Bergen Psychosis Project 2 - The Best Intro Study (BP2)

Bergen Psychosis Project 2 - The Bergen-Stavanger-Innsbruck-Trondheim Study

In the Bergen Psychosis Project 2 the antipsychotic drugs aripiprazole, amisulpride, and olanzapine will be compared head-to-head in patients with schizophrenia and related psychoses and followed for 12 months. The study is independent of the pharmaceutical industry, and in accordance with a pragmatic design a clinically relevant sample will be included with as few exclusion criteria as possible. The patients will be assessed repeatedly with regards to symptoms, side effects, and cognitive functioning, as well as laboratory parameters. The study hypothesis is that clinically meaningful differences among the drugs will be disclosed in a pragmatic design.

Study Overview

• Status: Completed
• Conditions: Psychotic Disorders; Schizophrenia
• Intervention / Treatment: Drug: Amisulpride; Drug: Aripiprazole; Drug: Olanzapine

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Medizinische Universität Innsbruck
• Norway
  • Bergen, Norway, 5223
    • Haukeland University Hospital
  • Stavanger, Norway
    • Stavanger University Hospital
  • Trondheim, Norway
    • St. Olavs Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

A:The observational cohort

• Patients 16 years old or older
• Active psychosis as determined by a score of 4 or more on one or more of the items Delusions, Hallucinatory behavior, Grandiosity, Suspiciousness/ persecution, or Unusual thought content in the Positive and Negative Syndrome Scale (PANSS).
• Or ICD-10 diagnosis corresponding to psychotic disorders or other mental disorders with psychotic features (F10-F19: .5 (psychotic disorder); F20-F29, F30.2, F31.2, F31.5, F32.3, F33.3). From which eligible patients are recruited to the B:The pragmatic, randomized, controlled trial (The Best Intro Study)
• Patients 18 years and older
• Schizophrenia spectrum and delusional disorder
• Symptoms of psychosis as determined by a score of 4 or more on one or more of the items Delusions, Hallucinatory behavior, Grandiosity, Suspiciousness/ persecution, or Unusual thought content in the Positive and Negative Syndrome Scale (PANSS).

Exclusion Criteria:

• Inability to understand spoken Norwegian.
• Patients with organic psychosis due to limbic encephalitis detected by antibodies in serum obtains at inclusion (such as NMDAR, VGKC and paraneoplastic antibodies performed at the Neuroimmunology Laboratory, Department of Neurology, Haukeland University Hospital) Pregnant or breast feeding women.
• Aripiprazole: Hypersensitivity to the active substance or to any of the excipients
• Amisulpride: Hypersensitivity to the active ingredient or to other ingredients of the medicinal product; concomitant prolactin-dependent tumours e.g. pituitary gland prolactinomas and breast cancer; phaeochromocytoma; lactation, combination with the following medications which could induce torsade de pointes: Class Ia antiarrhythmic agents such as quinidine, disopyramide, procainamide. Class III antiarrhythmic agents such as amiodarone, sotalol. Other medications such as bepridil, cisapride, sultopride, thioridazine, methadone, IV erythromycin, IV vincamine, halofantrine, pentamidine, sparfloxacin. Combinations with levodopa.
• Olanzapine: Hypersensitivity to the active substance or to any of the excipients. Patients with known risk of narrow-angle glaucoma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Olanzapine	Drug: Olanzapine; Tablets, dose range 2.5-20 mg/ day; Other Names: Zyprexa
Active Comparator: Aripiprazole	Drug: Aripiprazole; Tablets, dose range 5-30 mg/ day; Other Names: Abilify
Active Comparator: Amisulpride	Drug: Amisulpride; Tablets, dose range 50-1200 mg/ day; Other Names: Solian

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change of the Positive and Negative Syndrome Scale total score	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of waist circumference		12 months
Change of the positive subscale scores of the Positive and Negative Syndrome Scale		12 months
Change of the negative subscale scores of the Positive and Negative Syndrome Scale		12 months
Change of the general subscale scores of the Positive and Negative Syndrome Scale		12 months
Change of the Global Assessment of Functioning scale		12 months
Change of the Clinical Global Impression - Severity of Illness score		12 months
Change of the UKU Side Effects Rating Scale - Patient version score		12 months
Change of serum High Density lipoprotein		12 months
Change of serum Low Density lipoprotein		12 months
Change of serum total cholesterols		12 months
Change of serum triglycerides		12 months
Change of serum fasting glucose		12 months
Change of prolactin		12 months
Change of the rate-corrected QT interval at electrocardiogram		12 months
Change of body mass index	body weight in kilograms divided by the squared height in metres	12 months
Change of hip circumference		12 months
Change of systolic blood pressure		12 months
Change of diastolic blood pressure		12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of cognitive functions		12 months
Change of mood symptoms		12 months
Change of brain functional measures	Based on functional MRI - explorative	12 months
Change of brain structural measures	Based on structural MRI - explorative	12 months
Change of inflammatory markers in blood		12 months
Change of gene expression in blood		12 months
Change of bone turnover markers in serum		12 months
Change of motor activity	Measured by actigraph	12 months
Change of autonomic activity	Measured by actiheart	12 months

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Collaborators: Helse Vest
• Investigators: Principal Investigator: Erik Johnsen, M.D., Ph.D., Haukeland University Hospital

Publications and helpful links

General Publications

• Fathian F, Gjestad R, Kroken RA, Loberg EM, Reitan SK, Fleichhacker WW, Rettenbacher M, Larsen TK, Joa I, Stabell LA, Kjelby E, Sinkevicute I, Alisauskiene R, Steen VM, Johnsen E. Association between C-reactive protein levels and antipsychotic treatment during 12 months follow-up period after acute psychosis. Schizophr Res. 2022 Mar;241:174-183. doi: 10.1016/j.schres.2022.01.049. Epub 2022 Feb 4.
• Hoekstra S, Bartz-Johannessen C, Sinkeviciute I, Reitan SK, Kroken RA, Loberg EM, Larsen TK, Rettenbacher M, Johnsen E, Sommer IE. Sex differences in antipsychotic efficacy and side effects in schizophrenia spectrum disorder: results from the BeSt InTro study. NPJ Schizophr. 2021 Aug 18;7(1):39. doi: 10.1038/s41537-021-00170-3.
• Johnsen E, Kroken RA, Loberg EM, Rettenbacher M, Joa I, Larsen TK, Reitan SK, Walla B, Alisauskiene R, Anda LG, Bartz-Johannessen C, Berle JO, Bjarke J, Fathian F, Hugdahl K, Kjelby E, Sinkeviciute I, Skrede S, Stabell L, Steen VM, Fleischhacker WW. Amisulpride, aripiprazole, and olanzapine in patients with schizophrenia-spectrum disorders (BeSt InTro): a pragmatic, rater-blind, semi-randomised trial. Lancet Psychiatry. 2020 Nov;7(11):945-954. doi: 10.1016/S2215-0366(20)30341-2.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: October 3, 2011
• First Submitted That Met QC Criteria: October 4, 2011
• First Posted (Estimate): October 5, 2011

Study Record Updates

• Last Update Posted (Actual): June 19, 2020
• Last Update Submitted That Met QC Criteria: June 17, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Translational Research; Treatment Effectiveness; Antipsychotic Drugs
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mental Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; 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; Antidepressive Agents, Second-Generation; Olanzapine; Aripiprazole; Amisulpride
• Other Study ID Numbers: 2010/3387; 11/01070 (Other Identifier: The Norwegian Medicines Agency); 2010-022307-22 (EudraCT Number)