 03 2010
- 2009-016715-38 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Psychosis
-
Icahn School of Medicine at Mount SinaiNational Institute of Mental Health (NIMH)RecruitingFirst Episode Psychosis (FEP) | Clinical High Risk for Psychosis (CHR)United States
-
University of UdineNational Research Council (CNR), Institute of Biomolecular Chemistry (ICB)...RecruitingClinical High Risk for Psychosis | Ultra High Risk for Psychosis | Attenuated Psychotic SymptomsItaly
-
University of New MexicoNational Institute of Mental Health (NIMH)CompletedPsychosis | Clinical High Risk for Psychosis | First Episode PsychosisUnited States
-
Shanghai Jiao Tong University School of MedicineGuangzhou Psychiatric Hospital; Suzhou Psychiatric Hospital; Tianjin Anding Hospital and other collaboratorsRecruitingSchizophrenia; Psychosis | Clinical High Risk | First Episode PsychosisChina
-
Chulalongkorn UniversityNational Research Council of Thailand; Thanyarak InstituteCompletedMethamphetamine-induced PsychosisThailand
-
University of California, San DiegoCenter for Medicinal Cannabis ResearchRecruitingEarly PsychosisUnited States
-
Yale UniversityCompleted
-
University of TorontoUniversity of British Columbia; Centre for Addiction and Mental Health; Queen... and other collaboratorsNot yet recruitingPsychotic Disorders | Schizophrenia | Psychosis | Schizophrenia; Psychosis
-
Northwell HealthNational Institute of Mental Health (NIMH)RecruitingFirst Episode PsychosisUnited States
-
State reference center for psychosocial careUniversity of ValenciaCompleted
Clinical Trials on Aripiprazole
-
National Institute on Alcohol Abuse and Alcoholism...Brown UniversityCompleted
-
Otsuka Beijing Research InstituteCompleted
-
H. Lundbeck A/SOtsuka Pharmaceutical Co., Ltd.CompletedSchizophreniaUnited States
-
University of California, Los AngelesAlkermes, Inc.TerminatedSchizophrenia | Schizophreniform Disorder | Schizoaffective Disorder, Depressive TypeUnited States
-
Otsuka Pharmaceutical Co., Ltd.CompletedMajor Depressive DisorderJapan
-
Veterans Medical Research FoundationBristol-Myers SquibbCompleted
-
Otsuka Pharmaceutical Co., Ltd.CompletedSchizophreniaJapan
-
Otsuka Pharmaceutical Development & Commercialization...CompletedSchizophreniaKorea, Republic of, United States, Estonia, Italy, Hungary, Bulgaria, Croatia, France, Poland, Thailand, Puerto Rico, Chile, South Africa, Austria, Belgium
-
Alkermes, Inc.CompletedSchizophreniaUnited States
-
Alkermes, Inc.CompletedSchizophreniaUnited States