Cannabis as a Complementary Treatment in Multiple Sclerosis (CANSEP)

Efficacy of Cannabinoids to the Current Standard Treatments on Symptom Relief in Persons With Multiple Sclerosis: Randomized Controlled Trial

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) afflicting over 77,000 Canadians. Unfortunately, the therapeutic arsenal to relieve MS symptoms is limited. It is therefore essential to develop better approaches to treat the symptoms of MS. The use of cannabis for recreational purposes is now legal in Canada. However, for many years, people with Multiple Sclerosis (PwMS) have used cannabis either to relax, to reduce pain and spasticity, or to improve sleep and daily functioning. Currently, there is little scientifically established evidence that cannabis works on these symptoms in people with MS. It is therefore important to carry out studies to better understand the efficacy Δ-9-tetrahydrocannabinol (THC), and cannabidiol (CBD) on MS symptoms . THC is known for its analgesic, neuroprotective and anti-inflammatory properties and CBD seems to have positive effects on anxiety and cognitive abilities (memory, concentration).

For this study, investigators hypothesize that administering different doses of THC alone, CBD alone, and THC and CBD combined will result in a significant beneficial effect on spasticity relief compared to placebo.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Cannabis oil vs placebo

Detailed Description

The aim of this study is to document,

1. The efficacy of THC and CBD, alone and in combination, as add-on therapies to the current standard treatments for relief of spasticity and other symptoms in PwMS (muscle spasms and stiffness);
2. Assess the tolerability profile of THC and CBD, alone and in combination, when used in PwMS;
3. Identify the mechanisms underlying such therapeutic and adverse effects of different types of cannabis-based medicines in PwMS,

Participants will initially receive THC 4mg/day or CBD 40mg/day or THC/CBD combination (THC 4mg and CBD 40mg/day), or placebo, on the first day. Dose will be increased up to 20mg (THC) and 200mg (CBD) per day, if well tolerated. Participants will receive the allocated treatment for a total of 4 weeks, followed by an additional 12 weeks of treatment for responders who will be identified as patients who had a decrease from baseline in spasticity of at least one point on the Numerical Rating Scale . THC and CBD will be taken as oil softgels in two divided doses per day. Cannabis extract and placebo will taste and look exactly the same.

To protect from all contingencies and to minimize the risk of adverse reactions, the presence of adverse events will be evaluated at each research visit, as well as through courtesy calls between visits. If any mental or physical symptoms occur that require medical attention, the PwMS will be referred as required to an attending neurologist, psychiatrist, or other specialists .

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pierre Duquette; Phone Number: 0831 514 890 8000; Email: pierre.duquette.med@ssss.gouv.qc.ca
• Study Contact Backup: Name: Amel Zertal; Phone Number: 30883 514 890 8000; Email: amel.zertal.chum@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Recruiting
      • CRCHUM
      • Contact: Amel, Zertal (Project Manager); Phone Number: 30883 15148908000; Email: amel.zertal.chum@ssss.gouv.qc.ca
      • Contact: Dr Pierre, Duquette (PI); Phone Number: 0831 15148908000; Email: pierre.duquette.med@ssss.gouv.qc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants must meet the following criteria:

1. Diagnosed with MS (any subtype), for at least six months, by a MS neurologist, according to the recent version of the McDonald criteria;
2. Spasticity due to MS of at least one-month duration and not relieved with current therapy, at a level of 4 or more on the numerical rating scale (NRS);
3. Stable dose of standard therapies for at least 30 days prior to the screening visit and willingness for these to be maintained for the duration of the study;
4. Aged 21 years or older;
5. Ability (in the investigator's opinion) and willingness to comply with all study requirements;
6. Ability to speak and read French or English (grade-nine level of language required);

Exclusion Criteria:

Participants will be excluded if any of the following criteria are met:

1. Concomitant disease with symptoms of spasticity, or that may have influenced their level;
2. Received a botulinum toxin injection within four months prior to the screening visit or unwillingness to stop receiving botulinum toxin injections for the duration of the study;
3. Use of cannabis or cannabinoid-based medications within 7 days of study entry and unwillingness to abstain for the duration of the study;
4. History of schizophrenia, other psychotic illness or other significant psychiatric disorder other than anxiety or depression associated with their underlying condition;
5. Alcohol or substance use disorder other than nicotine;
6. History of epilepsy or recurrent seizures;
7. Hypersensitivity to cannabinoids or any of the excipients of the study medication;
8. Clinically relevant cardiac dysfunction within the last 12 months or had a cardiac disorder that, in the opinion of the investigator would put the subject at risk of a clinically relevant arrhythmia or myocardial infarction;
9. Impaired renal function i.e., serum creatinine clearance lower than 50 ml/min;
10. Significantly impaired hepatic function, at visit 1, in the investigator's opinion and/or had liver function tests of equal to or greater than three times the upper limit of normal;
11. Pregnancy or breastfeeding;
12. Men with history of fertility problems and who plan to conceive at any time in the future;
13. Any participant who plans to conceive either at screening or while enrolled in the study;
14. Inability (or unwillingness) of women of childbearing potential and men to use a medically acceptable form of contraception throughout the study duration;
15. Inability to use a medically acceptable form of contraception throughout the study duration; m) any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, may influence the result of the study, or the subject's ability to participate in the study;
16. Intention to travel internationally, or to donate blood during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CBD alone; Dosage form : Softgel; Dosage & frequency : 40 mg /day of CBD up to 200 mg in two doses a day; Duration : 4 weeks of treatment followed by 12 additional weeks of follow up.	Drug: Cannabis oil vs placebo; Eligibility, Screening and Baseline (T0): Candidates will be seen by both research staff and a neurologist. Full written informed consent will be obtained before completing questionnaires and administering physical and medical evaluations. If eligibility is confirmed, a blood sample will be collected followed by participant randomisation . Follow-up visits: Randomized participants come back after 4 weeks (T1) for the same assessments administered at T0. Only participants who had a decrease in their level of spasticity can continue their participation in the same allocated arm for an additional period of 12 weeks. At the end of the additional period of 12 weeks (T2), another visit is scheduled for a last assessments which are the same as T0 and T1. Throughout study, courtesy calls will be scheduled and standard care for MS will also be offered to ensure participants 'safety and well-being.; Other Names: Randomized Controlled Trial
Experimental: THC alone; Dosage form : Softgel; Dosage & frequency : 4 mg /day of THC up to 20 mg in two doses a day; Duration : 4 weeks of treatment followed by 12 additional weeks of follow up.	Drug: Cannabis oil vs placebo; Eligibility, Screening and Baseline (T0): Candidates will be seen by both research staff and a neurologist. Full written informed consent will be obtained before completing questionnaires and administering physical and medical evaluations. If eligibility is confirmed, a blood sample will be collected followed by participant randomisation . Follow-up visits: Randomized participants come back after 4 weeks (T1) for the same assessments administered at T0. Only participants who had a decrease in their level of spasticity can continue their participation in the same allocated arm for an additional period of 12 weeks. At the end of the additional period of 12 weeks (T2), another visit is scheduled for a last assessments which are the same as T0 and T1. Throughout study, courtesy calls will be scheduled and standard care for MS will also be offered to ensure participants 'safety and well-being.; Other Names: Randomized Controlled Trial
Experimental: THC and CBD combined; Dosage form : Softgel; Dosage & frequency : 40 mg /day of CBD up to 200 mg and 4 mg /day of THC up to 20 mg in two doses a day; Duration : 4 weeks of treatment followed by 12 additional weeks of follow up.	Drug: Cannabis oil vs placebo; Eligibility, Screening and Baseline (T0): Candidates will be seen by both research staff and a neurologist. Full written informed consent will be obtained before completing questionnaires and administering physical and medical evaluations. If eligibility is confirmed, a blood sample will be collected followed by participant randomisation . Follow-up visits: Randomized participants come back after 4 weeks (T1) for the same assessments administered at T0. Only participants who had a decrease in their level of spasticity can continue their participation in the same allocated arm for an additional period of 12 weeks. At the end of the additional period of 12 weeks (T2), another visit is scheduled for a last assessments which are the same as T0 and T1. Throughout study, courtesy calls will be scheduled and standard care for MS will also be offered to ensure participants 'safety and well-being.; Other Names: Randomized Controlled Trial
Placebo Comparator: Placebo; Dosage form : Softgel; Dosage & frequency : caps of placebo twice a day; Duration : 4 weeks of treatment followed by 12 additional weeks of follow up.	Drug: Cannabis oil vs placebo; Eligibility, Screening and Baseline (T0): Candidates will be seen by both research staff and a neurologist. Full written informed consent will be obtained before completing questionnaires and administering physical and medical evaluations. If eligibility is confirmed, a blood sample will be collected followed by participant randomisation . Follow-up visits: Randomized participants come back after 4 weeks (T1) for the same assessments administered at T0. Only participants who had a decrease in their level of spasticity can continue their participation in the same allocated arm for an additional period of 12 weeks. At the end of the additional period of 12 weeks (T2), another visit is scheduled for a last assessments which are the same as T0 and T1. Throughout study, courtesy calls will be scheduled and standard care for MS will also be offered to ensure participants 'safety and well-being.; Other Names: Randomized Controlled Trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spasticity patient reported change assessment	Patient-reported spasticity: a Numerical rating scale - 0 (No pain) to 10 (worst pain)	Change from Baseline Patient reported spasticity at 28 weeks and 16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spasticity change Clinician assessment	Spasticity: Ashworth scale -1 (normal) to 4 (rigid)	Change from Baseline Clinician evaluation spasticity at 28 weeks and 16 weeks
Pain change assessment	Pain: Pain Effects-1 (Not at all) to 4 (extreme)	Change from Baseline pain at 28 weeks and 16 weeks
Mobility Change assessement	Mobility: Timed 25-Foot Walk test	Change from Baseline mobility at 28 weeks and 16 weeks
Fatigue change assessement	Fatigue: Modified Fatigue Impact Scale-0 (never) to 4 (always)	Change from Baseline fatigue at 28 weeks and 16 weeks
Sleep change assessement	Sleep: Pittsburgh Study Quality sleep Index-0 (no difficult) to 3 (severe)	Change from Baseline sleep at 28 weeks and 16 weeks
Drowsiness change assessement	Drowsiness: Epworth Sleepiness scale-0 (no chance) to 3 (High chance)	Change from Baseline Drowsiness at 28 weeks and 16 weeks
Bowel /Bladder dysfunction change assessement	Bowel /Bladder dysfunction: Bowel/Bladder Control Scale-0 (not at all) to 4 (Daily)	Change from Baseline Bowel/Bladder dysfunction at 28 weeks and 16 weeks
Sexual dysfunction change assessement	Sexual dysfunction: Sexual Satisfaction Scale-0 (Extremely Satisfied) to 6 (Extremely Dissatisfied)	Change from Baseline Sexual dysfunction at 28 weeks and 16 weeks
Restless Legs Syndrome change assessement	Restless Legs Syndrome - 4 (V.severe) to 0 (None)	Change from Baseline Restless Legs Syndrome at 28 weeks and 16 weeks
Mental Health disorder change assessement	Mental Health issues: Mental Health inventory-1 (All of the time) to 6 (None of the time)	Change from Baseline Mental Health at 28 weeks and 16 weeks
Anxiety/Depression change assessement	Anxiety/Depression: Hospital Anxiety and Depression-0 to 3 (highest level)	Change from Baseline Anxiety/Depression at 28 weeks and 16 weeks
Cannabis use disorder assesssment	Cannabis use disorder : diagnosis	Cannabis use disorder : assessment at only baseline
Cognition change assessement	Cognition tests	Change from Baseline cognition at 28 weeks and 16 weeks
Quality of life change assessement	Quality of life: Health Status Questionnaire (Higher scores indicate better health)	Change from Baseline Quality of life at 28 weeks and 16 weeks

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: Canadian Institutes of Health Research (CIHR); Multiple Sclerosis Society of Canada
• Investigators: Principal Investigator: Pierre Duquette, MD, Centre hospitalier de l'Université de Montréal (CHUM)

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2022
• Primary Completion (Estimated): April 10, 2025
• Study Completion (Estimated): May 10, 2025

Study Registration Dates

• First Submitted: September 1, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 25, 2021

Study Record Updates

• Last Update Posted (Estimated): December 13, 2024
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 2021-9017; 431518 (Other Grant/Funding Number: Canadian Institutes of Health Research); AA1 (Other Grant/Funding Number: Multiple Sclerosis Society of Canada)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No