Cannabidiol as an Adjunctive Treatment for Bipolar Depression (CBDBD)
Primary Purpose
Bipolar Disorder, Bipolar Depression, Bipolar Affective Disorder
Status
Terminated
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Cannabidiol
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Bipolar Disorder focused on measuring bipolar disorder, bipolar depression, cannabidiol, endocannabinoids
Eligibility Criteria
Inclusion Criteria:
- Major depressive episode as part of bipolar I disorder or bipolar II disorder according to Fifth Edition of Diagnostic and Statistical Manual for Mental Disorders (DSM-5) and are able to provide written informed consent.
- Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 12 and MADRS items 1 (Apparent Sadness) and 2 (Reported Sadness) scores ≥ 2 at baseline.
- Young Mania Rating Scale (YMRS) ≤ 11.
- Currently prescribed lithium or valproic acid and derivates (divalproex sodium, sodium valproate) or atypical antipsychotics at therapeutic dosage for at least 04 weeks before the baseline.
- Females must test negative for pregnancy and must be using adequate birth control measures throughout the study.
Exclusion Criteria:
- Another concurrent mental or behavioral disorder that requires psychiatric attention in the past 6 months.
- Young Mania Rating Scale (YMRS) score > 12.
- Current or past drug sensitivity/intolerance to cannabidiol.
- Substance Use Disorder according to DSM-5 within past 6 months, except for nicotine Substance Use Disorder.
- Clinically significant unstable medical illness, neurological disorders or inflammatory/autoimmune diseases.
- Any autoimmune, inflammatory or neurologic disorders that requires treatment with steroidal anti-inflammatory medications or immunotherapy with biologic drugs.
- Actively suicidal or homicidal risk.
- Females who are pregnant or breastfeeding
Sites / Locations
- Hospital de Clínicas de Porto Alegre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Cannabidiol
Placebo
Arm Description
Cannabidiol 150-300mg per day for 12 weeks.
Cannabidiol comparator for 12 weeks.
Outcomes
Primary Outcome Measures
Change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) scores.
Change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) scores.
Scale range: from 0 to 60.
Higher values represent more severe symptoms of depression.
Secondary Outcome Measures
Improvement in clinical global impression.
Change from baseline in Clinical Global Impression(CGI-BP) scores.
Scale range: from 1 to 7.
Higher values represent more severe symptoms of bipolar disorder.
Improvement in anxiety symptoms
Change from baseline in Hamilton Anxiety Rating Scale (HAMA).
Scale range: from 0 to 56.
Higher values represent more severe symptoms of anxiety.
Improvement in functioning.
Change from baseline Functioning Assessment Short Test (FAST) scores.
Scale range: from 0 to 72.
Higher values represent more severe functional impairment.
Improvement in biological rhythms.
Improvement in biological rhythms according to Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN).
Scale range: from 0 to 88.
Higher values represent more severe symptoms of biological rhythms.
Change in BDNF levels in the blood.
Change in brain-derived neurotrophic factor (BDNF) levels in the blood.
Change in inflammatory levels in the blood.
Change in inflammatory levels in the blood (cytokines, chemokines and C-reactive protein).
Change in endocannabinoid levels in the blood.
Change in endocannabinoid levels in the blood (anandamide and 2-arachidonoylglycerol).
Remission of manic symptoms.
Change from baseline in the Young Mania Rating Scale (YMRS) score.
Scale range: from 0 to 58.
Higher values represent more severe symptoms of mania.
Change in depressive symptoms
Change from baseline in Hamilton Depression Rating Scale (HAMD) score.
Scale range: from 0 to 52.
Higher values represent more severe symptoms of depression.
Change in psychotic symptoms
Change from baseline in Brief Psychiatric Rating Scale (BPRS) score.
Scale range: from 0 to 108.
Higher values represent more severe symptoms of psychosis.
Change in depressive symptoms according to MADRS
Higher values represent more severe symptoms of depression.
Scale range: from 0 to 60.
Change in depressive symptoms according to PHQ-9
Change from baseline in Patient Health Questionnaire (PHQ-9) score.
Scale range: from 0 to 27.
Change in oxidative stress markers levels in the blood.
Change in oxidative stress markers levels in the blood.
Full Information
NCT ID
NCT03310593
First Posted
June 15, 2017
Last Updated
June 30, 2021
Sponsor
Hospital de Clinicas de Porto Alegre
Collaborators
Federal University of Rio Grande do Sul, University of Sao Paulo
1. Study Identification
Unique Protocol Identification Number
NCT03310593
Brief Title
Cannabidiol as an Adjunctive Treatment for Bipolar Depression
Acronym
CBDBD
Official Title
A Double-blind, Randomized, Placebo-controlled Clinical Trial of Adjunctive Cannabidiol for Bipolar Depression
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Terminated
Why Stopped
It was interrupted due to the coronavirus pandemic outbreak.
Study Start Date
November 1, 2017 (Actual)
Primary Completion Date
February 24, 2020 (Actual)
Study Completion Date
March 24, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital de Clinicas de Porto Alegre
Collaborators
Federal University of Rio Grande do Sul, University of Sao Paulo
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
Depressive symptoms are associated with significant psychosocial impairment. However, current treatments of bipolar depression are only partially effective.
