Cannabidiol as an Adjunctive Treatment for Bipolar Depression (CBDBD)

• ClinicalTrials.gov Identifier: NCT03310593
• Recruitment Status: Terminated
• First Posted: October 16, 2017
• Last Update Posted: July 2, 2021
• Sponsor: Hospital de Clinicas de Porto Alegre
• Collaborators: Federal University of Rio Grande do Sul; University of Sao Paulo
• Information provided by (Responsible Party): Hospital de Clinicas de Porto Alegre

Tracking Information

• First Submitted Date: June 15, 2017
• First Posted Date: October 16, 2017
• Last Update Posted Date: July 2, 2021
• Actual Study Start Date: November 1, 2017
• Actual Primary Completion Date: February 24, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 14, 2018)

Change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) scores. [ Time Frame: 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.

Original Primary Outcome Measures (submitted: October 13, 2017)

Change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) scores. [ Time Frame: Up to 12 weeks ]

Change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) scores.

Current Secondary Outcome Measures (submitted: December 14, 2018)

• Improvement in clinical global impression. [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: Up to weeks 08 and 12 ]
  Change in brain-derived neurotrophic factor (BDNF) levels in the blood.
• Change in inflammatory levels in the blood. [ Time Frame: 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. [ Time Frame: Up to weeks 08 and 12 ]
  Change in endocannabinoid levels in the blood (anandamide and 2-arachidonoylglycerol).
• Remission of manic symptoms. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: Up to weeks 08 and 12 ]
  Change in oxidative stress markers levels in the blood.

Original Secondary Outcome Measures (submitted: October 13, 2017)

• Improvement in clinical global impression. [ Time Frame: Up to 12 weeks ]
  Change from baseline in Clinical Global Impression(CGI-BP) scores.
• Improvement in anxiety symptoms [ Time Frame: Up to 12 weeks ]
  Change from baseline in Hamilton Anxiety Rating Scale (HAMA).
• Improvement in functioning. [ Time Frame: Up to 12 weeks ]
  Change from baseline Functioning Assessment Short Test (FAST) scores.
• Improvement in biological rhythms. [ Time Frame: Up to 12 weeks ]
  Improvement in biological rhythms according to Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN).
• Change in BDNF levels in the blood. [ Time Frame: Up to 12 weeks ]
  Change in brain-derived neurotrophic factor (BDNF) levels in the blood.
• Change in inflammatory levels in the blood. [ Time Frame: Up to 12 weeks ]
  Change in inflammatory levels in the blood (cytokines, chemokines and C-reactive protein).
• Change in endocannabinoid levels in the blood. [ Time Frame: Up to 12 weeks ]
  Change in endocannabinoid levels in the blood.(anandamide and 2-arachidonoylglycerol).
• Remission of manic symptoms. [ Time Frame: Up to 12 weeks ]
  Change from baseline in the Young Mania Rating Scale (YMRS) score.
• Change in depressive symptoms [ Time Frame: Up to 12 weeks ]
  Change from baseline in Hamilton Depression Rating Scale (HAMD) score and in Patient Health Questionnaire (PHQ-9).
• Change in psychotic symptoms [ Time Frame: Up to 12 weeks ]
  Change from baseline in Brief Psychiatric Rating Scale (BPRS) score.
• Change in depressive symptoms [ Time Frame: Up to 12 weeks ]
  Change from baseline in Patient Health Questionnaire (PHQ-9) score.

Current Other Pre-specified Outcome Measures (submitted: December 14, 2018)

Side effects [ Time Frame: 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.

Original Other Pre-specified Outcome Measures (submitted: October 13, 2017)

Side effects [ Time Frame: Up to 12 weeks ]

Evaluation of side effects according Udvalg for Kliniske Undersogelser (UKU) side effects rating scale.

Descriptive Information

• Brief Title: Cannabidiol as an Adjunctive Treatment for Bipolar Depression
• Official Title: A Double-blind, Randomized, Placebo-controlled Clinical Trial of Adjunctive Cannabidiol for Bipolar Depression

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Double-blind, randomized and placebo controlled study

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition

• Bipolar Disorder
• Bipolar Depression
• Bipolar Affective Disorder

Intervention

• Drug: Cannabidiol
  Cannabidiol as active intervention.
• Drug: Placebo
  Placebo intervention.

Study Arms

• Experimental: Cannabidiol
  Cannabidiol 150-300mg per day for 12 weeks.
  Intervention: Drug: Cannabidiol
• Placebo Comparator: Placebo
  Cannabidiol comparator for 12 weeks.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 30, 2021): 36
• Original Estimated Enrollment (submitted: October 13, 2017): 100
• Actual Study Completion Date: March 24, 2020
• Actual Primary Completion Date: February 24, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT03310593
• Other Study ID Numbers: 63811317300005327
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Hospital de Clinicas de Porto Alegre
• Original Responsible Party: Same as current
• Current Study Sponsor: Hospital de Clinicas de Porto Alegre
• Original Study Sponsor: Same as current

Collaborators

• Federal University of Rio Grande do Sul
• University of Sao Paulo

Investigators

• Study Chair: Márcia Kauer-Sant'Anna, MD, PhD; Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre

• PRS Account: Hospital de Clinicas de Porto Alegre
• Verification Date: June 2021