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Cannabinoids as a Treatment for Insomnia in Major Depression (CANMDD)

Primary Purpose

Insomnia, Depressive Disorder, Major, Sleep Disorder

Status

Recruiting

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

25:1 CBD/THC

5:1 CBD/THC

Placebo

About this trial

This is an interventional treatment trial for Insomnia focused on measuring Mental Health, Cognition, Sleep Disorders, Major Depressive Disorder, Chronic Insomnia, Cannabis

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

Age 19 or above (A minimal age of 19 was chosen in order to align with the cannabis legalization rules of the Province of Ontario, where the research participants will be recruited from: https://www.ontario.ca/page/cannabis-legalization#section-1)
Diagnosis of MDD according to the Structured Clinical Interview for DSM-5 (SCID-5) 37
Diagnosis of Insomnia Disorder according to the Duke Structured Interview for Sleep Disorders 38 Patient Health Questionnaire (PHQ-9) 39 score of <10, indicating severity of mild-to-no depression (This criterion is important because a proper diagnosis of current co-morbid insomnia disorder cannot be accurately ascertained during acute major depressive episodes)
Participant must be willing and able to complete self-reported assessments, including having sufficient fluency in English
Participant must be willing to wear a wrist-worn actiwatch device
Participants may be using psychotropic medications for treatment of depression, except benzodiazepines or any other sleep aids, as long as the dosage remains the same from a minimum of 2 months prior to study enrolment until the end of the study (This criterion is important because many individuals with MDD use antidepressant agents and this criterion would make the results more generalizable and useful in real life clinical practice)

Exclusion Criteria

Lifetime diagnosis of Schizophrenia, Bipolar Disorder or any other psychotic disorder, as well as current or recent (last 6 months) Alcohol or Substance Use Disorder according to the SCID-5
Individuals with current diagnosis of Generalized Anxiety Disorder, Panic Disorder, Obsessive-Compulsive Disorder, Post-Traumatic Stress Disorder or Eating Disorder will be excluded because these psychiatric disorders are associated with sleep disturbance; however, because of the high rates of co-morbid psychiatric conditions in MDD lifetime/past diagnosis will be allowed in order for the results to be generalizable and useful in real life clinical practice
Current use of benzodiazepines or any other sleep aids
Positive screening for drugs of abuse including but not limited to opioids, cannabis, benzodiazepines, cocaine, and/or amphetamines (except prescribed stimulants for comorbid ADHD)
Presence of any sleep disorder other than insomnia that is considered the primary diagnosis, determined by the Duke Structured Interview for Sleep Disorders (e.g. Sleep Apnea, Limb Movement Disorder, or Circadian Rhythm Disorders)
Presence of unstable medical conditions
Pregnancy or breastfeeding (female participants will need to agree to use an acceptable contraceptive method during the study because of potential unknown teratogenic effects of cannabinoids
Allergy to cannabis or any components of the cannabis treatment (including terpenes)

Sites / Locations

St. Joseph's Healthcare HamiltonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

High CBD [25:1]

Low CBD [5:1]

Placebo

Arm Description

1 dose (1 mL) of HIGH CBD 50 mg/ml CBD and 2 mg/ ml THC

1 dose (1 mL) of LOW CBD 10 mg/ml CBD and 2 mg/ ml THC

1 dose (1 mL) of PLACEBO No active ingredients

Outcomes

Primary Outcome Measures

Recruitment Rate

Rates > 80% using descriptive statistics

Retention Rate

Rates > 80% using descriptive statistics

Secondary Outcome Measures

Sleep latency onset and wake after sleep onset

Change in time (minutes) as measured using actigraphy

Treatment compliance

Completion rate > 80% using descriptive statistics

Full Information

NCT ID

NCT05041647

First Posted

July 14, 2021

Last Updated

September 6, 2023

Sponsor

St. Joseph's Healthcare Hamilton

Collaborators

McMaster University

1. Study Identification

Unique Protocol Identification Number

NCT05041647

Brief Title

Cannabinoids as a Treatment for Insomnia in Major Depression

Acronym

CANMDD

Official Title

A Pilot, Double-Blind, Randomized, Placebo-Controlled Trial Evaluating the Efficacy and Safety of a Cannabis-Infused Oil For Treatment of Insomnia in Major Depression

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 28, 2023 (Actual)

Primary Completion Date

March 31, 2024 (Anticipated)

Study Completion Date

June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

St. Joseph's Healthcare Hamilton

Collaborators

McMaster University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This single-site study is a pilot, three-armed, double-blinded, placebo-controlled randomized controlled trial (RCT) that will determine the feasibility of a definitive RCT investigating the use of cannabis oil as a treatment for insomnia in individuals with MDD. The study will also determine whether standard THC with higher CBD vs lower CBD has a differential impact on insomnia. The study will also analyze other important objective parameters of sleep including total sleep time and sleep efficiency from actigraphy data. Polysomnography data will also be analyzed. In addition, standardized, validated instruments will be used to collect data on severity of depressive symptoms, cognitive functioning biological rhythm disruption, daytime sleepiness, health-related quality of life (HRQoL), healthcare resource utilization, work productivity and activity impairment, as well as other side effects, in order to better understand the potential impact of the use of cannabis oil on these important health outcomes.

