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Effects of Cannabidiol (CBD) Versus Placebo as an Adjunct to Treatment in Early Psychosis

Primary Purpose

Early Psychosis

Status
Unknown status
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Cannabidiol oral solution
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Early Psychosis

Eligibility Criteria

16 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • First episode psychosis (onset within the last 2 years) or attenuated psychosis syndrome (APS), stabilized with treatment for at least 8 weeks prior to initiating the trial consistent with the FDA-NIMH-MATRICS guidelines for clinical trial design for clinical enhancing drugs:
  • Clinically stable and in a nonacute phase of their illness for at least 2 months, First episode psychosis participants will have been maintained on current antipsychotic for at least 6 weeks, with no change in antipsychotic dose for the previous 4 weeks while APS participants will be on the same treatment regimen (psychosocial or pharmacologic) for 4 weeks,
  • Exhibit no more than moderate levels of positive symptoms (defined by ratings of ≤ 4) on PANSS items P1 (delusions), P2 (conceptual disorganization), P3 (hallucinatory behavior), P5 (grandiosity), P6 (suspiciousness), and G8 (unusual thought content),
  • No more than a minimal level of depressive symptoms as assessed by the Calgary Depression Scale for Schizophrenia (CDSS)
  • Acceptable diagnoses will include APS, Psychosis NOS, Schizophreniform, Schizophrenia, and Schizoaffective per the Structured Clinical Interview for DSM-V.

Exclusion Criteria:

  • Concomitant medical or neurological illness;
  • Significant head injury;
  • Current substance abuse or positive toxicology screen for drugs including THC and CBD as detected by urine and blood samples.
  • Impaired intellectual functioning IQ<80; however those with an IQ i the 75-79 range will be include if WRAT reading > 85 suggesting higher premorbid IQ.
  • High suicidal risk assessed by the The Columbia-Suicide Severity Rating Scale (C-SSRS)42
  • Pregnant women and those who do not agree to avoid becoming pregnant
  • Patients requiring treatment with Azelastine, Azelastine; Fluticasone, Dronabinol, Valproic Acid, or Divalproex Sodium

Sites / Locations

  • UC San DiegoRecruiting
  • University of California, San DiegoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cannabidiol Augmentation

Placebo Augmentation

Arm Description

The cannabidiol will be administered as an oral solution to be mixed in any fluid. The formulation is 100 mg/ml. It will be administered at 500 mg at bedtime X 1 week then 500 mg BID.

Placebo will appear identical to the cannabidiol solution

Outcomes

Primary Outcome Measures

Positive and Negative Symptoms of Psychosis
Psychotic symptoms will be assessed with The Positive and negative psychotic syndrome scale (PANSS). This scale provides a summary score of all positive symptoms and all negative symptoms in participants who are already diagnosed with a psychotic disorder. The total score ranges from 30 to 210 with a higher score representing more symptoms.
Neurocognition
A Global Cognition Score will be assessed with Measurement and Treatment Research in Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) in all subjects.The Global Cognitive Score is a composite of the Z scores across the different cognitive domains in the MCCB. The range of scores is -1 to +1. Positive scores represent better cognitive functioning.
Prodromal Symptoms
The Scale of Prodromal Symptoms (SOPS) is part of the Structured Interview for Prodromal Syndromes (SIPS) diagnostic interview. This scale will be used to assess subsyndromal psychotic symptoms in participants who are diagnosed as Clinical High Risk for Psychosis. Positive and Negative Symptoms will be assessed as summary scores of all positive or negative items The minimum score on the SOPS total is 0 and Maximum is 24. A higher score represents more symptoms.
General Symptoms
The Brief Psychiatric Rating Scale (BPRS) will be used as an assessment of overall symptom ratings with a total score in all subjects. The minimum score is 24 and maximum is 168. A higher score represents more symptoms.
Clinical Global Impression Scale (CGI-S)
The CGI-S will provide a global psychopathology score for all subjects. The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. A "1" is considered normal while a "7" is extremely ill.

Secondary Outcome Measures

Peripheral Biomarkers of Inflammation
Panel of chemokines and cytokines expressed as "Mean Concentration Value". The minimum and maximum value for each measure between 0 and 40,280. In general higher values represent greater immune activation. Cytokines: Interferon-gamma, Interleukin-1, Interleukin-6, Interleukin-10, Interleukin-12p70, Tumor Necrosis Factor- alpha, Chemokines: Eotaxin-1, Eotaxin-3, Fracktalkine, Interleukin-8, Interferon Gamma-Induced Protein-10, Monocyte Chemotactic Protein-1, Macrophage-Derived Chemokine, Macrophage Inflammatory Protein-1a, Macrophage Inflammatory Protein-1b, Thymus and Activation Regulated Chemokine, Other: Brain Derived Neurotropic Factor
Cortisol
AM Salivary Cortisol is normally in the range of 100-750 ng/dL. Higher levels are thought to represent a greater stress response.

