To investigate whether methylation patterns/levels and gene expression profiles predict treatment outcome after initiating CLZ.
ID
Source
Brief title
Condition
- Schizophrenia and other psychotic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Response to CLZ is measured using the Positive and Negative Syndrome Scale
(PANSS) and the first two questions of the Clinical Global Impression (CGI).
The results will be linked to changes in targeted methylation and gene
expression. Furthermore, the presence of several Adverse Drug Reactions are
assessed.
Secondary outcome
Secondary:
1. To identify non-genetic predicting factors for treatment outcome after
initiation of CLZ.
2. To predict reponse and side effects
3. To assess whether the genetic architecture of this severe SCZ phenotype
differs from the broad DSM-based SCZ phenotype. *
4. To detect genetic associations within the current severe SCZ phenotype by
performing a case control comparison with healthy participants. *
5. To investigate whether CLZ use increases or decreases the risk of
cardiovascular disease and early death. *
* These goals are the main objectives in our other protocol entitled *Phenomics
and genomics of CLZ pharmacotherapy - current users*. To make optimal use of
patients* DNA and to increase power for that other study we will ask
participants in the current study for informed consent to use their DNA for
these objectives.
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 when 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 (here defined as response and
development of ADRs) after CLZ initiation. 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.
Since, patient on clozapine have their leukocytes checked regularly, we
can collect the blood for DNA analyses non-invasively and ask them questions
before the initiation (max. 10 days after initiation) of clozapine and 4-12 and
28 weeks after the initiation.
At last, because considerable debate exists as to whether clozapine use
increases or decreases risk of cardiovascular disease and early death, we would
like to ask patient for consent to follow them up on long term.
Study objective
To investigate whether methylation patterns/levels and gene expression profiles
predict treatment outcome after initiating CLZ.
Study design
This is a prospective study in which both phenotypic and (epi)genotypic data
are extracted from this study population starting on clozapine.
We will include 300 patients who are about to initiate clozapine treatment may
be included during the study duration of six years.
Study burden and risks
All patients starting with CLZ regularly have their blood drawn for routine
white blood cell counts and/or CLZ blood level assessments. No additional
risks will be attached to the study as the blood necessary for DNA extraction
for the current study will be drawn from these routinely performed
venipunctures. Time investment is three times about 1 hour and 20 minutes.
Universiteitsweg 100
Utrecht 3584 CG
NL
Universiteitsweg 100
Utrecht 3584 CG
NL
Listed location countries
Age
Inclusion criteria
-he/she is about to initiate clozapine
-he/she has received a diagnosis of schizophrenia, schizophreniform,
schizoaffective disorder or psychosis not otherwise specified
(DSM-IV)/(un)specified other schizospectrum psychotic disorder
-he/she must be able to speak and read the Dutch language
- he/she must be 18 years or older
-he/she must understand the information provided about the study and understand
the consequences of participating and express a willingness to participate.
This estimation is done by the treating physician during the informed consent
procedure.
Exclusion criteria
- admission to a psychiatric unit involuntarily in the context of an
*inbewaringstelling* (IBS)
- when the treating physician doubts if the patient understands the
information/consequences of participation or the willingness to participate
- Patients with Parkinson*s disease
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| Other | 5257 |
| CCMO | NL52728.041.15 |
| OMON | NL-OMON20290 |