Detailed Description

The study will be a three-arm, randomized, double-blind, placebo-controlled trial. The study population will include 60 males and females, ages 19 and older, who report chronic problems with insomnia at least three times per week for at least three months and have a diagnosis of co-morbid MDD. Eligible participants will complete a urine screen for drugs of abuse including opioids, cannabis, benzodiazepines and amphetamines before treatment randomization. Participants with a positive screen for any of these drugs of abuse will be excluded from the study. If the drug screen is negative, the principal investigator will assess patient health history and perform a physical examination. All study participants must be able to fully understand the study procedures and must sign a research ethics board (REB)-approved informed consent before study entry. A neuropsychological battery will be used to assess cognitive function in the domains of attention, verbal memory, psychomotor functioning, and executive functioning at baseline and at the end of the 4-week treatment in order to examine possible cognitive benefits or side effects from the treatment. These cognitive domains were chosen because these domains are known to be negatively affected by chronic insomnia and by cannabis use. Patients will also complete a series of clinician-rated and self-reported questionnaires. During the 4-week treatment period, participants will be instructed to start treatment with a single, dose of oil at bedtime. Each dose will have either 50 mg/ml CBD and 2 mg/ml THC (High CBD arm; MLP-001) or 10 mg/ml CBD and 2 mg/ml THC (Low CBD arm; MLP-002). Non-responding study participants will add 1 additional dose to their respective treatment after 2 weeks if a higher dosage is needed based on an Insomnia Severity Index (ISI) reduction of >8 points and tolerability (side effects). Responding participants will continue with 1 dose of their treatment after 2 weeks. This dose range is based on previous studies showing that the effective dosage of THC to improve sleep ranged, on average, between 5 and 15 mg daily.

6. Conditions and Keywords

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

Insomnia, Depressive Disorder, Major, Sleep Disorder, Depression, Insomnia Chronic

Keywords

Mental Health, Cognition, Sleep Disorders, Major Depressive Disorder, Chronic Insomnia, Cannabis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

The study will be a pilot, three-arm, randomized, double-blind, placebo-controlled trial.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Study participants will be randomly assigned in a 1:1:1 manner to one of the three treatment arms using a computer-generated, permuted-block randomization schedule. Randomization will be stratified by sex. All of the treating physicians who will be also administering the clinical questionnaires, the trained graduate student conducting cognitive testing, as well as any other trial staff, will be blinded to the subjects' status until the end of the study.

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

High CBD [25:1]

Arm Type

Experimental

Arm Description

1 dose (1 mL) of HIGH CBD 50 mg/ml CBD and 2 mg/ ml THC

Arm Title

Low CBD [5:1]

Arm Type

Experimental

Arm Description

1 dose (1 mL) of LOW CBD 10 mg/ml CBD and 2 mg/ ml THC

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

1 dose (1 mL) of PLACEBO No active ingredients

Intervention Type

Drug

Intervention Name(s)

25:1 CBD/THC

Other Intervention Name(s)

High CBD

Intervention Description

1 dose (1 mL) of HIGH CBD 50 mg/ml CBD and 2 mg/ ml THC

Intervention Type

Drug

Intervention Name(s)

5:1 CBD/THC

Other Intervention Name(s)

Low CBD

Intervention Description

1 dose (1 mL) of LOW CBD 10 mg/ml CBD and 2 mg/ ml THC

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

1 dose (1 mL) of PLACEBO No active ingredients

Primary Outcome Measure Information:

Title

Recruitment Rate

Description

Rates > 80% using descriptive statistics

Time Frame

1 year, at the completion of the study

Title

Retention Rate

Description

Rates > 80% using descriptive statistics

Time Frame

1 year, at the completion of the study

Secondary Outcome Measure Information:

Title

Sleep latency onset and wake after sleep onset

Description

Change in time (minutes) as measured using actigraphy

Time Frame

through study completion, an average of 4 weeks

Title

Treatment compliance

Description

Completion rate > 80% using descriptive statistics

Time Frame

through study completion, an average of 4 weeks

Other Pre-specified Outcome Measures:

Title

Self-Reported Sleep Quality

Description

A measure of self-reported sleep quality via questionnaires and sleep diaries

Time Frame

through study completion, an average of 4 weeks

Title

Cognitive Functioning

Description

Battery of cognitive function that cover cognitive domains associated with insomnia and cannabis use.

