Safety and Efficacy on Spasticity Symptoms of a Cannabis Sativa Extract in Motor Neuron Disease (CANALS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Ospedale San Raffaele
Sponsor:
Collaborators:
Fondazione Salvatore Maugeri
Niguarda Hospital
University of Padova
Information provided by (Responsible Party):
Giancarlo Comi, Ospedale San Raffaele
ClinicalTrials.gov Identifier:
NCT01776970
First received: January 24, 2013
Last updated: NA
Last verified: January 2013
History: No changes posted
  Purpose

The clinical primary hypothesis is that there will be a difference between a Cannabis Sativa extract and placebo in their effect on spasticity in Motor Neuron Disease (MND) patients with signs of involvement of the upper motor neuron (UMN) resulting in disabling spasticity.

Secondary goals of the study are to evidence of improvement in other symptoms (in particular pain), and to show favourable trends on functionality measures. Finally, cannabis based drug safety and tolerability will be studied through vital parameters (including weight and pulmonary function) measurement, and analyzing ALS function rating scale progression slope hopefully, showing a slowing of the functional values decrease, owing to cannabis neuroprotective effects)


Condition Intervention Phase
Motor Neuron Disease
Amyotrophic Lateral Sclerosis (ALS)
Drug: Cannabis Sativa extract Oromucosal spray
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Fase II, Randomized, Double-Blind, Placebo-Controlled, Multicentre Study for the Safety and Efficacy on Spasticity Symptoms of a Cannabis Sativa Extract in Motor Neuron Disease Patients

Resource links provided by NLM:


Further study details as provided by Ospedale San Raffaele:

Primary Outcome Measures:
  • modified 5 - points modified Ashworth scale (AS). [ Time Frame: Week 7 (6 weeks after randomization) ] [ Designated as safety issue: No ]
    Improvement in the modified 5 - points modified Ashworth scale (AS). The variable for analysis will be the change in AS from the baseline (visit 2, Week 2) to the end of treatment (visit 4, Week 7).


Secondary Outcome Measures:
  • Mean weekly spasticity, spasm frequency and sleep disruption Numeric Rating Scale (NRS) score [ Time Frame: Week 7 (6 weeks after randomizazion) ] [ Designated as safety issue: No ]
    Mean weekly spasticity, spasm frequency and sleep disruption NRS score at the end of treatment. The variable for analysis will be the change in mean NRS from the baseline (days 0-7) to the last week of treatment (usually days 42-49). Proportion of subjects completing the study and showing an improvement of 30% or more and 50% or more in NRS from Baseline (Week 1) and end of study (last seven days of treatment)


Other Outcome Measures:
  • Pain NRS score [ Time Frame: Week 7 (6 weeks ater randomization) ] [ Designated as safety issue: No ]
    Pain will be measured with the mean of the last 3 days 0 - 10 daily pain intensity NRS.

  • Appetite increase [ Time Frame: Week 7 (6 weeks after randomization) ] [ Designated as safety issue: No ]
    Weight difference before and at the end of the study.

  • Function (Ten meters walk test, ALS-FRS, Barthel ADL Index) [ Time Frame: Week 7 (6 weeks aftar randomization) ] [ Designated as safety issue: No ]
    The time taken for the 10-metre walk, ALS-FRS and Barthel ADL Index will be analysed using the Visit 2 (week 1)result as baseline.

  • Global Impression of Change [ Time Frame: Week 7 (6 weeks after randomization) ] [ Designated as safety issue: No ]
    Carer Global Impression of Change and ease of transfer Physician Global Impression of Change Subject Global Impression of Change

  • Safety [ Time Frame: Week 4, week 7 ] [ Designated as safety issue: Yes ]
    Adverse events, Vital Signs, Physical Examination , oral examination


Estimated Enrollment: 60
Study Start Date: January 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sativex
Cannabis Sativa extract Oromucosal spray, containing THC (27 mg/ml):CBD (25 mg/ml)
Drug: Cannabis Sativa extract Oromucosal spray
Comparison between active drug (Cannabis Sativa extract Oromucosal spray, containing THC (27 mg/ml):CBD (25 mg/ml) vs placebo
Other Name: Sativex
Placebo Comparator: Placebo
Placebo oromucosal spray

Detailed Description:

CANALS project has as a main objective to analyse the safety profile, tolerability and efficacy of a Cannabis Sativa (Sativex) derivative on patients affected by spasticity due to motor neuron disease.

Muscular rigidity (or spasticity) is a symptom that affects many patients with motor neuron disease, concurring to reduce personal autonomy, patients' quality of life and can potentially cause secondary symptomatology (as pain or secondary muscular retractions). Currently available anti-spasticity drugs are often unsatisfactory and their pharmacological action can cause weakness as a secondary effect. There many arguments supporting the use of cannabinoid derivatives in motor neuron diseases. Cannabinoids receptor is expresses both in the brain and in the spinal cord. In animal models cannabinoids have an anti-spasticity effect. Moreover recent studies on ALS animal models demonstrated a neuroprotective effect of cannabinoids, including the preservation of the motor ability and a survival increase of the treated animals. Recently many clinical trials (some of them performed at the Neurological Division of San Raffaele Hospital) demonstrated cannabinoid efficacy on spasticity in Multiple Sclerosis patients. CAnnabinois would be able to reduce spasticity with no secondary weakness effect on treated patients. The results of these studies led to the drug approval in certain countries and by the European Community for the treatment of spasticity in Multiple Sclerosis.

