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

Primary Purpose

Multiple Sclerosis

Status
Completed
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Sativex®
Placebo
Sponsored by
Almirall, S.A.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Spasticity

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institute of Experimental Neurology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

first sativex, second placebo

first placebo, second sativex

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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);
Adverse Events recording
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
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
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

Full Information

First Posted
February 20, 2012
Last Updated
January 17, 2014
Sponsor
Almirall, S.A.
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1. Study Identification

Unique Protocol Identification Number
NCT01538225
Brief Title
Neurophysiological Study of Sativex in Multiple Sclerosis (MS) Spasticity
Acronym
NS-MSS
Official Title
Neurophysiologic Study on Effects of Sativex® on Spasticity in Progressive Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Almirall, S.A.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Spasticity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
first sativex, second placebo
Arm Type
Experimental
Arm Description
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)
Arm Title
first placebo, second sativex
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Sativex®
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo Same frequency and dosage form as Sativex. Duration: 2 weeks
Primary Outcome Measure Information:
Title
H/M reflex ratio
Description
To evaluate differences in the H/M ratio scores within subjects affected by progressive MS at baseline and week 4.
Time Frame
week 0, 4
Secondary Outcome Measure Information:
Title
Neurophysiology ·H/M ratio ·Transcranial Magnetic Stimulation a) MEP Motor threshold, upper limb b) MEPs amplitudes c) Intracortical facilitation/inhibition (ICI/ICF), upper limb
Description
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);
Time Frame
week 0, 4, 6 and 10
Title
Adverse Events recording
Time Frame
week 0, 4, 6 and 10
Title
Spasticity: ·0-10 11-point numerical spasticity rating scale (NRS) ·Mean modified Ashworth scale (MAS)
Description
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
Time Frame
week 0, 4, 6, 10
Title
Function: ·Timed 25 feet and 10 meters walk ·Hand dexterity measured with 9-HPT
Description
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
Time Frame
week 0, 4, 6, 10
Title
Other MS Symptoms: ·Sleep Quality NRS ·Pain NRS and Spasm frequency ·Fatigue Severity Scale (FSS)
Description
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
Time Frame
week 0, 4, 6, 10

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giancarlo Comi, Prof
Organizational Affiliation
Institute of Experimental Neurology (Milan, Italy)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Experimental Neurology
City
Milan
ZIP/Postal Code
20132
Country
Italy

12. IPD Sharing Statement

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Neurophysiological Study of Sativex in Multiple Sclerosis (MS) Spasticity

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