Safety and Efficacy on Spasticity Symptoms of a Cannabis Sativa Extract in Motor Neuron Disease (CANALS)
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)
Motor Neuron Disease
Amyotrophic Lateral Sclerosis (ALS)
Drug: Cannabis Sativa extract Oromucosal spray
|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|
- 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).
- 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)
- 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
|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)|
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
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)
|Contact: Nilo Riva, MD, PhD||+ 39 - 02 -2643 firstname.lastname@example.org|
|Contact: Susan Lam||+ 39 - 02 -2643 email@example.com|
|San Raffaele Scientific Institute||Recruiting|
|Milan, Italy, 20132|
|Contact: Nilo Riva, MD, PhD +39 - 02 2643 5293 firstname.lastname@example.org|
|Contact: Susan Lam +39 - 02 2643 2990 email@example.com|
|Principal Investigator: Giancarlo Comi, MD|
|Sub-Investigator: Mauro Comola, MD|
|Sub-Investigator: Raffaella Fazio, MD|
|Sub-Investigator: Nilo Riva, MD, PhD|
|Fondazione Salvatore Maugeri IRCCS, Istituto Scientifico||Not yet recruiting|
|Contact: Gabriele Mora, MD|
|Principal Investigator: Gabriele Mora, MD|
|NEuroMuscular Omnicentre (NEMO), Fondazione Serena - H Cà granda||Not yet recruiting|
|Contact: Massimo Corbo, MD|
|Principal Investigator: Massimo Corbo, MD|
|Universita' Degli Studi Di Padova, Azienda Ospedaliera Di Padova, Neurologic Department;||Not yet recruiting|
|Contact: Gianni Sorarù, MD|
|Principal Investigator: Gianni Sorarù, MD|
|Principal Investigator:||Giancarlo Comi, MD||San Raffaele Scientific Institute|