We think methylation patterns and gene expression profiles predict treatment outcome (respons + ADRs) after initiating CLZ.
ID
Source
Brief title
Health condition
Schizophrenia,schizophreniform and schizoaffective disorder Clozapine, psychotic disorders
Sponsors and support
Intervention
Outcome measures
Primary outcome
Reponse and the development of ADRs after clozapine intake. We think this is influenced by methylation patterns and gene expression
Secondary outcome
We measure non-genetic factors such as smoking, cannabis use, duration of illness etc., because we think these influence treatment outcome (ADRs+response) as well. In addition, we use the data with our other protocol (NTR 5257) to create a prediction model for clozapine response and side effects.
Background summary
Clozapine (CLZ) is one of the most effective antipsychotic medications, but with life-threatening adverse drug reactions (ADRs), such as agranulocytosis, diabetic ketoacidosis and gastrointestinal hypomotility and insidious adverse reactions such as metabolic syndrome (MetS). For many patients with schizophrenia spectrum disorders (SCZ), CLZ is the last resort because other antipsychotics have not resulted in sufficient clinical improvements. Prescribing CLZ in clinical practice therefore requires balancing ADR risk profile likelihoods with clinical response probabilities. This need highly contrasts with the current state of knowledge as it is unknown who will respond to CLZ and to what degree a specific patient may develop ADRs. Based on preclinical studies, we hypothesize that epigenetic and gene expression mechanisms influence treatment outcome (response + development ADRs) of CLZ. We will therefore investigate methylation patterns and gene expression profiles before and after initiation of CLZ pharmacotherapy. Furthermore, we will try and identify other predictive factors for treatment outcome following CLZ pharmacotherapy initiation.
In addition, we use the data with our other protocol (NTR 5248) to create a prediction model for clozapine response and side effects.
Study objective
We think methylation patterns and gene expression profiles predict treatment outcome (respons + ADRs) after initiating CLZ.
Study design
Patients have 3 visits: one before clozapine initiation, 4-12 weeks and 28 weeks after steady state.
Intervention
None
Marte van der Horst
Heidelberglaan 100
Utrecht 3508 GA
The Netherlands
0887551460
mzvanderhorst@gmail.com
Marte van der Horst
Heidelberglaan 100
Utrecht 3508 GA
The Netherlands
0887551460
mzvanderhorst@gmail.com
Inclusion criteria
-he/she is about to initiate CLZ (i.e. he/she has an indication to start CLZ treatment according to the treating physician and he/she is willing to start on CLZ)
-he/she has received a diagnosis of schizophrenia, schizophreniform disorder, schizoaffective disorder or psychosis not otherwise specified.
-his/her age must be ≥18 years old
-he/she must be able to speak and read the Dutch language
-he/she must be mentally competent with regard to a decision to participate in the current study
Exclusion criteria
- admission to a psychiatric unit involuntarily in the context of an ‘inbewaringstelling’ (IBS)
- a history of Parkinson’s disease
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL5125 |
| NTR-old | NTR5257 |
| CCMO | NL52728.041.15 |
| OMON | NL-OMON50475 |