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Cannabidiol for Treatment of Non-affective Psychosis and Cannabis Use

Primary Purpose

Dual Diagnosis

Status
Recruiting
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Cannabidiol
Risperidone
Sponsored by
Lone Baandrup
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dual Diagnosis focused on measuring psychosis, cannabis, clinical trial

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • ICD-10 diagnosis of schizophrenia (DF20.X), paranoid psychosis (DF22.X), acute/intermittent psychotic disorder (DF23.X), schizoaffective psychosis (DF25.X), other/not specified nonorganic psychotic disorder (DF28/DF29), or cannabis induced psychotic disorder (DF12.5)
  • PANSS ≥ 60 and score of ≥ 4 on ≥ 2 PANSS-Positive subscale items: Delusions (P1), conceptual disorganization (P2), hallucinatory behaviour (P3), grandiosity (P5), suspiciousness (P6)
  • Lifetime cannabis use
  • Age 18-45 years
  • Female patients of childbearing potential need to utilize a proper method of contraception

Exclusion criteria:

  • Treatment resistance as defined by treatment (ever) with clozapine
  • Dependence syndrome of alcohol or psychoactive substances other than cannabis (DF1X.2 other than DF12.2)
  • Psychotic disorder induced by alcohol or psychoactive substances other than cannabis (DF1X.5 other than DF12.5)
  • Treatment with a long-acting injectable antipsychotic within the past month (or corresponding to the usual interval between two injections)
  • Treatment with an oral antipsychotic within the past 7 days
  • Use of self-administered CBD products during the trial
  • Patients involuntarily admitted
  • Pregnancy or lactation
  • Severe physical illness that might influence the ability to comply with the protocol

Sites / Locations

  • Center for Neuropsychiatric Schizophrenia ResearchRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cannabidiol

Risperidone

Arm Description

Cannabidiol (Epidiolex®) (oral suspension)100 mg/ml dosed as 3 ml in the morning for 4 days, then increased to 3 ml in the morning and 3 ml in the evening, equivalent to CBD 300 mg BID, with a total treatment duration of 7 weeks. AND Risperione placebo, encapsulated tablet.

Risperidone (encapsulated tablet) dosed as 2 mg in the morning for 4 days, then increased with 2 mg in the morning and 2 mg in the evening, with a total treatment duration of 7 weeks AND Cannabidiol placebo, oral suspension

Outcomes

Primary Outcome Measures

Psychotic symptoms
Positive and Negative Syndrome Scale (PANSS) positive subscale, range 7-49. A measure of symptom severity. Higher values are worse.

Secondary Outcome Measures

Cannabis cessation (no use of cannabis within the past two weeks) (for current cannabis users at baseline)
Timeline follow back method
Cannabis use by self-reported days of cannabis use per week, since last study visit.
Timeline follow back method
Amount of cannabis use per day, self-reported, since last study visit.
PSYSCAN cannabis questionnaire# 6-8
Response
Response defined by PANSS total 25 percentile changes
Remission
Symptomatic remission is defined according to the Andreasen et al remission criteria. The criteria define symptomatic remission as a rating of no more than mild in four core positive and four core negative symptoms on the Positive and Negative Syndrome Scale (P1, P2 P3, N1, N4, N6, G5, G9,) that is sustained for ≥6 months. Because of the duration of this study, the requirement of 6 month will not be considered.
Global illness severity
Global illness severity is assessed with the Clinical Global Impression Scale (CGI). We will use the severity (CGI-S) at baseline and improvement (CGI-I) scores of the CGI at the following visits. Response will be defined as much improved or better on the CGI-I. The main item 'severity of illness' is measured on a 7-point Likert scale (from 1 'normal, not at all ill' to 7 'among the most extremely ill patients').
Psychosocial functioning
Personal and Social Performance Scale (PSP). Higher is better, range 1-100.
Neurocognitive functioning
Brief Assessment of Cognition in Schizophrenia (BACS). Neurocognitive Test Battery. One composite score and six subscales.
Subjective well-being
Subjective Well-being under Neuroleptics Scale (SWN). A measure of health-related quality of life.
Circadian rest-activity cycle
Actigraphy. A wrist-worne device that measures kinetic energy.
Subjective sleep quality
Pittsburgh Sleep Quality Index (PSQI). One total score, seven subscales.
Objective sleep evaluation
Polysomnography (PSG). A measure of objective sleep variables
Metabolomics
Markers for cannabinoids, dopamine and serotonin and their precursors and metabolites in the blood

