SchizophreniaCANGLIANCT02932605
Endocannabinoid Control of Microglia Activation as a New Therapeutic Target in the Treatment of Schizophrenia
A study testing Cannabidiol in people with Schizophrenia, run by UMC Utrecht at 1 site in Netherlands.
Trial summary
The main 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. Read more about this study
- Who is it for?
- Ages 16 to 40 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Cannabidiol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteNetherlands
- Study dates
- 3 Nov 2017to 31 Jan 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
The main 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.
Read the detailed description
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.
In this project, we propose to study endocannabinoid control of microglia activation as a new therapeutic target in the treatment of schizophrenia. Using a placebo-controlled, randomised, double-blind design, we will investigate this in a group of 36 recent-onset schizophrenia patients after four weeks of daily CBD treatment, in addition to their regular antipsychotic medication. First, we will examine if CBD treatment attenuates microglia activation and levels of peripheral inflammatory markers. In vivo microglia activation is assessed before and after treatment using 1H-MRS, with the level of myo-inositol being regarded as a marker of glia function. Second, we will determine if reduced microglia activation and levels of inflammatory markers relate to improvement of symptomatology and cognitive function. Third, we will assess how microglia activation and levels of inflammatory markers before treatment predict the clinical response to CBD.
- Conditions
- Schizophrenia
- Being tested
- Placebo, Cannabidiol
- Keywords
- Schizophrenia, Cannabidiol, Magnetic Resonance Spectroscopy (1H-MRS), Microglia
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo
CannabidiolDrug
Cannabidiol
| Study group | Role | What they receive |
|---|---|---|
| Cannabidiol | Experimental | Patients will be treated with 600mg CBD daily for 4 weeks (28 days) Receives: Drug: Cannabidiol |
| Placebo | Placebo comparator | Patients will be treated with placebo daily for 4 weeks (28 days) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
the concentration of prefrontal metabolites as measured with 1H-MRS
the concentration of prefrontal metabolites as measured with 1H-MRS, with the level of myo-inositol being regarded as a marker of glia function
Measured: 4 weeks
Secondary outcomes (14)
Tolerability associated with CBD treatment
Number of treatment-related adverse events as assessed by the study physician
Measured: 4 weeks
Psychotic symptoms
Measured with the Positive and Negative Syndrome Scale (PANSS)
Measured: 4 weeks
Depressive symptoms
Measured with the Hamilton Depression Rating Scale (HAM-D)
Measured: 4 weeks
Anxiety
Measured with the State-Trait Anxiety Inventory (STAI)
Measured: 4 weeks
Clinical impression
Measured with the Clinical Global Impressions Scale (CGI)
Measured: 4 weeks
Psychosocial functioning
Measured with the Global Assessment of Functioning scale (GAF)
Measured: 4 weeks
Social and Occupational functioning
Measured with the Social and Occupational Functional Assessment Scale (SOFAS)
Measured: 4 weeks
Role functioning
Measured with the Global Functioning Role (GF:R) scale
Measured: 4 weeks
Social functioning
Measured with the Global Functioning Social (GF:S) scale
Measured: 4 weeks
Cognitive function
Measured with the Brief Assessment of Cognition in Schizophrenia (BACS)
Measured: 4 weeks
CBD plasma concentrations
Measured: 4 weeks
Blood cytokine concentrations
Examples of cytokines that could be assessed in the current study include but are not restricted to interferon-γ, interleukin (IL)-1α, IL-1RA, IL-6, IL-10, IL-12, IL-15, tumour necrosis factor-α, and S100B
Measured: 4 weeks
Haematological blood parameters
Platelet activation and platelet aggregate formation are measured
Measured: 4 weeks
MRI measures
Brain structure and function
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2016 (estimated)
- Study start3 Nov 2017
- Primary completion31 Jan 2020
- Study completion31 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, M.G. Bossong, UMC Utrecht
- Investigators
- Matthijs Bossong, PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02932605
- Sponsor's protocol ID
- ABR58805
- Other IDs
- 2016-003529-41, 2016
- Acronym
- CANGLIA
- Status last verified
- Mar 2020
- First submitted
- 21 Sep 2016
- Last updated
- 27 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endocannabinoid Control of Microglia Activation as a New Therapeutic Target in the Treatment of Schizophrenia
- ClinicalTrials.gov ID
- NCT02932605
- Acronym / sponsor ID
- CANGLIA / ABR58805
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Cannabidiol, Magnetic Resonance Spectroscopy (1H-MRS), Microglia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Study start
- 3 Nov 2017 (actual)
- Primary completion
- 31 Jan 2020 (actual)
- Study completion
- 31 Jan 2020 (actual)
- First posted
- 13 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main 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.
Detailed description
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.
In this project, we propose to study endocannabinoid control of microglia activation as a new therapeutic target in the treatment of schizophrenia. Using a placebo-controlled, randomised, double-blind design, we will investigate this in a group of 36 recent-onset schizophrenia patients after four weeks of daily CBD treatment, in addition to their regular antipsychotic medication. First, we will examine if CBD treatment attenuates microglia activation and levels of peripheral inflammatory markers. In vivo microglia activation is assessed before and after treatment using 1H-MRS, with the level of myo-inositol being regarded as a marker of glia function. Second, we will determine if reduced microglia activation and levels of inflammatory markers relate to improvement of symptomatology and cognitive function. Third, we will assess how microglia activation and levels of inflammatory markers before treatment predict the clinical response to CBD.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cannabidiol | Experimental | Drug: CannabidiolPatients will be treated with 600mg CBD daily for 4 weeks (28 days) |
| Placebo | Placebo comparator | Drug: PlaceboPatients will be treated with placebo daily for 4 weeks (28 days) |
Who may qualify
- Ages
- 16 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPlacebo | Drug | Placebo |
| CannabidiolCannabidiol | Drug | Cannabidiol |
Primary outcome
the concentration of prefrontal metabolites as measured with 1H-MRS
Time frame: 4 weeks
the concentration of prefrontal metabolites as measured with 1H-MRS, with the level of myo-inositol being regarded as a marker of glia function
14 secondary outcomes
Tolerability associated with CBD treatment
Time frame: 4 weeks
Psychotic symptoms
Time frame: 4 weeks
Depressive symptoms
Time frame: 4 weeks
Anxiety
Time frame: 4 weeks
Clinical impression
Time frame: 4 weeks
Psychosocial functioning
Time frame: 4 weeks
Social and Occupational functioning
Time frame: 4 weeks
Role functioning
Time frame: 4 weeks
Social functioning
Time frame: 4 weeks
Cognitive function
Time frame: 4 weeks
CBD plasma concentrations
Time frame: 4 weeks
Blood cytokine concentrations
Time frame: 4 weeks
Haematological blood parameters
Time frame: 4 weeks
MRI measures
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2020.
- Individual participant dataSharing planned: No
Related trials for Schizophrenia
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthijs Bossong, PhD principal investigator
UMC Utrecht
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cannabidiol in people with Schizophrenia, run by UMC Utrecht at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the concentration of prefrontal metabolites as measured with 1H-MRS (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2020.