Safety and Efficacy on Spasticity Symptoms of a Cannabis Sativa Extract in Motor Neuron Disease
Condition: Motor Neuron Disease; Amyotrophic Lateral Sclerosis (ALS)
MeSH terms: Muscle Spasticity; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      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)
    

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)
    

Intervention name(s): Cannabis Sativa extract Oromucosal spray
Intervention type(s): Drug
Intervention description(s): Comparison between active drug (Cannabis Sativa extract Oromucosal spray, containing THC (27 mg/ml):CBD (25 mg/ml) vs placebo
Other intervention name(s): Sativex
Intervention MeSH terms: Nabiximols
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Motor Neuron Disease; Amyotrophic lateral sclerosis; Cannabinoids; Sativex; Spasticity