Multiple Sclerosis
Conditions
Keywords
Spasticity
Brief summary
Aim of this randomized, double-blind, placebo-controlled, cross-over study is to investigate cannabinoid-induced changes in neurophysiological parameters in a group of 40 patients with secondary or primary progressive Multiple Sclerosis (MS).
Interventions
DRUGSativex®
THC:CBD 1:1 ratio oromucosal spray. A titration period is required to reach optimal dose. The number and timing of sprays may vary between patients. Duration: 2 weeks
DRUGPlacebo
Placebo Same frequency and dosage form as Sativex. Duration: 2 weeks
Sponsors
Almirall, S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged 18 years or above * Willing and able to comply with the protocol for the duration of the study * Diagnosis of Secondary-Progressive or Primary-Progressive MS from at least 12 months * Relapse free from at least 3 months before screening visit * Lower limb spasticity * EDSS from \> 3.0 and \< 6.5 * Moderate to severe spasticity due to MS from at least 6 months and with stable drug treatment not able to relieve symptoms as a whole, deserving a specific add-on treatment * Immunomodulatory or immunosuppressant therapies not modified during the study and 6 months before starting the study * Stable doses of anti-spasticity agents from at least 2 months prior to screening visit * Have given written informed consent
Exclusion criteria
* Any concomitant disease that may cause spasticity or that could interfere with subject's spasticity * Botulinum Toxin injection for spasticity in the 4 months prior to screening visit * Any known or suspected history of psychotic illness, alcohol or substance abuse, epilepsy, hypersensitivity to cannabinoids * Significant cardiac, renal or hepatic disease * Female subjects of child bearing potentials and male subjects whose partner is child bearing potential, unless willing to ensure that they or their partner use contraception during the study * Female subjects who is pregnant lactating or planning pregnancy during the course of the study and for three months thereafter * Sativex® SmPC contraindications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| H/M reflex ratio | week 0, 4 | To evaluate differences in the H/M ratio scores within subjects affected by progressive MS at baseline and week 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurophysiology ·H/M ratio ·Transcranial Magnetic Stimulation a) MEP Motor threshold, upper limb b) MEPs amplitudes c) Intracortical facilitation/inhibition (ICI/ICF), upper limb | week 0, 4, 6 and 10 | Neurophysiology * H/M ratio: To evaluate differences in the H/M ratio scores within subjects affected by progressive MS at weeks 6 and 10 * Transcranial Magnetic Stimulation 1. Motor threshold to obtain MEPs to the upper limb (time 0-4; 6-10 weeks); 2. MEPs amplitudes at 15% above motor threshold, measured as MEP/M ratio to APB (abductor pollicis brevis) and abductor of hallucis, in which M is the compound muscle potential in response to peripheral stimulation (time 0-4; 6-10 weeks); 3. Intracortical facilitation/inhibition (ICI/ICF) to the upper limb (time 0-4; 6-10 weeks); |
| Adverse Events recording | week 0, 4, 6 and 10 | — |
| Spasticity: ·0-10 11-point numerical spasticity rating scale (NRS) ·Mean modified Ashworth scale (MAS) | week 0, 4, 6, 10 | Mean spasticity score recorded using a 0-10 11-point numerical spasticity rating scale (NRS) at baseline (pre-treatment) and week 4, 6 and 10 · Mean modified Ashworth (MAS) score at baseline (pre-treatment), week 4, 6, 10 |
| Function: ·Timed 25 feet and 10 meters walk ·Hand dexterity measured with 9-HPT | week 0, 4, 6, 10 | Function: * Mean Timed 25 feet and 10 meters walk recorded at baseline (pre-treatment) and week 4, 6, 10 * Mean Hand dexterity measured with 9-HPT recorded at baseline (pre-treatment) and week 4, 6, 10 |
| Other MS Symptoms: ·Sleep Quality NRS ·Pain NRS and Spasm frequency ·Fatigue Severity Scale (FSS) | week 0, 4, 6, 10 | Other MS Symptoms: * Mean Sleep Quality NRS recorded at baseline (pre-treatment) and week 4, 6, 10 * Pain NRS and Spasm frequency recorded at baseline (pre-treatment) and week 4, 6, 10 * Fatigue measured with the Fatigue Severity Scale (FSS) recorded at baseline (pre-treatment) and week 4, 6, 10 |
Countries
Italy
Outcome results
None listed