Neurophysiological Study of Sativex in Multiple Sclerosis (MS) Spasticity

Phase 3

Completed

• Conditions: Multiple Sclerosis
• Interventions: Drug: Sativex®; Drug: Placebo

• Registration Number: NCT01538225
• Lead Sponsor: Almirall, S.A.

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-02-20
• Study First Submitted QC: 2012-02-23
• Study First Posted: 2012-02-24
• Study Start: 2012-04
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-17
• Last Update Posted: 2014-01-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
first sativex, second placebo	Sativex®	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)
first sativex, second placebo	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)
first placebo, second sativex	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)
first placebo, second sativex	Placebo	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)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Adverse Events recording	week 0, 4, 6 and 10
Neurophysiology ·H/M ratio ·Transcranial Magnetic Stimulation a) MEP Motor threshold, upper limb b) MEPs amplitudes c) Intracortical facilitation/inhibition (ICI/ICF), upper limb	week 0, 4, 6 and 10	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 Stimulation; 1. Motor threshold to obtain MEPs to the upper limb (time 0-4; 6-10 weeks); 2. 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); 3. Intracortical facilitation/inhibition (ICI/ICF) to the upper limb (time 0-4; 6-10 weeks);
Spasticity: ·0-10 11-point numerical spasticity rating scale (NRS) ·Mean modified Ashworth scale (MAS)	week 0, 4, 6, 10	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
Function: ·Timed 25 feet and 10 meters walk ·Hand dexterity measured with 9-HPT	week 0, 4, 6, 10	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
Other MS Symptoms: ·Sleep Quality NRS ·Pain NRS and Spasm frequency ·Fatigue Severity Scale (FSS)	week 0, 4, 6, 10	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

Trial Locations

Locations (1)

Institute of Experimental Neurology; 🇮🇹 Milan, Italy