| CTRI Number |
CTRI/2025/05/087476 [Registered on: 23/05/2025] Trial Registered Prospectively |
| Last Modified On: |
22/05/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Can cannabidiol help in the treatment of depression in patients with bipolar disorder? |
|
Scientific Title of Study
|
Cannabidiol Adjunctive Therapy for Acute Bipolar Depression: A Randomized Double-Blind, Placebo Controlled Trial |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
YC Janardhan Reddy |
| Designation |
Senior Professor |
| Affiliation |
National Institute of Mental Health and Neuro Science (NIMHANS) |
| Address |
Department of Psychiatry
National Institute of Mental Health and Neuro Science (NIMHANS), Bengaluru
Bangalore
KARNATAKA
560029
India |
| Phone |
0802995278 |
| Fax |
|
| Email |
ycjreddy@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
YC Janardhan Reddy |
| Designation |
Senior Professor |
| Affiliation |
National Institute of Mental Health and Neuro Science (NIMHANS) |
| Address |
Department of Psychiatry
National Institute of Mental Health and Neuro Science (NIMHANS), Bengaluru
Bangalore
KARNATAKA
560029
India |
| Phone |
0802995278 |
| Fax |
|
| Email |
ycjreddy@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
YC Janardhan Reddy |
| Designation |
Senior Professor |
| Affiliation |
National Institute of Mental Health and Neuro Science (NIMHANS) |
| Address |
Department of Psychiatry
National Institute of Mental Health and Neuro Science (NIMHANS), Bengaluru
Bangalore
KARNATAKA
560029
India |
| Phone |
0802995278 |
| Fax |
|
| Email |
ycjreddy@gmail.com |
|
|
Source of Monetary or Material Support
|
| Canadian Institutes of Health Research - primary funder for the study |
| PBG Biopharma, Canada - supplier of cannabidiol and placebo |
|
|
Primary Sponsor
|
| Name |
Canadian Institutes of Health Research |
| Address |
160 Elgin Street, 9th Floor, 4809A Ottawa Ontario K1A0W9 |
| Type of Sponsor |
Government funding agency |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
Canada
India |
|
Sites of Study
|
| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Raman Deep |
All India Institute of Medical Sciences (AIIMS), New Delhi |
Department of Psychiatry, AIIMS, Sri Aurobindo Marg, Ansari Nagar, Ansari Nagar East, New Delhi,
New Delhi
DELHI |
01126588500
drramandeep@gmail.com |
| Nishant Goyal |
Central Institute of Psychiatry, Ranchi |
Department of Psychiatry, CIP, C8MG+V83, Patratoli, Kanke, Jharkhand 834006
Ranchi
JHARKHAND |
06512451115
psynishant@gmail.com |
| Vikas Menon |
Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Puducherry |
Department of Psychiatry, JIPMER, XQ2X+4VC, Jipmer Campus Rd, Jipmer Campus, Puducherry, 605006
Pondicherry
PONDICHERRY |
04132296518
drvmenon@gmail.com |
| Shyam Sundar Arumugham |
National Institute of Mental Health and Neuro Sciences |
Department of Psychiatry, Hosur Road Bengaluru 560029
Bangalore
KARNATAKA |
08026995353
a.shyamsudnar@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| Institute Ethics Committee, All India Institute of Medical Sciences, New Delhi |
Approved |
| Institute Ethics Committee, Central Institute of Psychiatry |
Approved |
| Institutional Ethics Committee-Interventional studies, JIPMER, Puducherry |
Approved |
| NIMHANS Ethics Commiteee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: F313||Bipolar disorder, current episodedepressed, mild or moderate severity, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Cannabidiol |
Cannabidiol capsules 400-600 mg per day for 6 weeks |
| Comparator Agent |
Placebo |
Matching placebo capsules for 6 weeks |
|
|
Inclusion Criteria
|
| Age From |
19.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Both |
| Details |
1. Males or females aged 19 to 70 years (inclusive).
2. DSM-5 diagnosis of BD I or BD II, AND a current major depressive episode confirmed by MINI 7.0.2 .
3. All patients must be taking either a mood stabilizer (i.e. lithium or valproate; lamotrigine monotherapy as a mood stabilizer is acceptable for BD II patients only and not for BD I) OR an atypical antipsychotic OR a combination of these (two mood stabilizers or a mood stabilizer plus an atypical antipsychotic), at therapeutic doses. Medications and therapeutic doses are: lithium, serum level 0.6 to 1.2 mEqL; divalproex/sodium valproate, serum level 350 to 700 uML(45 to 125 mcgml); risperidone 2 to6 mg/day; olanzapine 5 to 30 mg/day; quetiapine IR or XR 300 to 900 mg/day; aripiprazole 10 to 30 mg/day; and ziprasidone 80-160 mg/day. Combinations of these medications as outlined above, or the combination of any of them with lamotrigine 100400 mg daily, or the combination of a mood stabilizer plus asenapine 5 to 20 mg/day are also permitted.
4. Have received a minimum of 6-weeks treatment at adequate doses for treatment of current depressive episode with at least one CANMAT recommended first-line treatment for bipolar I disorder (i.e. lithium, lamotrigine, lurasidone, or quetiapine either as monotherapy or adjunctive therapy), or at least one first or second-line treatment for bipolar II depression (i.e.
a. quetiapine, lithium, lamotrigine, sertraline, or venlafaxine as monotherapy or adjunctive therapy, or bupropion adjunctive therapy).
5. A MADRS score of greater than or equal to 20 and a YMRS score of less than or equal to 12 (these cut off scores are standard in bipolar depression RCTs).
