CBDBD: Cannabidiol as an Adjunctive Treatment for Bipolar Depression

Sponsor

Hospital de Clinicas de Porto Alegre (Other)

Overall Status

Terminated

CT.gov ID

NCT03310593

Collaborator

Federal University of Rio Grande do Sul (Other), University of Sao Paulo (Other)

Enrollment

Location

Arms

28.7

Actual Duration (Months)

1.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder Bipolar Depression Bipolar Affective Disorder	Drug: Cannabidiol Drug: Placebo	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double-blind, randomized and placebo controlled studyDouble-blind, randomized and placebo controlled study

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Double-blind, Randomized, Placebo-controlled Clinical Trial of Adjunctive Cannabidiol for Bipolar Depression

Actual Study Start Date :

Nov 1, 2017

Actual Primary Completion Date :

Feb 24, 2020

Actual Study Completion Date :

Mar 24, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cannabidiol Cannabidiol 150-300mg per day for 12 weeks.	Drug: Cannabidiol Cannabidiol as active intervention.
Placebo Comparator: Placebo Cannabidiol comparator for 12 weeks.	Drug: Placebo Placebo intervention.

Arm

Intervention/Treatment

Experimental: Cannabidiol

Cannabidiol 150-300mg per day for 12 weeks.

Drug: Cannabidiol

Cannabidiol as active intervention.

Placebo Comparator: Placebo

Cannabidiol comparator for 12 weeks.

Drug: Placebo

Placebo intervention.

Outcome Measures

Primary Outcome Measures

Change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) scores. [08 weeks]
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. [Up to weeks 08 and 12]
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 [Up to weeks 08 and 12]
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. [Up to weeks 08 and 12]
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. [Up to weeks 08 and 12]
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. [Up to weeks 08 and 12]
Change in brain-derived neurotrophic factor (BDNF) levels in the blood.
Change in inflammatory levels in the blood. [Up to weeks 08 and 12]
Change in inflammatory levels in the blood (cytokines, chemokines and C-reactive protein).
Change in endocannabinoid levels in the blood. [Up to weeks 08 and 12]
Change in endocannabinoid levels in the blood (anandamide and 2-arachidonoylglycerol).
Remission of manic symptoms. [Up to weeks 08 and 12]
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 [Up to weeks 08 and 12]
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 [Up to weeks 08 and 12]
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 [Up to week 12]
Higher values represent more severe symptoms of depression. Scale range: from 0 to 60.
Change in depressive symptoms according to PHQ-9 [Up to weeks 08 and 12]
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. [Up to weeks 08 and 12]
Change in oxidative stress markers levels in the blood.

Other Outcome Measures

Side effects [Up to weeks 08 and 12]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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