Cannabidiol is a natural component of cannabis without psychotomimetic or addictive properties. Cannabidiol has been shown to produce therapeutic effects including anticonvulsive, anxiolytic, antipsychotic and neuroprotective effects. The investigators hypothesize that treatment with cannabidiol will result in improvement of depressive and anxiety symptoms, as well as, improvement in functioning and inflammatory biomarkers. During the clinical trial, subjects will receive study medication (cannabidiol 150-300mg/day) or placebo for a period of 12 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder, Bipolar Depression, Bipolar Affective Disorder
Keywords
bipolar disorder, bipolar depression, cannabidiol, endocannabinoids
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Double-blind, randomized and placebo controlled study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cannabidiol
Arm Type
Experimental
Arm Description
Cannabidiol 150-300mg per day for 12 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Cannabidiol comparator for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Cannabidiol
Intervention Description
Cannabidiol as active intervention.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo intervention.
Primary Outcome Measure Information:
Title
Change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) scores.
Description
Change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) scores.
Scale range: from 0 to 60.
Higher values represent more severe symptoms of depression.
Time Frame
08 weeks
Secondary Outcome Measure Information:
Title
Improvement in clinical global impression.
Description
Change from baseline in Clinical Global Impression(CGI-BP) scores.
Scale range: from 1 to 7.
Higher values represent more severe symptoms of bipolar disorder.
Time Frame
Up to weeks 08 and 12
Title
Improvement in anxiety symptoms
Description
Change from baseline in Hamilton Anxiety Rating Scale (HAMA).
Scale range: from 0 to 56.
Higher values represent more severe symptoms of anxiety.
Time Frame
Up to weeks 08 and 12
Title
Improvement in functioning.
Description
Change from baseline Functioning Assessment Short Test (FAST) scores.
Scale range: from 0 to 72.
Higher values represent more severe functional impairment.
Time Frame
Up to weeks 08 and 12
Title
Improvement in biological rhythms.
Description
Improvement in biological rhythms according to Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN).
Scale range: from 0 to 88.
Higher values represent more severe symptoms of biological rhythms.
Time Frame
Up to weeks 08 and 12
Title
Change in BDNF levels in the blood.
Description
Change in brain-derived neurotrophic factor (BDNF) levels in the blood.
Time Frame
Up to weeks 08 and 12
Title
Change in inflammatory levels in the blood.
Description
Change in inflammatory levels in the blood (cytokines, chemokines and C-reactive protein).
Time Frame
Up to weeks 08 and 12
Title
Change in endocannabinoid levels in the blood.
Description
Change in endocannabinoid levels in the blood (anandamide and 2-arachidonoylglycerol).
Time Frame
Up to weeks 08 and 12
Title
Remission of manic symptoms.
Description
Change from baseline in the Young Mania Rating Scale (YMRS) score.
Scale range: from 0 to 58.
Higher values represent more severe symptoms of mania.
Time Frame
Up to weeks 08 and 12
Title
Change in depressive symptoms
Description
Change from baseline in Hamilton Depression Rating Scale (HAMD) score.
Scale range: from 0 to 52.
Higher values represent more severe symptoms of depression.
Time Frame
Up to weeks 08 and 12
Title
Change in psychotic symptoms
Description
Change from baseline in Brief Psychiatric Rating Scale (BPRS) score.
Scale range: from 0 to 108.
Higher values represent more severe symptoms of psychosis.
Time Frame
Up to weeks 08 and 12
Title
Change in depressive symptoms according to MADRS
Description
Higher values represent more severe symptoms of depression.
Scale range: from 0 to 60.
Time Frame
Up to week 12
Title
Change in depressive symptoms according to PHQ-9
Description
Change from baseline in Patient Health Questionnaire (PHQ-9) score.
Scale range: from 0 to 27.
Time Frame
Up to weeks 08 and 12
Title
Change in oxidative stress markers levels in the blood.
Description
Change in oxidative stress markers levels in the blood.
Time Frame
Up to weeks 08 and 12
Other Pre-specified Outcome Measures:
Title
Side effects
Description
Evaluation of side effects according Udvalg for Kliniske Undersogelser (UKU) side effects rating scale.
Scale range: from 0 to 144.
Higher values represent more severe side effects associated to medications.
Time Frame
Up to weeks 08 and 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Major depressive episode as part of bipolar I disorder or bipolar II disorder according to Fifth Edition of Diagnostic and Statistical Manual for Mental Disorders (DSM-5) and are able to provide written informed consent.
Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 12 and MADRS items 1 (Apparent Sadness) and 2 (Reported Sadness) scores ≥ 2 at baseline.
Young Mania Rating Scale (YMRS) ≤ 11.
Currently prescribed lithium or valproic acid and derivates (divalproex sodium, sodium valproate) or atypical antipsychotics at therapeutic dosage for at least 04 weeks before the baseline.
Females must test negative for pregnancy and must be using adequate birth control measures throughout the study.
Exclusion Criteria:
Another concurrent mental or behavioral disorder that requires psychiatric attention in the past 6 months.
Young Mania Rating Scale (YMRS) score > 12.
Current or past drug sensitivity/intolerance to cannabidiol.
Substance Use Disorder according to DSM-5 within past 6 months, except for nicotine Substance Use Disorder.
Clinically significant unstable medical illness, neurological disorders or inflammatory/autoimmune diseases.
Any autoimmune, inflammatory or neurologic disorders that requires treatment with steroidal anti-inflammatory medications or immunotherapy with biologic drugs.
Actively suicidal or homicidal risk.
Females who are pregnant or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Márcia Kauer-Sant'Anna, MD, PhD
Organizational Affiliation
Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital de Clínicas de Porto Alegre
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90035-903
Country
Brazil
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Cannabidiol as an Adjunctive Treatment for Bipolar Depression
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