6. Inpatient or outpatient status.
7. All participants are required to agree to practice highly effective methods of contraception (i.e.
a. hormonal contraceptives, intrauterine device or system, vasectomy and tubal ligation, or double barrier methods of contraception) OR agree to completely abstain from heterosexual intercourse. Females who do not have childbearing potential are required to be postmenopausal for at least 1 year before the screening visit (confirmed by an FSH test) OR surgically sterile.
8. The capability of understanding, consenting to and complying with study requirements.
9. All concomitant medication must be at a stable dose for two weeks prior to the randomization visit.
|
|
| ExclusionCriteria |
| Details |
1. Current depressive episode greater than 12 months.
2. A history of rapid cycling, defined as 4 or more mood episodes in the preceding 12 months.
3. Current unstable or inadequately treated medical illness with the exception of current depression.
4. Recently started taking a CANMAT-recommended treatment for the management of acute bipolar depressive episode, but has not had a trial for a minimum of 6 weeks with adequate doses.
5. Recently (i.e. within the past 8 weeks) began structured psychotherapy (i.e. cognitivebehavioral therapy, interpersonal psychotherapy, family-focused therapy, or interpersonal and social rhythm therapy).
6. Current use of stimulant medications.
7. A history of non-response or intolerance to CBD.
8. Current or past month daily use of CBD, or any product or drug that contains CBD.
Occasional users will be included if they agree to refrain from using during the trial.
9. A history of non-response to electroconvulsive therapy for the current depressive episode.
10. A current diagnosis of other primary psychiatric disorders as assessed by a study investigator to be primary and causing greater impairment than BD.
11. A lifetime history of a primary psychotic disorder (e.g. schizoaffective disorder, bipolar subtype) according to DSM-5 criteria.
12. Patients who have met the DSM-5 criteria for a substance use disorder (except for nicotine or caffeine) within the past 6 months.
13. Significant active suicidal ideation (as evidenced by MADRS suicide item score of 4 for more).
14. Pregnancy or lactation.
15. Liver function tests (AST and ALT) three times the upper limit of normal.
|
|
|
Method of Generating Random Sequence
|
Permuted block randomization, variable |
|
Method of Concealment
|
Pharmacy-controlled Randomization |
|
Blinding/Masking
|
Participant, Investigator and Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Improvement in depressive symptoms, as measured by changes in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to week 6. |
week 6 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Response rate |
week 6 |
| Remission rate |
week 6 |
| Treatment emergent manic/hypomanic events |
Week 0- 6 |
| changes in Hamilton Depression Rating Scale 21- item (HAM-D) |
week 6 |
| subjective depressive symptoms as measured by changes in the Quick Inventory of Depressive Symptomatology–Self-report (QIDS-SR) and Dimensional Anhedonia Rating Scale (DARS); |
week 6 |
| anxiety symptoms scores measured objectively with the Hamilton Anxiety Rating Scale (HAM-A), and subjectively with the General Anxiety Disorder-7 (GAD-7) and State-Trait Anxiety Inventory (STAI) |
week 6 |
| global severity of symptoms as indicated by changes in Clinical Global Impressions Scale, Bipolar Version, Severity (CGI-BP-S) and global improvement in symptoms with Clinical Global Impressions Scale, Bipolar Version, Change (CGI-BP-C) |
week 6 |
| psychotic symptoms as reflected by changes in Positive and Negative Symptoms Scale (PANSS scores) |
week 6 |
| Subjective cognitive functioning will be assessed using the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and Patient-Reported Outcomes Measurement Information System (PROMIS), and objective cognitive functioning as measured by Screen for Cognitive Impairment in Psychiatry (SCIP) |
week 6 |
| sleep quality measured by Pittsburgh Sleep Quality Index (PSQI) |
week 6 |
| suicidal thoughts and behaviours as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) |
week 0-6 |
| Quality of life assessed using The Brief Quality of Life in Bipolar Disorder Questionnaire (Brief QoL-BD |
week 6 |
| Daily functioning based on Functioning Assessment Short Test (FAST) |
Week 6 |
| health services utilization by self-report |
week 6 |
| Open ended adverse report form and b) the Frequency, Intensity, Burden of Side Effects Rating scale (FIBSER) |
week 6 |
|
|
Target Sample Size
|
Total Sample Size="360"
Sample Size from India="200"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
01/08/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="5"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
It is a randomized controlled trial comparing cannabidiol vs placebo as an add-on treatment for patients with bipolar disorder, who are currently in a depressive episode and have not responded to an adequate first line treatment. The primary objective of the study is to assess the efficacy, safety and tolerability of adjunctive CBD vs placebo in patients with acute bipolar depression (BD I or BD II) who have not responded to adequate trials with at least one first-line treatment outlined in the most recent CANMAT clinical guidelines for bipolar I disorder (i.e. lithium, quetiapine, lamotrigine, or lurasidone), or at least one first or second-line treatment for bipolar II depression (i.e. quetiapine, lithium, lamotrigine, sertraline, or venlafaxine as monotherapy or adjunctive therapy, or bupropion adjunctive therapy). We plan to recruit 360 study participants globally over 5 years, who will be randomly allocated to receive either cannabidiol or placebo (1:1 ratio) for a period of 6 weeks. The primary efficacy measure for the study is improvement in depressive symptoms, as measured by changes in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to week 6. In addition to periodic structured clinical assessments, the study participants would undergo blood investigations to evaluate biomarkers (multi-omics, cytokines, oxidative stress markers, neurotropins) of treatment response and measure cannabidiol levels at screening and at the end of the study period (6 weeks. |