Full Information

First Posted
September 22, 2019
Last Updated
July 28, 2023
Sponsor
Lone Baandrup
Collaborators
Danish Center for Sleep Medicine, Copenhagen University Hospital, Denmark, Glostrup University Hospital, Copenhagen, University of Copenhagen
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1. Study Identification

Unique Protocol Identification Number
NCT04105231
Brief Title
Cannabidiol for Treatment of Non-affective Psychosis and Cannabis Use
Official Title
Cannabidiol for Treatment of Non-affective Psychosis and Cannabis Use
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2021 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Lone Baandrup
Collaborators
Danish Center for Sleep Medicine, Copenhagen University Hospital, Denmark, Glostrup University Hospital, Copenhagen, University of Copenhagen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This trial examines the efficacy of cannabidiol (CBD) versus risperidone for treatment of psychosis in patients with non affective-psychosis and lifetime use of cannabis.
Detailed Description
People with psychosis and comorbid cannabis use are particularly difficult to treat because cannabis use worsens psychotic symptoms and increases the risk that a first-episode psychosis will progress to schizophrenia. It is the THC (tetrahydrocannabinol) content in cannabis that aggravates psychotic symptoms whereas the CBD content has potential therapeutic effects. This trial investigates treatment with CBD (without THC) versus risperidone (an antipsychotic agent) in people with psychosis and lifetime use of cannabis. We hypothesize that CBD will ameliorate psychotic symptoms and reduce the frequency of cannabis use to a larger extent than risperidone. Sleep disturbances are often a limiting factor in the treatment of psychosis, and it is also examined how CBD affects objective and subjective sleep quality as well as circadian rest-activity cycles. Based on previous studies investigating CBD as monotherapy in patients with schizophrenia, it is expected that CBD will be associated with fewer adverse events than risperidone.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dual Diagnosis
Keywords
psychosis, cannabis, clinical trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cannabidiol
Arm Type
Experimental
Arm Description
Cannabidiol (Epidiolex®) (oral suspension)100 mg/ml dosed as 3 ml in the morning for 4 days, then increased to 3 ml in the morning and 3 ml in the evening, equivalent to CBD 300 mg BID, with a total treatment duration of 7 weeks. AND Risperione placebo, encapsulated tablet.
Arm Title
Risperidone
Arm Type
Active Comparator
Arm Description
Risperidone (encapsulated tablet) dosed as 2 mg in the morning for 4 days, then increased with 2 mg in the morning and 2 mg in the evening, with a total treatment duration of 7 weeks AND Cannabidiol placebo, oral suspension
Intervention Type
Drug
Intervention Name(s)
Cannabidiol
Other Intervention Name(s)
Epidiolex
Intervention Description
Cannabidiol oral suspension
Intervention Type
Drug
Intervention Name(s)
Risperidone
Other Intervention Name(s)
Risperidon
Intervention Description
Risperidone, encapsulated tablet.
Primary Outcome Measure Information:
Title
Psychotic symptoms
Description
Positive and Negative Syndrome Scale (PANSS) positive subscale, range 7-49. A measure of symptom severity. Higher values are worse.
Time Frame
7 weeks follow-up
Secondary Outcome Measure Information:
Title
Cannabis cessation (no use of cannabis within the past two weeks) (for current cannabis users at baseline)
Description
Timeline follow back method
Time Frame
7 weeks follow-up
Title
Cannabis use by self-reported days of cannabis use per week, since last study visit.
Description
Timeline follow back method
Time Frame
7 weeks follow-up
Title
Amount of cannabis use per day, self-reported, since last study visit.
Description
PSYSCAN cannabis questionnaire# 6-8
Time Frame
7 weeks follow-up
Title
Response
Description
Response defined by PANSS total 25 percentile changes
Time Frame
7 weeks follow-up
Title
Remission
Description
Symptomatic remission is defined according to the Andreasen et al remission criteria. The criteria define symptomatic remission as a rating of no more than mild in four core positive and four core negative symptoms on the Positive and Negative Syndrome Scale (P1, P2 P3, N1, N4, N6, G5, G9,) that is sustained for ≥6 months. Because of the duration of this study, the requirement of 6 month will not be considered.
Time Frame
7 weeks follow-up
Title
Global illness severity
Description
Global illness severity is assessed with the Clinical Global Impression Scale (CGI). We will use the severity (CGI-S) at baseline and improvement (CGI-I) scores of the CGI at the following visits. Response will be defined as much improved or better on the CGI-I. The main item 'severity of illness' is measured on a 7-point Likert scale (from 1 'normal, not at all ill' to 7 'among the most extremely ill patients').
