The primary objective of this study is to compare microglia activation as measured with proton Magnetic Resonance Spectroscopy (1H-MRS) between recent-onset schizophrenia patients who are randomised to CBD and those randomised to placebo. Secondary…
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 is the concentration of prefrontal metabolites as
measured with 1H-MRS, with the level of myo-inositol being regarded as a marker
of glia function.
Secondary outcome
In addition, symptomatology will be examined using semi-structured interviews
and questionnaires including the Positive and Negative Syndrome Scale (PANSS),
Global Assessment of Functioning scale (GAF), Clinical Global Impression Scale
(CGI) and Hamilton Depression Rating Scale (HAM-D). Cognition will be assessed
using the Brief Assessment of Cognition in Schizophrenia (BACS), which is a
validated battery of neuropsychological tests that capture key deficits
associated with psychosis, such as attention, memory, verbal fluency and
executive function. Blood samples will be drawn to assess CBD plasma
concentrations and immune and haematological parameters. Finally, brain
structure and function are measured using MRI techniques.
Background summary
Schizophrenia is a chronic and severe mental disorder with an urgent need for
new and more effective treatments. A promising novel pharmacological target in
this respect is the endocannabinoid system. In particular the cannabinoid
compound cannabidiol (CBD) displays a highly favourable profile for development
as a new antipsychotic agent. Increasing evidence indicates a significant role
for neuroinflammation in the pathophysiology of schizophrenia, especially for
activation of resident macrophages of the brain: microglia. Interestingly,
converging preclinical evidence suggests that microglia activation is under
control of the endocannabinoid system. However, how manipulation of the
endocannabinoid system affects microglia activation in humans has not been
established, but it is presumably related to clinical improvement of
schizophrenia patients.
Study objective
The primary objective of this study is to compare microglia activation as
measured with proton Magnetic Resonance Spectroscopy (1H-MRS) between
recent-onset schizophrenia patients who are randomised to CBD and those
randomised to placebo. Secondary objectives include comparisons between the two
treatment arms regarding symptomatology, inflammatory and haematological blood
markers, cognitive function, and brain structure and function. Third, it will
be examined how microglia activation and inflammatory markers before treatment
predict the clinical response to CBD, and correlations between study parameters
are assessed.
Study design
A randomised, double-blind, placebo-controlled between-subjects intervention
study.
Intervention
Schizophrenia patients are randomised to daily treatment with either 600 mg CBD
or placebo for four weeks, in addition to their regular antipsychotic
medication.
Study burden and risks
This study includes three site visits. The first visit is the screening visit,
which consists of screening for in- and exclusion criteria. Blood will be drawn
for routine laboratory tests. At both visits 2 and 3, which is before and after
four weeks of daily CBD or placebo treatment, patients will undergo an MRI
session of at maximum sixty minutes, consisting of 1H-MRS, structural MRI, and
functional MRI at rest and during reward processing. Both visits include
examination of symptomatology, psychosocial and cognitive function, and drug
use. Venous blood samples are drawn to assess immune markers, haematological
parameters and CBD plasma concentrations. Both blood sampling and MRI are safe
procedures; standard procedures are followed, which will be performed by
appropriately trained staff to minimise risks. Participation in this study may
be of therapeutic benefit to patients since treatment with CBD has been
associated with both clinical and functional improvement. Previous studies have
shown the potential of CBD as an effective, safe and well-tolerated
antipsychotic compound.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
* A DSM-IV diagnosis of 295.x (schizophrenia, schizophreniform disorder or schizoaffective disorder) or 298.9 (psychosis NOS). Diagnosis must be confirmed in writing by the treating psychiatrist.
* Age 16 - 40
* Onset of first psychosis no longer than five years ago
* Written informed consent of the subject
Exclusion criteria
* Any clinically significant medical condition that may influence the results of the trial or affect the ability to take part in a trial
* Routine laboratory screening values considered an impediment for participation by a medical doctor (see Appendix 1)
* Positive urine test on any drug of abuse, except cannabis
* Treatment with more than one antipsychotic agent or with an unstable dose of one type of antipsychotic medication in the month prior to study inclusion
* Use of glucocorticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs) within two weeks prior to study inclusion
* Use of co-medication other than antipsychotics that has a clinically relevant interaction with the cytochrome P450 (CYP) 2C19 or CYP3A classes of liver enzymes within two weeks prior to study inclusion (because CBD may be an inhibitor of these classes of liver enzymes; see paragraph 6.3)
* Intake of investigational drug within one month prior to study inclusion
* Daily use of alcohol or drugs of abuse (including cannabis) in the three months prior to study inclusion
* Any current or previous neurological disorder, including epilepsy
* History of head injury resulting in unconsciousness lasting at least 1 hour
* IQ < 70, as measured with Dutch version of the National Adult Reading Test (DART)
* Breastfeeding, pregnancy or attempting to conceive
* MRI contraindications, e.g. claustrophobia or metal objects in or around the body
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2016-003529-41-NL |
| ClinicalTrials.gov | NCT02932605 |
| CCMO | NL58805.041.16 |