AzTrials
AzTrials

Motor Neuron DiseasePhase 2/3CANALSNCT01776970

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

A Phase 2/3 study testing Cannabis Sativa extract Oromucosal spray in people with Motor Neuron Disease and Amyotrophic Lateral Sclerosis (ALS), run by Ospedale San Raffaele at 4 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Cannabis Sativa extract Oromucosal spray
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
4 sitesItaly
Study dates
Jan 2013to Dec 2015
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 14Show fewer
  • 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:
  • Currently established on a regular dose of anti-spasticity therapy, or
  • 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

Who cannot join

  • 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
Show all 19Show fewer
  • 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

Trial locations and contacts

4 sites in 1 country.

Italy4 sites

  • San Raffaele Scientific Institute

    Milan, 20132

  • Fondazione Salvatore Maugeri IRCCS, Istituto Scientifico

    Milan

  • NEuroMuscular Omnicentre (NEMO), Fondazione Serena - H Cà granda

    Milan

  • Universita' Degli Studi Di Padova, Azienda Ospedaliera Di Padova, Neurologic Department;

    Padova

Other trials in Italy

About this study

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

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)

Read the 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)

Being tested
Cannabis Sativa extract Oromucosal spray
Keywords
Motor Neuron Disease, Amyotrophic lateral sclerosis, Cannabinoids, Sativex, Spasticity
Medical subject headings
Motor Neuron Disease, Amyotrophic Lateral Sclerosis, Marijuana Abuse, Muscle Spasticity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cannabis Sativa extract Oromucosal sprayDrug

    Also called Sativex

    Comparison between active drug (Cannabis Sativa extract Oromucosal spray, containing THC (27 mg/ml):CBD (25 mg/ml) vs placebo

Study groups in NCT01776970
Study groupRoleWhat they receive
SativexExperimentalCannabis Sativa extract Oromucosal spray, containing THC (27 mg/ml):CBD (25 mg/ml)
Receives: Drug: Cannabis Sativa extract Oromucosal spray
PlaceboPlacebo comparatorPlacebo oromucosal spray
Receives: Drug: Cannabis Sativa extract Oromucosal spray

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. modified 5 - points modified Ashworth scale (AS).

    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).

    Measured: Week 7 (6 weeks after randomization)

Secondary outcomes (1)

  1. Mean weekly spasticity, spasm frequency and sleep disruption Numeric Rating Scale (NRS) score

    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)

    Measured: Week 7 (6 weeks after randomizazion)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2013 (estimated)
  2. Study startJan 2013
  3. Primary completionDec 2015
  4. Study completionDec 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01776970
Sponsor's protocol ID
CANALS
Acronym
CANALS
Status last verified
Mar 2017
First submitted
24 Jan 2013
Last updated
9 Mar 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Riva N, Mora G, Soraru G, Lunetta C, Ferraro OE, Falzone Y, Leocani L, Fazio R, Comola M, Comi G; CANALS Study Group. Safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2019 Feb;18(2):155-164. doi: 10.1016/S1474-4422(18)30406-X. Epub 2018 Dec 13.

    PubMed 30554828

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Cannabis Sativa extract Oromucosal spray in people with Motor Neuron Disease and Amyotrophic Lateral Sclerosis (ALS), run by Ospedale San Raffaele at 4 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

modified 5 - points modified Ashworth scale (AS). (time frame: Week 7 (6 weeks after randomization)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01776970, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in