Full Information

First Posted
April 24, 2020
Last Updated
June 4, 2021
Sponsor
University of California, San Diego
Collaborators
Center for Medicinal Cannabis Research
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1. Study Identification

Unique Protocol Identification Number
NCT04411225
Brief Title
Effects of Cannabidiol (CBD) Versus Placebo as an Adjunct to Treatment in Early Psychosis
Official Title
Effects of Cannabidiol (CBD) Versus Placebo as an Adjunct to Treatment in Early Psychosis: Understanding the Mechanism and Mediators of Action
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Unknown status
Study Start Date
July 1, 2021 (Anticipated)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
June 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego
Collaborators
Center for Medicinal Cannabis Research

4. Oversight

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

5. Study Description

Brief Summary
This is an outpatient, single center, between-group, double blind, placebo controlled design. Approximately 120 adolescents and adult patients will be randomized to either have their treatment augmented with Cannabidiol Oral Solution (CBD) or with a matching CBD placebo for 8 weeks. The study will examine CBD as an augmentation strategy in early psychosis. It is hypothesized that CBD will improve symptoms, neurocognition, markers of inflammation and eating behaviors. Importantly, moderators and mediators of the CBD effects will be explored.
Detailed Description
Participants will be randomly assigned in a 1:1 ratio to receive CBD or matching Placebo as an add-on to antipsychotic medication in an 8 week double blind trial. In this study, Cannabidiol Oral Solution (CBD) product will be used. This product is manufactured and supplied by GW Pharmaceuticals. The formulation is a 100 mg/mL solution. The CBD compound will be dosed at 1000mg/day administered in two divided doses. The dose of CBD was selected based on previous controlled trials that demonstrate the efficacy of CBD in patients with schizophrenia. The maximum duration of the study from screening to follow up of outcomes and adverse events will be approximately 8 weeks. Participants will receive either the CBD or placebo within this eight.weeks and will also complete pre-treatment, midpoint (week 4) and post-treatment testing (week 8).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Early Psychosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This is a between-group, double blind, placebo controlled design.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Randomization will be assigned by study statisticians.
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cannabidiol Augmentation
Arm Type
Experimental
Arm Description
The cannabidiol will be administered as an oral solution to be mixed in any fluid. The formulation is 100 mg/ml. It will be administered at 500 mg at bedtime X 1 week then 500 mg BID.
Arm Title
Placebo Augmentation
Arm Type
Placebo Comparator
Arm Description
Placebo will appear identical to the cannabidiol solution
Intervention Type
Drug
Intervention Name(s)
Cannabidiol oral solution
Other Intervention Name(s)
Placebo
Intervention Description
Both the active drug (cannabidiol) and placebo will be in oral solution.
Primary Outcome Measure Information:
Title
Positive and Negative Symptoms of Psychosis
Description
Psychotic symptoms will be assessed with The Positive and negative psychotic syndrome scale (PANSS). This scale provides a summary score of all positive symptoms and all negative symptoms in participants who are already diagnosed with a psychotic disorder. The total score ranges from 30 to 210 with a higher score representing more symptoms.
Time Frame
Week 7
Title
Neurocognition
Description
A Global Cognition Score will be assessed with Measurement and Treatment Research in Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) in all subjects.The Global Cognitive Score is a composite of the Z scores across the different cognitive domains in the MCCB. The range of scores is -1 to +1. Positive scores represent better cognitive functioning.
Time Frame
week 7
Title
Prodromal Symptoms
Description
The Scale of Prodromal Symptoms (SOPS) is part of the Structured Interview for Prodromal Syndromes (SIPS) diagnostic interview. This scale will be used to assess subsyndromal psychotic symptoms in participants who are diagnosed as Clinical High Risk for Psychosis. Positive and Negative Symptoms will be assessed as summary scores of all positive or negative items The minimum score on the SOPS total is 0 and Maximum is 24. A higher score represents more symptoms.
Time Frame
Week 7
Title
General Symptoms
Description
The Brief Psychiatric Rating Scale (BPRS) will be used as an assessment of overall symptom ratings with a total score in all subjects. The minimum score is 24 and maximum is 168. A higher score represents more symptoms.
Time Frame
week 7
Title
Clinical Global Impression Scale (CGI-S)
Description
The CGI-S will provide a global psychopathology score for all subjects. The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. A "1" is considered normal while a "7" is extremely ill.
Time Frame
Week 7
Secondary Outcome Measure Information:
Title
Peripheral Biomarkers of Inflammation
Description
