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

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ClinicalTrials.gov Identifier: NCT05041647
Recruitment Status : Not yet recruiting
First Posted : September 13, 2021
Last Update Posted : September 13, 2021
Sponsor:
Collaborator:
McMaster University
Information provided by (Responsible Party):
Benicio Frey, St. Joseph's Healthcare Hamilton

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.

Condition or disease Intervention/treatment Phase
Insomnia Depressive Disorder, Major Sleep Disorder Depression Insomnia Chronic Drug: 25:1 CBD/THC Drug: 5:1 CBD/THC Other: Placebo Phase 2

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 (Broyd et al., 2016). 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 (Babson et al., 2017; Gates et al., 2014; Kuhathasan et al., 2019).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study will be a pilot, three-arm, randomized, double-blind, placebo-controlled trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes 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.
Primary Purpose: Treatment
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
Estimated Study Start Date : December 1, 2021
Estimated Primary Completion Date : November 30, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: High CBD [25:1]
  • 1 dose (1 mL) of HIGH CBD
  • 50 mg/ml CBD and 2 mg/ ml THC
Drug: 25:1 CBD/THC
  • 1 dose (1 mL) of HIGH CBD
  • 50 mg/ml CBD and 2 mg/ ml THC
Other Name: High CBD

Experimental: Low CBD [5:1]
  • 1 dose (1 mL) of LOW CBD
  • 10 mg/ml CBD and 2 mg/ ml THC
Drug: 5:1 CBD/THC
  • 1 dose (1 mL) of LOW CBD
  • 10 mg/ml CBD and 2 mg/ ml THC
Other Name: Low CBD

Placebo Comparator: Placebo
  • 1 dose (1 mL) of PLACEBO
  • No active ingredients
Other: Placebo
  • 1 dose (1 mL) of PLACEBO
  • No active ingredients




Primary Outcome Measures :
  1. Recruitment Rate [ Time Frame: 1 year, at the completion of the study ]
    Rates > 80% using descriptive statistics

  2. Retention Rate [ Time Frame: 1 year, at the completion of the study ]
    Rates > 80% using descriptive statistics


Secondary Outcome Measures :
  1. Sleep latency onset and wake after sleep onset [ Time Frame: through study completion, an average of 4 weeks ]
    Decrease in time (minutes) as measured using actigraphy

  2. Treatment compliance [ Time Frame: through study completion, an average of 4 weeks ]
    Completion rate > 80% using descriptive statistics


Other Outcome Measures:
  1. Self-Reported Sleep Quality [ Time Frame: through study completion, an average of 4 weeks ]
    A measure of self-reported sleep quality via questionnaires and sleep diaries

  2. Cognitive Functioning [ Time Frame: through study completion, an average of 4 weeks ]
    Battery of cognitive function that cover cognitive domains associated with insomnia and cannabis use.

  3. Mean THC/CBD Dosing [ Time Frame: through study completion, an average of 4 weeks ]
    Average THC and CBD dosage with the most optimal trade-off between efficacy and tolerability

  4. Health-Related Quality of Life (HRQoL) [ Time Frame: through study completion, an average of 4 weeks ]
    Short questionnaire to evaluate five dimensions of Health-Related Quality of Life

  5. Healthcare Resource Utilization and Work Productivity [ Time Frame: through study completion, an average of 4 weeks ]
    Short questionnaires to capture economic resource utilization and work productivity



Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. 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)
  2. Diagnosis of MDD according to the Structured Clinical Interview for DSM-5 (SCID-5) 37
  3. 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)
  4. Participant must be willing and able to complete self-reported assessments, including having sufficient fluency in English
  5. Participant must be willing to wear a wrist-worn actiwatch device
  6. 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

  1. 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
  2. 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
  3. Current use of benzodiazepines or any other sleep aids
  4. Positive screening for drugs of abuse including but not limited to opioids, cannabis, benzodiazepines, cocaine, and/or amphetamines (except prescribed stimulants for comorbid ADHD)
  5. 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)
  6. Presence of unstable medical conditions
  7. 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
  8. Allergy to cannabis or any components of the cannabis treatment (including terpenes)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05041647


Contacts
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Contact: Nirushi Kuhathasan, HBSc (905) 522-1155 ext 34317 kuhathn@mcmaster.ca
Contact: Benicio Frey, MD, MSc, PhD (905) 522-1155 ext 33605 freybn@mcmaster.ca

Sponsors and Collaborators
St. Joseph's Healthcare Hamilton
McMaster University
Investigators
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Principal Investigator: Benicio N Frey, MD, MSc, PhD St. Joseph's Healthcare Hamilton
Publications:
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Responsible Party: Benicio Frey, Professor of Psychiatry and Behavioural Neurosciences, Prinicipal Investigator, St. Joseph's Healthcare Hamilton
ClinicalTrials.gov Identifier: NCT05041647    
Other Study ID Numbers: CANMDD001
First Posted: September 13, 2021    Key Record Dates
Last Update Posted: September 13, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Benicio Frey, St. Joseph's Healthcare Hamilton:
Mental Health
Cognition
Sleep Disorders
Major Depressive Disorder
Chronic Insomnia
Cannabis
Additional relevant MeSH terms:
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Sleep Initiation and Maintenance Disorders
Sleep Wake Disorders
Parasomnias
Disease
Depression
Depressive Disorder
Depressive Disorder, Major
Pathologic Processes
Behavioral Symptoms
Mood Disorders
Mental Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Nervous System Diseases
Neurologic Manifestations
Dronabinol
Hallucinogens
Physiological Effects of Drugs
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Cannabinoid Receptor Agonists
Cannabinoid Receptor Modulators
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists