Cannabis as a Complementary Treatment in Multiple Sclerosis

NCT ID: NCT05092191

Last Updated: 2024-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-10

Study Completion Date

2025-05-10

Brief Summary

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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.

Detailed Description

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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 .

Conditions

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Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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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.

Group Type EXPERIMENTAL

Cannabis oil vs placebo

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Cannabis oil vs placebo

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Cannabis oil vs placebo

Intervention Type DRUG

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.

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.

Group Type PLACEBO_COMPARATOR

Cannabis oil vs placebo

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Randomized Controlled Trial

Eligibility Criteria

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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.
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

Multiple Sclerosis Society of Canada

OTHER

Sponsor Role collaborator

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pierre Duquette, MD

Role: PRINCIPAL_INVESTIGATOR

Centre hospitalier de l'Université de Montréal (CHUM)

Locations

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CRCHUM

Montreal, Quebec, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Pierre Duquette

Role: CONTACT

Phone: 514 890 8000

Email: [email protected]

Amel Zertal

Role: CONTACT

Phone: 514 890 8000

Email: [email protected]

Facility Contacts

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Amel, Zertal (Project Manager)

Role: primary

Dr Pierre, Duquette (PI)

Role: backup

References

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Zertal A, Alami Marrouni K, Arbour N, Jutras-Aswad D, Pomey MP, Rouleau I, Prat A, Larochelle C, Beaulieu P, Chamelian L, Sylvestre MP, Morin D, Ouellette JS, Frejeau N, Duquette P. Efficacy of cannabinoids compared to the current standard treatments on symptom relief in persons with multiple sclerosis (CANSEP trial): study protocol for a randomized clinical trial. Front Neurol. 2024 Jul 24;15:1440678. doi: 10.3389/fneur.2024.1440678. eCollection 2024.

Reference Type DERIVED
PMID: 39114536 (View on PubMed)

Other Identifiers

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431518

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

AA1

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2021-9017

Identifier Type: -

Identifier Source: org_study_id