The aim of this study is to analyze the safety, tolerability and efficacy profile of a Cannabis Sativa (Sativex) derivative on patients affected by spasticity due to motor neuron disease ( Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis). The study will be performed along 7 weeks. During the first week will be asked patients to note down in the clinical diary elements related to their symptomatology. Afterwards patients will be randomized in two groups: drug-treated and placebo treated. The study will be followed by a 6-weeks open-label phase during which all patients will receive the active drug (Phase B)

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Subjects must fulfil ALL of the following criteria:

  • Written informed consent
  • Subject able and willing to comply with all study requirements
  • Affected by ALS, either of definite, probable or possible category according to the El Escorial revised criteria or by primary lateral sclerosis (Pringle's criteria)
  • Affected of spasticity, equal or above 1 in the Ashworth Scale for spasticity in 2 or more muscle groups
  • Who will judge spasticity a relevant cause of movements impairment
  • Subject has spasticity due to MND of at least three months duration, which is not wholly relieved with current anti-spasticity therapy
  • Subject fulfils at least one of the two criteria below. Subject must be either:

    1. Currently established on a regular dose of anti-spasticity therapy, or
    2. Previously tried and failed, or could not tolerate suitable anti-spasticity therapy
  • Stabilization of factors affecting spasticity: any physiotherapy regimen or medication likely to affect spasticity will be optimised before the study and not altered in the 3 weeks before start of treatment
  • Subject is willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable.

Additional inclusion Criteria to be met at baseline

• Subjects have registered spasticity NRS scores via the personal clinical diary over the 6 days (day 2 to day 7) before randomization

Exclusion criteria:

  • Any concomitant disease or disorder that has spasticity-like symptoms or that may influence the subject's level of spasticity
  • Subjects receiving Botulinum Toxin during the preceding 6 months
  • Bedridden and tracheotomised patients
  • Fixed-tendon contractures
  • Severe cognitive impairment
  • Currently using or has used cannabis, cannabinoid-based medications or Acomplia (Rimonabant) within 30 days of study entry and unwilling to abstain for the duration of the study
  • Any history or immediate family history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition
  • Any known or suspected history of a diagnosed dependence disorder, current heavy alcohol consumption, current use of an illicit drug or current non-prescribed use of any prescription drug
  • Subjects with poorly controlled epilepsy or recurrent seizures (Subjects who have had one or more fits in the year prior to Visit 1 will be excluded)
  • Any known or suspected hypersensitivity to cannabinoids or any of the excipients
  • Subject has experienced myocardial infarction or clinically relevant cardiac dysfunction within the last 12 months or has a cardiac disorder that, in the opinion of the investigator would put the subject at risk of a clinically relevant arrhythmia or myocardial infarction
  • Subject has a diastolic blood pressure of <50 mmHg or >105 mmHg (when measured in a sitting position at rest for five minutes) or a postural drop in the systolic blood pressure of greater than 20 mmHg
  • Personal history suggestive of relevant impaired renal or hepatic function
  • Female subjects of child bearing potential, unless willing to ensure that they or their partner use effective contraception during the study and for three months thereafter
  • Female subject who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter
  • Subjects who have received any IMP within the 8 weeks before Visit 1
  • Any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the result of the study, or the subject's ability to participate in the study
  • Unwilling to abstain from donation of blood during the study
  • Patients will be asked not to drive while they will be receiving medication
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01776970

Contacts
Contact: Nilo Riva, MD, PhD + 39 - 02 -2643 5293 riva.nilo@hsr.it
Contact: Susan Lam + 39 - 02 -2643 2990 lam.susan@hsr.it

Locations
Italy
Fondazione Salvatore Maugeri IRCCS, Istituto Scientifico Not yet recruiting
Milan, Italy
Contact: Gabriele Mora, MD         
Principal Investigator: Gabriele Mora, MD         
NEuroMuscular Omnicentre (NEMO), Fondazione Serena - H Cà granda Not yet recruiting
Milan, Italy
Contact: Massimo Corbo, MD         
Principal Investigator: Massimo Corbo, MD         
San Raffaele Scientific Institute Recruiting
Milan, Italy, 20132
Contact: Nilo Riva, MD, PhD    +39 - 02 2643 5293    riva.nilo@hsr.it   
Contact: Susan Lam    +39 - 02 2643 2990    lam.susan@hsr.it   
Principal Investigator: Giancarlo Comi, MD         
Sub-Investigator: Mauro Comola, MD         
Sub-Investigator: Raffaella Fazio, MD         
Sub-Investigator: Nilo Riva, MD, PhD         
Universita' Degli Studi Di Padova, Azienda Ospedaliera Di Padova, Neurologic Department; Not yet recruiting
Padova, Italy
Contact: Gianni Sorarù, MD         
Principal Investigator: Gianni Sorarù, MD         
Sponsors and Collaborators
Ospedale San Raffaele
Fondazione Salvatore Maugeri
Niguarda Hospital
University of Padova
Investigators
Principal Investigator: Giancarlo Comi, MD San Raffaele Scientific Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Giancarlo Comi, Prof, Ospedale San Raffaele
ClinicalTrials.gov Identifier: NCT01776970     History of Changes
Other Study ID Numbers: CANALS
Study First Received: January 24, 2013
Last Updated: January 24, 2013
Health Authority: Italy: Ministry of Health

Keywords provided by Ospedale San Raffaele:
Motor Neuron Disease
Amyotrophic lateral sclerosis
Cannabinoids
Sativex
Spasticity

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Muscle Spasticity
Sclerosis
Central Nervous System Diseases
Metabolic Diseases
Muscle Hypertonia
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurologic Manifestations
Neuromuscular Diseases
Neuromuscular Manifestations
Pathologic Processes
Proteostasis Deficiencies
Signs and Symptoms
Spinal Cord Diseases
TDP-43 Proteinopathies

ClinicalTrials.gov processed this record on October 29, 2014