Multiple Sclerosis
Conditions
Keywords
Multiple sclerosis, Cannabinoids, Spasticity, fMRI, TMS
Brief summary
This is a 10-week, randomised, double blind, placebo-controlled, crossover trial to investigate the effect of Cannabis Based Medicine Extract (Sativex) on patterns of brain activation associated with movement in 20 MS patients suffering from lower limb spasticity. Spasticity is a common symptom in Multiple Sclerosis (MS), occurring all over the course of the disease, particularly in the progressive phase.Physiologically, spasticity and hyperreflexia habitually seen in patients with pyramidal syndrome is due to lesions of other descending pathways, such as the cortico reticulospinal pathways, which participate in voluntary movements.It is now known that an endocannabinoid system acts in humans by at least two types of cannabinoids receptors, CB1 and CB2. There is evidence to support the view that the psychoactive ingredient in cannabis, delta 9-tetrahydrocannabinol (delta 9-THC), and cannabinoids in general, can reduce muscle spasticity in people with MS. Aim of the study will be to evaluate the effect of Sativex on: (i) patterns of brain activation associated with movement (fMRI) in MS patients suffering from spasticity; (ii) changes in level of spasticity (H-reflex); (iii) changes in intracortical excitability and on synaptic intracortical network of the motor areas (double shock TMS).
Detailed description
Baseline assessment will be followed by randomisation and dose introduction. Patients will be randomly assigned to two counterbalanced groups starting either with Sativex or with placebo as the first drug. They will be dispensed sufficient study medication for two weeks together with a diary. During the two-week treatment period all the patients will have to be reached the optimal, individualised dosage to subjectively relief spasticity.Patient will return after three weeks and they will undergo the fMRI and neurophysiological evaluations.Then patients will perform a two-week washout period and they will be requested to intake the alternative medicine. After two weeks patients will perform a second fMRI/neurophysiological study. Two weeks later, after a second washout period, a last visit will be performed to conclude the study.
Interventions
DRUGSativex
Sponsors
University of Roma La Sapienza
S. Andrea Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects between 18 and 60 years of age (inclusive) 2. Have definite Multiple Sclerosis as per Poser Criteria 3. Have either relapsing remitting or secondary progressive course 4. Baseline EDSS score from 3.0 to 6.5 (inclusive) 5. Stable disease for at least 30 days prior to study entry 6. Be right-handed with normal right hand function 7. Female patients of child bearing potential and male patients whose partner is of child bearing potential who are willing to ensure that they or their partner use effective contraception during the study and for three months thereafter 8. If female, be neither pregnant nor breast-feeding. Confirmation that the subjects not pregnant must be established by a negative serum hCG pregnancy test at baseline. 9. No cannabinoids use (cannabis, Marinol, Nabilone) for at least three months prior to entry into the study and willing to abstain from any use of cannabis during the study 10. Significant spasticity in at least two muscle groups defined as a score of 2 or more on the Ashworth scale for each muscle group 11. Antispastic/antiepileptic treatments (dosage, frequency and route of administration) stable for at least one month prior the study entry \-
Exclusion criteria
1. Have a primary progressive MS 2. Patients under disease modifying therapies prescribed in the 6 months prior the study entry 3. Patients who have participated in another research study in the past 6 months 4. Changes in antispastic/antiepileptic treatments (dosage, frequency and route of administration) within one month prior the study entry 5. Have a psychiatric disorders or cognitive impairment that preclude safe participation in the study 6. Known history of alcohol or substance abuse 7. Concurrent clinically important immunologic, pulmonary, renal, liver, active thyroid, and/or other major disease other than MS 8. Severe cardiovascular, disorders, such as ischaemic heart disease, arrhythmias, poorly controlled hypertension or severe heart failure 9. Patients suffering from acute or chronic pain 10. History of epilepsy 11. Female patient who is pregnant, lactating or planning pregnancy during the course of the study 12. Scheduled elective surgery or other procedures requiring general anaesthesia during the study 13. Patient who is terminally ill or is inappropriate for placebo medication 14. Systemic corticosteroid therapy within 4 weeks of randomization or exacerbation of MS within 30 days 15. Regular levodopa therapy within 7 days of the study entry 16. Male patient currently receiving sildenafil (Viagra) and unwilling to stop medication for the duration of the study 17. Patients who are currently taking antiarrhythmic medications 18. Known or suspected adverse reaction to cannabinoids 19. Travel outside the Italy planned during the study 20. Donation of blood during the study 21. Contraindications to MRI scans -
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the effect of Sativex on: a)patterns of brain activation associated with movement(fMRI); b) changes in level of spasticity (H-reflex); c)changes in intracortical excitability and on synaptic intracortical network of the motor areas(TMS). | — |
Countries
Italy
Contacts
Primary ContactCarlo Pozzilli, MD
Backup ContactEmanuela Onesti, MD
Outcome results
None listed