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

This study is currently recruiting participants.
Verified January 2013 by Almirall, S.A.
Sponsor:
Information provided by (Responsible Party):
Almirall, S.A.
ClinicalTrials.gov Identifier:
NCT01538225
First received: February 20, 2012
Last updated: January 24, 2013
Last verified: January 2013
History of Changes
  Purpose

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).


Condition Intervention Phase
Multiple Sclerosis
 Drug: Sativex®
Drug: Placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Neurophysiologic Study on Effects of Sativex® on Spasticity in Progressive Multiple Sclerosis

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Almirall, S.A.:

Primary Outcome Measures:
  • H/M reflex ratio [ Time Frame: week 0, 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 0, 4, 6 and 10 ] [ Designated as safety issue: No ]

    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);

  • Adverse Events recording [ Time Frame: week 0, 4, 6 and 10 ] [ Designated as safety issue: Yes ]
  • Spasticity: ·0-10 11-point numerical spasticity rating scale (NRS) ·Mean modified Ashworth scale (MAS) [ Time Frame: week 0, 4, 6, 10 ] [ Designated as safety issue: No ]

    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 [ Time Frame: week 0, 4, 6, 10 ] [ Designated as safety issue: No ]

    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) [ Time Frame: week 0, 4, 6, 10 ] [ Designated as safety issue: No ]

    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


Estimated Enrollment: 40
Study Start Date: April 2012
Estimated Study Completion Date: April 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01538225

Contacts
Contact: Carles Vila, Dr carlos.vila@almirall.com

Locations
Italy
Institute of Experimental Neurology Recruiting
Milan, Italy, 20132
Principal Investigator: Giancarlo Comi, Prof            
Sponsors and Collaborators
Almirall, S.A.
Investigators
Principal Investigator: Giancarlo Comi, Prof Institute of Experimental Neurology (Milan, Italy)
  More Information

No publications provided

Responsible Party: Almirall, S.A.
ClinicalTrials.gov Identifier: NCT01538225     History of Changes
Other Study ID Numbers: M/SATIVX/01, 2011-002258-30
Study First Received: February 20, 2012
Last Updated: January 24, 2013
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Almirall, S.A.:
Spasticity

Additional relevant MeSH terms:
Multiple Sclerosis
Muscle Spasticity
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
 Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Signs and Symptoms
Pathologic Processes

ClinicalTrials.gov processed this record on May 16, 2013