Neurophysiological Study of Sativex in Multiple Sclerosis (MS) Spasticity

Multiple Sclerosis Clinical Trial

— NS-MSS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01538225
• Other study ID #: M/SATIVX/01
• Secondary ID: 2011-002258-30
• Status: Completed
• Phase: Phase 3
• First received: February 20, 2012
• Last updated: January 17, 2014
• Start date: April 2012
• Est. completion date: November 2013

Study information

• Verified date: January 2014
• Source: Almirall, S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Muscle Spasticity
• Sclerosis

Intervention

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
• Placebo
Placebo Same frequency and dosage form as Sativex. Duration: 2 weeks

Locations

Country	Name	City	State
Italy	Institute of Experimental Neurology	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Almirall, S.A.

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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 Stimulation; Motor 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	No
Secondary	Adverse Events recording		week 0, 4, 6 and 10	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No