1. To assess whether a. Neuromelanin-sensitive MRI (nMRI) is a suitable biomarker for TRb. Plasma DDC activity is a suitable biomarker for TR2. To increase our insight in the role of glutamate in the anterior cingulate cortex (ACC) in TR and assess…
ID
Source
Brief title
Condition
- Schizophrenia and other psychotic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Treatment resistance
- Neuromelanin contrast ratio on nMRI
- Glutamate/Creatine ratio on MRS in ACC
- Plasma DDC activity
- [18F]DOPA influx (Ki) value (for subgroup of 40 patients)
Secondary outcome
- Side effects of antipsychotics
- Symptom scores on PANSS
- Neuropsychological ratings
Background summary
Treatment resistance (TR) in schizophrenia is a major clinical problem with
20-35% of psychotic patients showing non-response to antipsychotic treatment.
This leads to months to years of delay in effective treatment, resulting in
hospitalization and unnecessary side effects of ineffective antipsychotics. We
need a biomarker that could be used to switch TR patients at an early stage to
clozapine, the only antipsychotic with recognized superior effectiveness in TR.
A well-established finding in schizophrenia, using [18F]F-DOPA positron
emission tomography (PET) imaging, is increased striatal dopamine synthesis,
but interestingly TR patients don*t show altered synthesis. PET imaging however
is too costly and invasive to use for TR screening. A novel
neuromelanin-sensitive MRI sequence (nMRI), which indirectly measures striatal
dopamine synthesis, has great potential as biomarker for TR. nMRI indeed shows
increased signal in schizophrenia patients, but has not yet been tested in TR.
Another potential biomarker is a recently developed plasma measure of dopa
decarboxylase (DDC) activity, an enzyme required for dopamine synthesis.
Furthermore, the role of other neurotransmitters than dopamine in TR is
underexposed, of which glutamate is a likely candidate.
Study objective
1. To assess whether
a. Neuromelanin-sensitive MRI (nMRI) is a suitable biomarker for TR
b. Plasma DDC activity is a suitable biomarker for TR
2. To increase our insight in the role of glutamate in the anterior cingulate
cortex (ACC) in TR and assess whether it is a potential biomarker for TR
Study design
Prospectief
Study burden and risks
Patients will be assessed on two separate occasions:
(1) Interview, MRI (eventual questionnaires, neuropsychological tasks, blood
draw)
(2) interview, MRI (eventual questionnaires, neuropsychological tasks and blood
draw) (6 months later).
A subgroup of 40 participants will have an additional visit at baseline for an
[18F]F-DOPA PET scan.
Risks: For the subgroup of 40 patients, the radiation dose for this study is
3.9 mSv and falls within category IIb (minor to intermediate) and is lower than
most diagnostic CT scans.
Healthy controls will be assessed on one occasion:
(1) Interview, MRI, questionnaires and neuropsychological tasks
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
For patients:
- First episode psychosis
- Age 18-35 years old;For healthy contols:
- Age 18-35 years old
Exclusion criteria
- Antipsychotic use longer than one year
- Dependence on other substances of abuse than nicotine or cannabis
- Use of amphetamine, cocaine or medication for ADHD (attention deficit hyperactivity disorder), since these drugs influence the dopamine system
- Neurological disorder (e.g. epilepsy) or evidence of brain damage
- Inability to provide informed consent;In addition to the exclusion criteria mentioned above, healthy control subjects are not allowed to have any kind of psychiatric disorder;Exclusion criteria directly related to MRI scanning:
- Contra-indications for MRI (including pacemaker, ferromagnetic implants, claustrophobia)
- Pregnancy;Exclusion criteria directly related to PET/CT scanning (for subgroup of 40 patients):
- Participation in a scientific examination where radiation was used, in the last year.
- Positive urine drug screen on the day of the PET/CT scan. Participants will be tested on cannabis, amphetamine, XTC, cocaine and opiates. Only recent cannabis use will be accepted.
- In women: positive pregnancy test on the day of the PET/CT scan and lactation.
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 | 7430 |
| CCMO | NL63410.018.17 |
| OMON | NL-OMON21525 |