Our projects

OUR PROJECTS

CLOZIN

CLOZIN is a combined cohort and prospective study, including in the Netherlands, Germany and Finland. We include patients that use, used or will use clozapine and take blood for DNA and methylation pattern analysis and we perform a small clinical evaluation. The goals are:

1. To assess whether the genetic architecture of this severe SCZ phenotype differs from the broad DSM-based SCZ phenotype.

2. To predict clozapine response and side effects based on phenotypic and genetic data obtained in this study.

The background behind the first goal is that previous genetic studies find so many associations that it is unclear what is really relevant, it is hard to find causal relationships and the explained variance is low. In CLOZIN, the illness of the patients we include is more enduring and more severe, which can solve these problems. The background behind the second goal is to answer a clinically relevant question. Clozapine is very effective, but there is a risk for lethal side effects such as agranulocytosis, but also for side effects that are more common and frustrating for patients, such as weight gain. If we know beforehand that the response of patients will be good, without development of these side effects (or at least knowing there will be some weight gain), this will help clinicians to prescribe clozapine earlier in treatment. It is also likely that patients stay longer on clozapine as they know beforehand what side effects will develop and they will not stop because they are surprised by the side effects.

The study is still including patient and we are open for contacts with new sites, so if you are interested, please contact clozin@umcutrecht.nl!

More information about the study can be found on www.clozinstudy.com.

Enlighten Early

Enlighten early studies ALKS 3831, an investigational antipsychotic drug candidate designed by Alkermes to prevent or limit weight gain associated with olanzapine use. ALKS 3831 combines samidorphan, a new molecular entity, with olanzapine, in a single tablet. The Enlighten Early program is developed in order to compare weight gain in young adult patients with schizophrenia, schizophreniform or bipolar I disorder who are early in their illness and using olanzapine, to patients using ALKS 3831. The study is partly managed by the Clinical Trial Center, in close collaboration with Alkermes, Premier Research and the Vanguard Group (US).

Link to study: https://clinicaltrials.gov/ct2/show/NCT03187769?term=alks+3831&recrs=ab&rank=2

EULAST

Rationale: Schizophrenia is a chronic psychiatric illness with periods of remission and relapse. Patients vary in the frequency and severity of relapse, time until relapse and time in remission. Discontinuation of antipsychotic medication is by far the most important reason for relapse. A possible method to optimize medication adherence is to treat patients with long-term, depot medication rather than oral medication. However, despite its apparent “common sense” this approach has neither been universally accepted by practicing psychiatrists nor unequivocally demonstrated in clinical trials. Therefore, in this study we aim to investigate possible advantages of depot medication over oral antipsychotics in an independently designed and conducted, randomized, pragmatic trial.

Objective: The primary objective is to compare all cause discontinuation rates in patients with schizophrenia randomized to either one of the two depot medications (aripiprazole depot or paliperidone palmitate) with patients randomized to either one of the two oral formulations of the same medication (aripiprazole or paliperidone) over an 18 month follow-up period. Secondary objectives include differences in symptom severity, global functioning, quality of life, psychosocial functioning, side-effects, safety measures, as well as associations between immune parameters and these outcome measures. In addition, the a-priori opinion of the patients and investigators regarding the comparative values of oral vs. depot medication is assessed.

Design and population: EULAST is a pragmatic, randomized, open label, multicenter, multinational comparative trial. Patients aged 18 years or older, having experienced the first psychosis 6 months to 7 years ago (time of first psychosis is defined as the first contact with a health care professional in relation to psychotic symptoms), currently meeting DSM-IV-R criteria for schizophrenia with an indication (patient or physician initiated) to receive medication or to switch to another antipsychotic drug.
Intervention: Randomization and medication switch (1:1:1:1) to either paliperidone palmitate or aripiprazole depot or oral aripiprazole or oral paliperidone.

Main study parameters: Primary outcome is all cause discontinuation (i.e. discontinuation or switching of medication, adding a second antipsychotic agent beyond the allowed limit, patient withdraws consent, patient has missed a monthly visit despite a reminder). Secondary outcome measures includes scores on the Positive and Negative Symptom Scale (PANSS), CGI, Personal and Social Performance scale (PSP), Subjective Wellbeing (SWN), quality of life (EQ-5D), cognitive functioning, resource utilization, immune parameters and safety measures.