Panel of chemokines and cytokines expressed as "Mean Concentration Value". The minimum and maximum value for each measure between 0 and 40,280. In general higher values represent greater immune activation. Cytokines: Interferon-gamma, Interleukin-1, Interleukin-6, Interleukin-10, Interleukin-12p70, Tumor Necrosis Factor- alpha, Chemokines: Eotaxin-1, Eotaxin-3, Fracktalkine, Interleukin-8, Interferon Gamma-Induced Protein-10, Monocyte Chemotactic Protein-1, Macrophage-Derived Chemokine, Macrophage Inflammatory Protein-1a, Macrophage Inflammatory Protein-1b, Thymus and Activation Regulated Chemokine, Other: Brain Derived Neurotropic Factor
Time Frame
week 7
Title
Cortisol
Description
AM Salivary Cortisol is normally in the range of 100-750 ng/dL. Higher levels are thought to represent a greater stress response.
Time Frame
7 weeks
Other Pre-specified Outcome Measures:
Title
Eating Behavior
Description
Three Factor Eating Questionnaire will be used to query about eating behavior in different categories using total score: cognitive dietary restraint, disinhibition, and susceptibility to hunger. Each score is converted to a scaled score from 0 to 100 with the higher score representing more restraint, more dishinibition and less hunger.
Time Frame
7 weeks
Title
Body Mass Index
Description
Height and weight will be used to calculate Body Mass Index, a ratio of height and weight. Normal BMI is considered 18.5 to 25.
Time Frame
7 weeks
Title
Cholesterol
Description
serum will be drawn to measure total cholesterol, low density and high density lipoproteins along with Triglycerides. All are measured in mg/dL. Normal values include Total Cholesterol <=199, Triglycerides 30 - 149, High Density Lipoprotein 40-59, Low Density Lipoprotein <=129.
Time Frame
Baseline and week 7
Title
Electrophysiology Mismatch Negativity
Description
Mismatch Negativity (MMN) measured in an event related potential paradigm. The value is expressed in micorvolts and represents the difference in response to standard versus mismatch stimuli measure at 100 milliseconds post stimuli. The mismatch negativity value varies between 0 and -6 microvolts with greater negative numbers representing greater mismatch negativity. The MMN is thought primarily to reflect the activity of sensory memory, with, at most, moderate influences of higher-level cognitive processes, such as attention.
Time Frame
Baseline and week 7
Title
Electrophysiology - Prepulse Inhibition
Description
Prepulse Inhibition of the human startle response. Prepulse Inhibition is expressed as a percentage from 0 to 100 with the higher value presenting greater inhibition.
Time Frame
Baseline and week 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: First episode psychosis (onset within the last 2 years) or attenuated psychosis syndrome (APS), stabilized with treatment for at least 8 weeks prior to initiating the trial consistent with the FDA-NIMH-MATRICS guidelines for clinical trial design for clinical enhancing drugs: Clinically stable and in a nonacute phase of their illness for at least 2 months, First episode psychosis participants will have been maintained on current antipsychotic for at least 6 weeks, with no change in antipsychotic dose for the previous 4 weeks while APS participants will be on the same treatment regimen (psychosocial or pharmacologic) for 4 weeks, Exhibit no more than moderate levels of positive symptoms (defined by ratings of ≤ 4) on PANSS items P1 (delusions), P2 (conceptual disorganization), P3 (hallucinatory behavior), P5 (grandiosity), P6 (suspiciousness), and G8 (unusual thought content), No more than a minimal level of depressive symptoms as assessed by the Calgary Depression Scale for Schizophrenia (CDSS) Acceptable diagnoses will include APS, Psychosis NOS, Schizophreniform, Schizophrenia, and Schizoaffective per the Structured Clinical Interview for DSM-V. Exclusion Criteria: Concomitant medical or neurological illness; Significant head injury; Current substance abuse or positive toxicology screen for drugs including THC and CBD as detected by urine and blood samples. Impaired intellectual functioning IQ<80; however those with an IQ i the 75-79 range will be include if WRAT reading > 85 suggesting higher premorbid IQ. High suicidal risk assessed by the The Columbia-Suicide Severity Rating Scale (C-SSRS)42 Pregnant women and those who do not agree to avoid becoming pregnant Patients requiring treatment with Azelastine, Azelastine; Fluticasone, Dronabinol, Valproic Acid, or Divalproex Sodium
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kristin Cadenhead
Phone
619-543-6445
Email
KCADENHEAD@UCSD.EDU
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristin Cadenhead, MD
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
Facility Information:
Facility Name
UC San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristin Cadenhead, MD
Phone
619-543-6445
Email
kcadenhead@health.ucsd.edu
First Name & Middle Initial & Last Name & Degree
Heline Mirzakhanian, PhD
Phone
619-543-7745
Email
hmirzakhanian@health.ucsd.edu
Facility Name
University of California, San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tracy Alderman, PhD
Phone
619-543-7761
Email
talderman@ucsd.edu
First Name & Middle Initial & Last Name & Degree
Kristin S Cadenhead, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Effects of Cannabidiol (CBD) Versus Placebo as an Adjunct to Treatment in Early Psychosis

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