Time Frame
7 weeks follow-up
Title
Psychosocial functioning
Description
Personal and Social Performance Scale (PSP). Higher is better, range 1-100.
Time Frame
7 weeks follow-up
Title
Neurocognitive functioning
Description
Brief Assessment of Cognition in Schizophrenia (BACS). Neurocognitive Test Battery. One composite score and six subscales.
Time Frame
7 weeks follow-up
Title
Subjective well-being
Description
Subjective Well-being under Neuroleptics Scale (SWN). A measure of health-related quality of life.
Time Frame
7 weeks follow-up
Title
Circadian rest-activity cycle
Description
Actigraphy. A wrist-worne device that measures kinetic energy.
Time Frame
7 weeks follow-up
Title
Subjective sleep quality
Description
Pittsburgh Sleep Quality Index (PSQI). One total score, seven subscales.
Time Frame
7 weeks follow-up
Title
Objective sleep evaluation
Description
Polysomnography (PSG). A measure of objective sleep variables
Time Frame
7 weeks follow-up
Title
Metabolomics
Description
Markers for cannabinoids, dopamine and serotonin and their precursors and metabolites in the blood
Time Frame
7 weeks follow-up
Other Pre-specified Outcome Measures:
Title
Adverse events (AEs), discontinuation due to AEs, and serious adverse events (SAEs)
Description
Self-report
Time Frame
From baseline to 2 weeks after end of treatment
Title
Extrapyramidal and other side effects
Description
Udvalget for Kliniske Undersoegelser (UKU) short version A clinician-rated scale to assess antipsychotic side effects
Time Frame
7 weeks follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: ICD-10 diagnosis of schizophrenia (DF20.X), paranoid psychosis (DF22.X), acute/intermittent psychotic disorder (DF23.X), schizoaffective psychosis (DF25.X), other/not specified nonorganic psychotic disorder (DF28/DF29), or cannabis induced psychotic disorder (DF12.5) PANSS ≥ 60 and score of ≥ 4 on ≥ 2 PANSS-Positive subscale items: Delusions (P1), conceptual disorganization (P2), hallucinatory behaviour (P3), grandiosity (P5), suspiciousness (P6) Lifetime cannabis use Age 18-45 years Female patients of childbearing potential need to utilize a proper method of contraception Exclusion criteria: Treatment resistance as defined by treatment (ever) with clozapine Dependence syndrome of alcohol or psychoactive substances other than cannabis (DF1X.2 other than DF12.2) Psychotic disorder induced by alcohol or psychoactive substances other than cannabis (DF1X.5 other than DF12.5) Treatment with a long-acting injectable antipsychotic within the past month (or corresponding to the usual interval between two injections) Treatment with an oral antipsychotic within the past 7 days Use of self-administered CBD products during the trial Patients involuntarily admitted Pregnancy or lactation Severe physical illness that might influence the ability to comply with the protocol
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lone Baandrup, MD, PhD
Phone
30270879
Ext
0045
Email
lone.baandrup@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lone Baandrup, MD, PhD
Organizational Affiliation
Mental Health Services Capital Region in Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Neuropsychiatric Schizophrenia Research
City
Glostrup
ZIP/Postal Code
2600
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jesper Ø Rasmussen, MD
Phone
21576336
Ext
0045
Email
jesper.oestrup.rasmussen@regionh.dk
First Name & Middle Initial & Last Name & Degree
Lone Baandrup, Med.Sc.D
Phone
91165903
Ext
0045
Email
lone.baandrup@regionh.dk

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data will be available. In addition, the study protocol will be available. Data will be available after publication of planned primary and secondary analyses. There will be no end date for availability of data. Individual participant data will be available for meta-analysis. Proposals should be directed to: lone.baandrup@regionh.dk. To gain access, data requestors will need to sign a data access agreement.
IPD Sharing Time Frame
Data will be available after publication of planned primary and secondary analyses. No end date.
IPD Sharing Access Criteria
Proposals should be directed to: lone.baandrup@regionh.dk. To gain access, data requestors will need to sign a data access agreement.
Citations:
PubMed Identifier
34391393
Citation
Rasmussen JO, Jennum P, Linnet K, Glenthoj BY, Baandrup L. Cannabidiol versus risperidone for treatment of recent-onset psychosis with comorbid cannabis use: study protocol for a randomized controlled clinical trial. BMC Psychiatry. 2021 Aug 14;21(1):404. doi: 10.1186/s12888-021-03395-9.
Results Reference
derived

Learn more about this trial

Cannabidiol for Treatment of Non-affective Psychosis and Cannabis Use

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