The aim of the proposed study is to investigate the effects of antipsychotic medication on total brain volume and specific brain structures known to be affected in schizophrenia, such as hippocampus, thalamus, caudate, parietal and prefrontal cortex…
ID
Source
Brief title
Condition
- Schizophrenia and other psychotic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter concerns brain volume measured with anatomical
magnetic resonance imaging (MRI), at two time points: at baseline and at 12
months follow-up. MRI scans will be acquired on a standard 3 Tesla Siemens
clinical scanner located at the Radiology Department of the University Medical
Center Groningen.
Secondary outcome
A secundary study parameter is retinal nerve fiber layer (RNFL) thickness, as
measured by optical coherence tomography (OCT). The measurement takes 10
minutes and is non-invasive. Results will be correlated to whole brain volume
and total grey volume assessed with MRI. The RNFL of FEP patients will be
compared with the RNFL of healthy controls.
Other secundary study parameters are assessed during and as part of the HAMLETT
core study and include: Physical health, movement disorders, language, symptom
severity, cognition, global functioning, social functioning, medication use and
adverse events.
Background summary
Previous research has reported a negative association between cumulative dose
of antipsychotic medication and brain volume in patients with schizophrenia. A
problem with these studies is that patients with severe symptoms tend to need a
higher dose than patients with mild symptoms, i.e. it is impossible to
disentangle whether smaller brain volumes are caused by more medication use or
higher symptom severity.
Study objective
The aim of the proposed study is to investigate the effects of antipsychotic
medication on total brain volume and specific brain structures known to be
affected in schizophrenia, such as hippocampus, thalamus, caudate, parietal and
prefrontal cortex, as measured with magnetic resonance imaging (MRI).
We will also investigate effects of sex and type of antipsychotic medication on
brain volumes. Furthermore, we will associate brain volume loss between the two
scans (12 months follow-up) with short and long-term clinical outcome of the
patients, as assessed by the HAMLETT core study and we will associate retinal
nerve fiber layer (RNFL) thickness, as measured by optical coherence tomography
(OCT) with brain volume as measured by MRI. RNFL will be compared between FEP
patients and healthy controls.
Study design
The HAMLETT study is a large Dutch clinical trial that randomizes patients
after remission of a first psychotic episode, to continue or reduce/discontinue
their antipsychotic medication. It is performed in the UMC Utrecht and UMC
Groningen (Handling Antipsychotic Medication: Long-term Evaluation of Targeted
Treatment; Protocol number: [62202.042.17]/80-84800-98-41015) and funded by the
Dutch research organization (ZonMW; grant number 8480411003). The study is
currently including 512 participants over the course of three years. The
current add-on study aims to add MRI measurements for participants of the
HAMLETT study at baseline and at a 12 months follow-up, using an observational
design.
Study burden and risks
Subjects of this study will undergo two MRI scans. Each MRI scan will last 45
minutes and will pose minimal risk. Participants will be exposed to a
field-strength of 3 Tesla and scanner noise. Thus far, there is no evidence to
suggest that exposing humans to a magnetic field of this strength has a
negative influence on their health. With regard to the noise, earplugs and
headphones will be provided. The small space of the MRI scanner may cause
anxiety to those with claustrophobia. The potential benefit to society in the
future is considerable if the findings lead to more insight in effects of
antipsychotic medication on brain volume. There is no individual benefit to the
participants.
Healthy controls undergo a single OCT scan, which is noninvasive, lasts for
only 10 minutes, and poses minimal risk.
Antonius Deusinglaan 2
Groningen 9713 AW
NL
Antonius Deusinglaan 2
Groningen 9713 AW
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria for FEP patients:
1. The participant has had a first episode of psychosis and uses antipsychotic
medication.
2. Psychotic symptoms are in remission for 3-6 months with an antipsychotic.
3. Age 18-60 years.
4. The participant understands the study and is able to provide written
informed consent.
5. HAMLETT is the only medical-scientific medication study in which the patient
participates.
6. Sufficient command of the Dutch language.
Inclusion criteria for healthy controls for OCT:
1. Age 18-60 years.
2. The participant understands the study and is able to provide written
informed consent.
Exclusion criteria
Exclusion criteria for FEP patients:
1. Dangerous or harmful behaviour occurred during the psychosis
2. Coercive treatment (based on judicial ruling)
3. The refusal to be informed of structural brain abnormalities that could be
detected during the experiment
4. MRI contra-indications, e.g. Ferrous objects in or around the body, or
claustrophobia
5. Pregnancy
Exclusion criteria for healthy controls for the OCT-scan:
1. (History of) diagnosed psychiatric disorders
2. (History of) psychotropic medication use
3. (History of) neurological diseases that may affect the brain
4. (History of) substance abuse
5. (History of) ophthalmological disorders, as determined with the
questionnaire on eye health ('Vragenlijst ooggezondheid*)
6. (History of) systemic and autoimmune diseases that may affect the eye or
optic nerve, e.g. diabetes, glaucoma or refractory arterial hypertension
7. First-degree family member with glaucoma
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL66377.042.18 |