MUltiple Sclerosis and Extract of Cannabis (MUSEC) Study

Study Overview
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Brief Summary
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Study Objectives: To determine the efficacy and safety of a standardised extract of Cannabis sativa given orally 2 times daily as compared to placebo for the relief of muscle stiffness and pain in multiple sclerosis for a period of 12 weeks. Study Patients: 400 patients with multiple sclerosis (age 18-64, stable disease during previous 6 months, ambulatory or not, antispasticity medication and physiotherapy stabilised ≥ 30 days) with experiencing muscle stiffness ≥ 4 on a 11-point numerical Likert scale at baseline. Study treatment: Group 1: Cannabis extract (delta-9-THC 2.5mg, CBD 1.25 mg per capsule), flexible dosing between 5 mg and 25 mg THC/d, administered twice daily, additionally to previous antispasticity and analgesic medication. Group 2: Matched placebo, twice daily, additionally to previous antispasticity and analgesic medication. Treatment Schedule: Start dose 5 mg THC/d, individual dose titration with increase of 5 mg THC every 3 days, maximal total daily dose 25 mg THC, administered as 2 equal doses based on tolerability. Treatment duration: 12 weeks. Study sites: 20 neurological clinics in the United Kingdom.

Official Title
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Randomised, Double-blind, Placebo-controlled Phase III Trial to Determine the Efficacy and Safety of a Standardised Oral Extract of Cannabis Sativa for the Symptomatic Relief of Muscle Stiffness and Pain in Multiple Sclerosis.

Conditions
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Muscle Spasticity

Intervention / Treatment
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* Drug: standardized cannabis extract
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent. Diagnosis of MS according to McDonald criteria. Current muscle stiffness ≥ 4 on a 11-point categorical rating scale. On-going troublesome muscle stiffness for at least 3 months. Stable disease for the previous 6 months. Antispasticity medication and physiotherapy stabilised for the last 30 days. Patients may be ambulatory or not. Age 18-64. Exclusion Criteria: Immunosuppressants which may affect spasticity (including corticosteroids and interferon but ex-cluding azathioprine) taken currently or in previous 30 days Past or present history of psychotic illness. Open/infected pressure sores or other source of chronic infection. Significant fixed tendon contractures. Severe cognitive impairment such that the patient is unable to provide informed consent. History of clinically important renal, cardiovascular or neurol. diseases (apart from MS). Malignancy within the past 2 years. Cannabinoids taken currently or in previous 30 days. Positive qualitative urinary test on cannabinoids at screening visit. (In this case a patient will be allowed to repeat the test at a second screening visit later.) Known hypersensitivity to cannabinoids. Current drug abuse, including alcohol abuse. Laboratory parameters outside the following limits: Creatinine > 3x upper limit of normal Bilirubine > 3x upper limit of normal Transaminases > 5 x upper limit of normal Anticipated immunisations within the 12 weeks of trial participation. Other problems likely to make participation difficult at the discretion of the neurologist. Women who are pregnant, lactating or not using adequate contraception. Participation in other treatment studies currently or within the previous month.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Cannabis extract (delta-9-THC 2.5mg, CBD 1.25 mg per capsule), flexible dosing between 5 mg and 25 mg THC/d, administered twice daily | Drug: standardized cannabis extract<br>* Cannabis extract (delta-9-THC 2.5mg, CBD 1.25 mg per capsule), flexible dosing between 5 mg and 25 mg THC/d, administered twice daily<br>|
| Placebo Comparator: 2<br>matching placebo capsules, twice daily | Drug: Placebo<br>* Matching placebo capsules, twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle stiffness: 11-point numerical Likert scale |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain: 11-point numerical Likert scale |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple sclerosis, muscle stiffness, spasticity, pain, treatment, cannabinoids