Ignite Creation Date:
2025-12-25 @ 3:32 AM
Ignite Modification Date:
2026-02-23 @ 1:53 PM
Study NCT ID:
NCT02932605
Status:
COMPLETED
Last Update Posted:
2020-03-27
First Post:
2016-09-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Endocannabinoid Control of Microglia Activation as a New Therapeutic Target in the Treatment of Schizophrenia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D012559', 'term': 'Schizophrenia'}], 'ancestors': [{'id': 'D019967', 'term': 'Schizophrenia Spectrum and Other Psychotic Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D002185', 'term': 'Cannabidiol'}], 'ancestors': [{'id': 'D002186', 'term': 'Cannabinoids'}, {'id': 'D013729', 'term': 'Terpenes'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 32}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-11-03', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-03', 'completionDateStruct': {'date': '2020-01-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-03-26', 'studyFirstSubmitDate': '2016-09-21', 'studyFirstSubmitQcDate': '2016-10-10', 'lastUpdatePostDateStruct': {'date': '2020-03-27', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2016-10-13', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2020-01-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'the concentration of prefrontal metabolites as measured with 1H-MRS', 'timeFrame': '4 weeks', 'description': 'the concentration of prefrontal metabolites as measured with 1H-MRS, with the level of myo-inositol being regarded as a marker of glia function'}], 'secondaryOutcomes': [{'measure': 'Tolerability associated with CBD treatment', 'timeFrame': '4 weeks', 'description': 'Number of treatment-related adverse events as assessed by the study physician'}, {'measure': 'Psychotic symptoms', 'timeFrame': '4 weeks', 'description': 'Measured with the Positive and Negative Syndrome Scale (PANSS)'}, {'measure': 'Depressive symptoms', 'timeFrame': '4 weeks', 'description': 'Measured with the Hamilton Depression Rating Scale (HAM-D)'}, {'measure': 'Anxiety', 'timeFrame': '4 weeks', 'description': 'Measured with the State-Trait Anxiety Inventory (STAI)'}, {'measure': 'Clinical impression', 'timeFrame': '4 weeks', 'description': 'Measured with the Clinical Global Impressions Scale (CGI)'}, {'measure': 'Psychosocial functioning', 'timeFrame': '4 weeks', 'description': 'Measured with the Global Assessment of Functioning scale (GAF)'}, {'measure': 'Social and Occupational functioning', 'timeFrame': '4 weeks', 'description': 'Measured with the Social and Occupational Functional Assessment Scale (SOFAS)'}, {'measure': 'Role functioning', 'timeFrame': '4 weeks', 'description': 'Measured with the Global Functioning Role (GF:R) scale'}, {'measure': 'Social functioning', 'timeFrame': '4 weeks', 'description': 'Measured with the Global Functioning Social (GF:S) scale'}, {'measure': 'Cognitive function', 'timeFrame': '4 weeks', 'description': 'Measured with the Brief Assessment of Cognition in Schizophrenia (BACS)'}, {'measure': 'CBD plasma concentrations', 'timeFrame': '4 weeks'}, {'measure': 'Blood cytokine concentrations', 'timeFrame': '4 weeks', 'description': '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'}, {'measure': 'Haematological blood parameters', 'timeFrame': '4 weeks', 'description': 'Platelet activation and platelet aggregate formation are measured'}, {'measure': 'MRI measures', 'timeFrame': '4 weeks', 'description': 'Brain structure and function'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Schizophrenia', 'Cannabidiol', 'Magnetic Resonance Spectroscopy (1H-MRS)', 'Microglia'], 'conditions': ['Schizophrenia']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nIn 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '40 Years', 'minimumAge': '16 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* 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.\n* Age 16 - 40\n* Onset of first psychosis no longer than five years ago\n* Written informed consent of the subject\n\nExclusion Criteria:\n\n* Any clinically significant medical condition that may influence the results of the trial or affect the ability to take part in a trial\n* Routine laboratory screening values considered an impediment for participation by a medical doctor (see Appendix 1)\n* Positive urine test on any drug of abuse, except cannabis\n* 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\n* Use of glucocorticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs) within two weeks prior to study inclusion\n* 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)\n* Intake of investigational drug within one month prior to study inclusion\n* Daily use of alcohol or drugs of abuse (including cannabis) in the three months prior to study inclusion\n* Any current or previous neurological disorder, including epilepsy\n* History of head injury resulting in unconsciousness lasting at least 1 hour\n* IQ \\< 70, as measured with Dutch version of the National Adult Reading Test (DART)\n* Breastfeeding, pregnancy or attempting to conceive\n* MRI contraindications, e.g. claustrophobia or metal objects in or around the body'}, 'identificationModule': {'nctId': 'NCT02932605', 'acronym': 'CANGLIA', 'briefTitle': 'Endocannabinoid Control of Microglia Activation as a New Therapeutic Target in the Treatment of Schizophrenia', 'organization': {'class': 'OTHER', 'fullName': 'UMC Utrecht'}, 'officialTitle': 'Endocannabinoid Control of Microglia Activation as a New Therapeutic Target in the Treatment of Schizophrenia', 'orgStudyIdInfo': {'id': 'ABR58805'}, 'secondaryIdInfos': [{'id': '2016-003529-41', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Cannabidiol', 'description': 'Patients will be treated with 600mg CBD daily for 4 weeks (28 days)', 'interventionNames': ['Drug: Cannabidiol']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Patients will be treated with placebo daily for 4 weeks (28 days)', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo', 'armGroupLabels': ['Placebo']}, {'name': 'Cannabidiol', 'type': 'DRUG', 'description': 'Cannabidiol', 'armGroupLabels': ['Cannabidiol']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Utrecht', 'country': 'Netherlands', 'facility': 'University Medical Center Utrecht', 'geoPoint': {'lat': 52.09083, 'lon': 5.12222}}], 'overallOfficials': [{'name': 'Matthijs Bossong, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'UMC Utrecht'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'UMC Utrecht', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor', 'investigatorFullName': 'M.G. Bossong', 'investigatorAffiliation': 'UMC Utrecht'}}}}