Link to the website: https://www.eulast.eu/

OPTIMISE

Although many antipsychotics are available for the treatment of psychosis, currently it is unknown which antipsychotic should be initiated first, how long treating physicians should wait before switching to another antipsychotic, and which antipsychotic to select in that case. This large scale European study aims to improve current treatment of schizophrenia by testing a treatment algorithm, including amisulpride, olanzapine and clozapine, for patients with a first episode of psychosis. To achieve this, a consortium of 18 psychiatric institutes based in Europa and Israel has been formed from which almost 500 patients with first episode psychosis and a diagnosis of schizophrenia or schizophreniform disorder were enrolled. Neuroimaging data is collected on a subsample (n=200), including MRI, fMRI and spectroscopy. Various blood parameters, including proteomic, metabolomics, genetics and immune parameters are also investigated. All patients who participated in the treatment algorithm study component were welcome to continue into a Psychosocial Intervention component, where an active intervention program was compared to treatment as usual in order to study the effect on treatment adherence.

Link to study website: www.optimisetrial.eu

PRISM

It is difficult to diagnose psychiatric and neurological diseases. Symptoms of one disorder are often similar to symptoms of other disorders, which makes correct diagnosis difficult. A symptom that occurs in different psychiatric and neurological disorders is ‘social withdrawal’. This means that someone spends less time with other people than he or she used to do. Social withdrawal is seen in Alzheimer’s disease for example, but also in patients suffering from schizophrenia. In this study we aim to investigate the biological underpinnings of social withdrawal. We also measure the cognitive abilities of participants. Through this study, we expect to improve the understanding of symptoms in schizophrenia and Alzheimer’s disease. This might facilitate accurate diagnosis and treatment. We’ve chosen two disorders that differ from each other in many areas, but are similar with respect to social withdrawal. The PRISM study is a European research project conducted by a team of 23 partners from 8 European countries. The clinical study is carried out in two hospitals in Spain and three in the Netherlands. 

For more information visit our website: https://prism-project.eu/en/prism-study/

PSYSCAN

PSYSCAN is a large international multi-center study, funded by the 7th Framework Programme of the European Committee. The goal of PSYSCAN is to develop a method to predict illness onset, course and outcome for people with psychosis. This is done by combining imaging methods, biological sampling, cognitive and demographic data from patients who experienced a first episode of psychosis. PSYSCAN takes place in nine European countries, Israel and Australia, and we hope to include 465 patients with a first episode of psychosis by November 2018.

The study website: www.psyscan.eu

PURPOSE

PURPOSE is an international, multicentre, randomised, double-blind, placebo-controlled clinical trial. The study aims to recruit 220 individuals between 13 and 20 years old who are at an ultra-high risk (UHR) for developing psychosis. Participants are recruited by 16 centres across 9 countries. UHR subjects are treated daily with either omega-3 fatty acids or placebo for six months, followed by a 1.5-year clinical follow-up. A limited number of participating centres will additionally recruit a sample of 110 healthy controls without an intervention.

Primary objective of this randomised controlled trial is to compare transition rates to psychosis between individuals who are at UHR for developing psychosis and randomised to treatment with omega-3 fatty acids to those randomised to placebo. Additional objectives include a comparison between the two treatment arms regarding other study parameters such as symptomatology, blood levels of immune parameters, and brain structure and function as measured with MRI, and both cross-sectional and longitudinal comparisons of study parameters between UHR subjects and healthy controls.

The study website: www.purposetrial.eu

AIMS-2

AIMS-2-CT1 is an international, multicenter, randomized, double-blind, placebo-controlled trial in children and adolescents (5-17) with Autism Spectrum Disorders focusing on the GABA/glutamate equilibrium, with a repurposed compound: Arbaclofen. The aim is to assess the efficacy, safety, and tolerability of Arbaclofen, a drug that targets core and/or comorbid symptoms of ASD, in children and adolescents with Autism Spectrum Disorders. The study will continue until 130 participants are enrolled. Patients will be recruited at 7 sites in Europe.

The primary objective of this RCT is to examine the effect of Arbaclofen vs. placebo on social function. Additional objectives include an examination of the effect of Arbaclofen vs. placebo on measures of global function and on safety and tolerability of Arbaclofen in children and adolescents with ASD. Other secondary objectives focus on exploring the effect of Arbaclofen vs. placebo on other adaptive domains, on measures of social abilities and social responsiveness, on other measures of core symptoms, on associated psychopathological symptoms and on whether measures of electrophysiology (EEG) and sensory discrimination are associated with either response to treatment.

 The study website: https://www.aims-2-trials.eu/