The Role of SAtivex® in Robotic-Rehabilitation

NCT03186664 | Completed

• 1 other identifier: 13/2016
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Spasticity is frequently experienced by people with Multiple Sclerosis (MS), negatively impacting on patient's motor functional outcome, including walking. Currently, none of the available MS disease-modifying medications has been shown to stop or reverse gait disability. Recently the nabiximols has been tested for the treatment of spasticity and walking impairment in MS. Nabiximols (trade name Sativex®) is an oromucosal spray formulation containing 1:1 fixed ratio of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) derived from cloned Cannabis sativa L. plant. The main active substance, THC, acts as a partial agonist at human cannabinoid receptors (CB1 and CB2), and may modulate the effects of excitatory (glutamate-GLU-) and inhibitory (gamma-aminobutyric acid -GABA-) neurotransmitters, leading to muscle relaxation, which in turn is responsible for spasticity improvement. Cannabinoid receptors may modulate both excitatory and inhibitory transmission at central synapses, and have been heavily implicated, in animal models, in multiple forms of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD). Indeed, in a previous study implying transcranial magnetic stimulation (TMS) technique, it has been hypothesized that the activation of cannabinoid receptors by Sativex® could modulate the balance between LTP and LTD like plasticity by changing the state of cortical excitability. In a recently study it has been proposed that Sativex may modulate the cortical excitability changing the activity of inhibitory GABAergic cortico-cortical synapses. Aim of our study is to clarify the role of Sativex coupled to a robotic neurehabilitation training in MS patients in improving the motor outcome, by means of clinical, kinematic, beside some neurophysiological and measures.

Conditions

Rehabilitation

Outcome Measures

Primary Outcomes (2)

• Functional Independence Measure

  Contains 18 items composed of: This is divided 13 motor tasks and 5 cognitive tasks, considered basic activities of daily living)

  eight months

• 10m walking test

  A tool to better define gait parameters, with regards to speed.

  eight months

Study Arms (2)

A: Sativex+Lokomat Training

EXPERIMENTAL

Patients Sativex responders will perform a neurorobotic-assisted gait training (RAGT, each session will last at least 45', 3 times per week, for a total amount of 20 treatment's sessions).

Device: Lokomat training; Drug: Sativex

B: other antispastic+Lokomat Training

ACTIVE COMPARATOR

Patients treated with others antispastic drugs will perform a neurorobotic-assisted gait training (RAGT, each session will last at least 45', 3 times per week, for a total amount of 20 treatment's sessions).

Device: Lokomat training

Interventions

Lokomat training DEVICE

The neurorobotic treatment will be performed by using the Lokomat (Lokomat, Hocoma, Volketswil, Switzerland) device. The work load will be progressively adjusted based on the improvement of motor performances. Training parameters (weight support, etc) will be individually adapted. During the first Lokomat session, support will be set at 50% of the body weight and will be adapted on observation of the gait. The Lokomat motor guidance system will be first set at 100%, corresponding to a passive walk.

Also known as: RAGT

A: Sativex+Lokomat Training; B: other antispastic+Lokomat Training

Sativex DRUG

Patients in treatment with Sativex will receive cannabis-based medicine extract presented in a pump action sublingual spray. Sativex is composed of whole cannabis plant extract, containing THC (27 mg/mL) and CBD (25 mg/mL), in ethanol/propylene glycol (50:50) excipient. Each actuation delivers 100 KL of spray, containing THC 2.7 mg and CBD 2.5 mg. The number and frequency of dosing (sprays) with Sativex will vary from individual to individual and it may take a number of weeks to find the correct dose of Sativex for the individual patient.

Also known as: Nabiximols

A: Sativex+Lokomat Training

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age of 18-65 years,
• diagnosis of definite relapsing-remitting or primary-progressive Multiple Sclerosis, -absence of clinical relapses from no gadolinium enhanced lesions on brain and spinal cord MRI performed at least six months prior to study entry,
• no mood or sleep disorders (Hamilton score of \<17),
• a moderate to severe spasticity in at least two districts of upper and/or lower limbs; -absence of clinical or neuroradiological relapses from at least six months prior to study entry,
• Expanded Disability Status Scale (EDSS) total score between 3.5 and 7.0,
• no history of psychosis,
• no presence of pace-maker, aneurysms clips, neurostimulator or brain/subdural electrodes (safety TMS procedure),
• right handedness,
• central conduction time in upper limbs of \<8 ms;
• no robotic gait traing contraindications.

You may not qualify if:

• History of psychosis,
• presence of pace-maker, aneurysms clips, neurostimulator or brain/subdural electrodes (safety TMS procedure),
• central conduction time in upper limbs of \<8 ms;
• robotic gait traing contraindications.

Sponsors & Collaborators

• IRCCS Centro Neurolesi Bonino Pulejo: lead

Study Sites (1)

IRCCS Centro Neurolesi Bonino-Pulejo"

Messina, Sicily, 98123, Italy

Location

MeSH Terms

Interventions

nabiximols

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: June 7, 2017
• First Posted: June 14, 2017
• Study Start: December 28, 2016
• Primary Completion: December 1, 2017
• Study Completion: June 1, 2018
• Last Updated: July 26, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)