Time Frame

through study completion, an average of 4 weeks

Title

Mean THC/CBD Dosing

Description

Average THC and CBD dosage with the most optimal trade-off between efficacy and tolerability

Time Frame

through study completion, an average of 4 weeks

Title

Health-Related Quality of Life (HRQoL)

Description

Short questionnaire to evaluate five dimensions of Health-Related Quality of Life

Time Frame

through study completion, an average of 4 weeks

Title

Healthcare Resource Utilization and Work Productivity

Description

Short questionnaires to capture economic resource utilization and work productivity

Time Frame

through study completion, an average of 4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria Age 19 or above (A minimal age of 19 was chosen in order to align with the cannabis legalization rules of the Province of Ontario, where the research participants will be recruited from: https://www.ontario.ca/page/cannabis-legalization#section-1) Diagnosis of MDD according to the Structured Clinical Interview for DSM-5 (SCID-5) 37 Diagnosis of Insomnia Disorder according to the Duke Structured Interview for Sleep Disorders 38 Patient Health Questionnaire (PHQ-9) 39 score of <10, indicating severity of mild-to-no depression (This criterion is important because a proper diagnosis of current co-morbid insomnia disorder cannot be accurately ascertained during acute major depressive episodes) Participant must be willing and able to complete self-reported assessments, including having sufficient fluency in English Participant must be willing to wear a wrist-worn actiwatch device Participants may be using psychotropic medications for treatment of depression, except benzodiazepines or any other sleep aids, as long as the dosage remains the same from a minimum of 2 months prior to study enrolment until the end of the study (This criterion is important because many individuals with MDD use antidepressant agents and this criterion would make the results more generalizable and useful in real life clinical practice) Exclusion Criteria Lifetime diagnosis of Schizophrenia, Bipolar Disorder or any other psychotic disorder, as well as current or recent (last 6 months) Alcohol or Substance Use Disorder according to the SCID-5 Individuals with current diagnosis of Generalized Anxiety Disorder, Panic Disorder, Obsessive-Compulsive Disorder, Post-Traumatic Stress Disorder or Eating Disorder will be excluded because these psychiatric disorders are associated with sleep disturbance; however, because of the high rates of co-morbid psychiatric conditions in MDD lifetime/past diagnosis will be allowed in order for the results to be generalizable and useful in real life clinical practice Current use of benzodiazepines or any other sleep aids Positive screening for drugs of abuse including but not limited to opioids, cannabis, benzodiazepines, cocaine, and/or amphetamines (except prescribed stimulants for comorbid ADHD) Presence of any sleep disorder other than insomnia that is considered the primary diagnosis, determined by the Duke Structured Interview for Sleep Disorders (e.g. Sleep Apnea, Limb Movement Disorder, or Circadian Rhythm Disorders) Presence of unstable medical conditions Pregnancy or breastfeeding (female participants will need to agree to use an acceptable contraceptive method during the study because of potential unknown teratogenic effects of cannabinoids Allergy to cannabis or any components of the cannabis treatment (including terpenes)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Abbey Schlatman

Phone

(905) 522-1155

Ext

36737

aschlatm@stjosham.on.ca

First Name & Middle Initial & Last Name or Official Title & Degree

Benicio Frey, MD, MSc, PhD

Phone

(905) 522-1155

Ext

33605

freybn@mcmaster.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Benicio N Frey, MD, MSc, PhD

Organizational Affiliation

St. Joseph's Healthcare Hamilton

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Nirushi Kuhathasan, PhD

Organizational Affiliation

St. Joseph's Healthcare Hamilton

Official's Role

Study Chair

Facility Information:

Facility Name

St. Joseph's Healthcare Hamilton

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L9C 0E3

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Benicio Frey, MD

Phone

905-522-1155

Ext

33605

freybn@mcmaster.ca

First Name & Middle Initial & Last Name & Degree

Abbey Schlatman, BSc

Phone

905-522-1155

Ext

36737

aschlatm@stjoes.ca

First Name & Middle Initial & Last Name & Degree

Benicio Frey, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

26858214

Citation

Broyd SJ, van Hell HH, Beale C, Yucel M, Solowij N. Acute and Chronic Effects of Cannabinoids on Human Cognition-A Systematic Review. Biol Psychiatry. 2016 Apr 1;79(7):557-67. doi: 10.1016/j.biopsych.2015.12.002. Epub 2015 Dec 8.

Results Reference

background

PubMed Identifier

28349316

Citation

Babson KA, Sottile J, Morabito D. Cannabis, Cannabinoids, and Sleep: a Review of the Literature. Curr Psychiatry Rep. 2017 Apr;19(4):23. doi: 10.1007/s11920-017-0775-9.

Results Reference

background

PubMed Identifier

24726015

Citation

Gates PJ, Albertella L, Copeland J. The effects of cannabinoid administration on sleep: a systematic review of human studies. Sleep Med Rev. 2014 Dec;18(6):477-87. doi: 10.1016/j.smrv.2014.02.005. Epub 2014 Mar 7.

Results Reference

background

PubMed Identifier

31120284

Citation

Kuhathasan N, Dufort A, MacKillop J, Gottschalk R, Minuzzi L, Frey BN. The use of cannabinoids for sleep: A critical review on clinical trials. Exp Clin Psychopharmacol. 2019 Aug;27(4):383-401. doi: 10.1037/pha0000285. Epub 2019 May 23.

Results Reference

background

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Cannabinoids as a Treatment for Insomnia in Major Depression

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