Neurophysiological Study of Sativex in Multiple Sclerosis (MS) Spasticity (NS-MSS)

Neurophysiologic Study on Effects of Sativex® on Spasticity in Progressive Multiple Sclerosis

Aim of this randomized, double-blind, placebo-controlled, cross-over study is to investigate cannabinoid-induced changes in neurophysiological parameters in a group of 40 patients with secondary or primary progressive Multiple Sclerosis (MS).

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Sativex®; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20132
    • Institute of Experimental Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 years or above
• Willing and able to comply with the protocol for the duration of the study
• Diagnosis of Secondary-Progressive or Primary-Progressive MS from at least 12 months
• Relapse free from at least 3 months before screening visit
• Lower limb spasticity
• EDSS from > 3.0 and < 6.5
• Moderate to severe spasticity due to MS from at least 6 months and with stable drug treatment not able to relieve symptoms as a whole, deserving a specific add-on treatment
• Immunomodulatory or immunosuppressant therapies not modified during the study and 6 months before starting the study
• Stable doses of anti-spasticity agents from at least 2 months prior to screening visit
• Have given written informed consent

Exclusion Criteria:

• Any concomitant disease that may cause spasticity or that could interfere with subject's spasticity
• Botulinum Toxin injection for spasticity in the 4 months prior to screening visit
• Any known or suspected history of psychotic illness, alcohol or substance abuse, epilepsy, hypersensitivity to cannabinoids
• Significant cardiac, renal or hepatic disease
• Female subjects of child bearing potentials and male subjects whose partner is child bearing potential, unless willing to ensure that they or their partner use contraception during the study
• Female subjects who is pregnant lactating or planning pregnancy during the course of the study and for three months thereafter
• Sativex® SmPC contraindications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: first sativex, second placebo; 2 weeks first titration period (as per approved SmPC), a 2-week first treatment period (Sativex), a 2-week washout, a cross-over followed by another 2 weeks titration period (as per SmPC), followed by a second 2-week period treatment (placebo)	Drug: Sativex®; THC:CBD 1:1 ratio oromucosal spray. A titration period is required to reach optimal dose. The number and timing of sprays may vary between patients. Duration: 2 weeks; Drug: Placebo; Placebo Same frequency and dosage form as Sativex. Duration: 2 weeks
Experimental: first placebo, second sativex; 2 weeks first titration period (as per approved SmPC), a 2-week first treatment period (placebo), a 2-week washout, a cross-over followed by another 2 weeks titration period (as per SmPC), followed by a second 2-week period treatment (Sativex)	Drug: Sativex®; THC:CBD 1:1 ratio oromucosal spray. A titration period is required to reach optimal dose. The number and timing of sprays may vary between patients. Duration: 2 weeks; Drug: Placebo; Placebo Same frequency and dosage form as Sativex. Duration: 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
H/M reflex ratio	To evaluate differences in the H/M ratio scores within subjects affected by progressive MS at baseline and week 4.	week 0, 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurophysiology ·H/M ratio ·Transcranial Magnetic Stimulation a) MEP Motor threshold, upper limb b) MEPs amplitudes c) Intracortical facilitation/inhibition (ICI/ICF), upper limb	Neurophysiology; H/M ratio: To evaluate differences in the H/M ratio scores within subjects affected by progressive MS at weeks 6 and 10; Transcranial Magnetic StimulationMotor threshold to obtain MEPs to the upper limb (time 0-4; 6-10 weeks);MEPs amplitudes at 15% above motor threshold, measured as MEP/M ratio to APB (abductor pollicis brevis) and abductor of hallucis, in which M is the compound muscle potential in response to peripheral stimulation (time 0-4; 6-10 weeks);Intracortical facilitation/inhibition (ICI/ICF) to the upper limb (time 0-4; 6-10 weeks);	week 0, 4, 6 and 10
Adverse Events recording		week 0, 4, 6 and 10
Spasticity: ·0-10 11-point numerical spasticity rating scale (NRS) ·Mean modified Ashworth scale (MAS)	Mean spasticity score recorded using a 0-10 11-point numerical spasticity rating scale (NRS) at baseline (pre-treatment) and week 4, 6 and 10 · Mean modified Ashworth (MAS) score at baseline (pre-treatment), week 4, 6, 10	week 0, 4, 6, 10
Function: ·Timed 25 feet and 10 meters walk ·Hand dexterity measured with 9-HPT	Function: Mean Timed 25 feet and 10 meters walk recorded at baseline (pre-treatment) and week 4, 6, 10; Mean Hand dexterity measured with 9-HPT recorded at baseline (pre-treatment) and week 4, 6, 10	week 0, 4, 6, 10
Other MS Symptoms: ·Sleep Quality NRS ·Pain NRS and Spasm frequency ·Fatigue Severity Scale (FSS)	Other MS Symptoms: Mean Sleep Quality NRS recorded at baseline (pre-treatment) and week 4, 6, 10; Pain NRS and Spasm frequency recorded at baseline (pre-treatment) and week 4, 6, 10; Fatigue measured with the Fatigue Severity Scale (FSS) recorded at baseline (pre-treatment) and week 4, 6, 10	week 0, 4, 6, 10

Collaborators and Investigators

• Sponsor: Almirall, S.A.
• Investigators: Principal Investigator: Giancarlo Comi, Prof, Institute of Experimental Neurology (Milan, Italy)

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: February 20, 2012
• First Submitted That Met QC Criteria: February 23, 2012
• First Posted (Estimate): February 24, 2012

Study Record Updates

• Last Update Posted (Estimate): January 20, 2014
• Last Update Submitted That Met QC Criteria: January 17, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Spasticity
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Hypertonia; Multiple Sclerosis; Sclerosis; Muscle Spasticity; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Nabiximols
• Other Study ID Numbers: M/SATIVX/01; 2011-002258-30 (EudraCT Number)