Use of Cannabinoids in Patients With Multiple Sclerosis - Full Text View

Sponsors and Collaborators:	S. Andrea Hospital University of Roma La Sapienza
Information provided by:	S. Andrea Hospital
ClinicalTrials.gov Identifier:	NCT00202423

Purpose

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).

Condition	Intervention	Phase
Multiple Sclerosis	Drug: Sativex	Phase II

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Cannabis GW-1000

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	fMRI and Neurophysiological Study Protocol on Cannabinoids in Multiple Sclerosis

Further study details as provided by S. Andrea Hospital:

Primary Outcome Measures:

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).

Estimated Enrollment:	20
Study Start Date:	July 2005

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.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female subjects between 18 and 60 years of age (inclusive)
Have definite Multiple Sclerosis as per Poser Criteria
Have either relapsing remitting or secondary progressive course
Baseline EDSS score from 3.0 to 6.5 (inclusive)
Stable disease for at least 30 days prior to study entry
Be right-handed with normal right hand function
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
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.
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
Significant spasticity in at least two muscle groups defined as a score of 2 or more on the Ashworth scale for each muscle group
Antispastic/antiepileptic treatments (dosage, frequency and route of administration) stable for at least one month prior the study entry

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Exclusion Criteria:

Have a primary progressive MS
Patients under disease modifying therapies prescribed in the 6 months prior the study entry
Patients who have participated in another research study in the past 6 months
Changes in antispastic/antiepileptic treatments (dosage, frequency and route of administration) within one month prior the study entry
Have a psychiatric disorders or cognitive impairment that preclude safe participation in the study
Known history of alcohol or substance abuse
Concurrent clinically important immunologic, pulmonary, renal, liver, active thyroid, and/or other major disease other than MS
Severe cardiovascular, disorders, such as ischaemic heart disease, arrhythmias, poorly controlled hypertension or severe heart failure
Patients suffering from acute or chronic pain
History of epilepsy
Female patient who is pregnant, lactating or planning pregnancy during the course of the study
Scheduled elective surgery or other procedures requiring general anaesthesia during the study
Patient who is terminally ill or is inappropriate for placebo medication
Systemic corticosteroid therapy within 4 weeks of randomization or exacerbation of MS within 30 days
Regular levodopa therapy within 7 days of the study entry
Male patient currently receiving sildenafil (Viagra) and unwilling to stop medication for the duration of the study
Patients who are currently taking antiarrhythmic medications
Known or suspected adverse reaction to cannabinoids
Travel outside the Italy planned during the study
Donation of blood during the study
Contraindications to MRI scans -

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00202423

Contacts

Contact: Carlo Pozzilli, MD	+390649914716	carlo.pozzilli@uniroma1.it
Contact: Emanuela Onesti, MD	+390649914716	emanuela.onesti@uniroma1.it

Locations

Italy
Department of Neurology- University of Rome la Sapienza	Recruiting
Rome, Italy, 00185
Principal Investigator: Maurizio Inghilleri, MD
Sub-Investigator: Carlo Pozzilli, MD
Sub-Investigator: Valentina Tomassini, MD
Sub-Investigator: Emanuela Onesti, MD
Sub-Investigator: Patrizia Pantano, MD

Sponsors and Collaborators

S. Andrea Hospital

University of Roma La Sapienza

Investigators

Principal Investigator:	Maurizio Inghilleri, MD	Policlinico Umberto I, University of Rome "La Sapienza"
Study Director:	Carlo Pozzilli, MD	Policlinico Umberto I, University of Rome "La Sapienza"

More Information

Publications:

Pertwee RG. Cannabinoid receptor ligands: clinical and neuropharmacological considerations, relevant to future drug discovery and development. Expert Opin Investig Drugs. 2000 Jul;9(7):1553-71. Review.

Smith PF. Cannabinoids in the treatment of pain and spasticity in multiple sclerosis. Curr Opin Investig Drugs. 2002 Jun;3(6):859-64. Review.

Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, Thompson A; UK MS Research Group. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet. 2003 Nov 8;362(9395):1517-26.

Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Huffman JW, Layward L. Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature. 2000 Mar 2;404(6773):84-7.

Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003 Feb;17(1):21-9.

Wade DT, Makela P, Robson P, House H, Bateman C. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler. 2004 Aug;10(4):434-41.

Vaney C, Heinzel-Gutenbrunner M, Jobin P, Tschopp F, Gattlen B, Hagen U, Schnelle M, Reif M. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study. Mult Scler. 2004 Aug;10(4):417-24.

Study ID Numbers:	NEU-CAN-04, CRI.FS032
Study First Received:	September 12, 2005
Last Updated:	November 28, 2005
ClinicalTrials.gov Identifier:	NCT00202423
Health Authority:	Italy: Ministry of Health

Keywords provided by S. Andrea Hospital:

Multiple sclerosis
Cannabinoids
Spasticity
fMRI
TMS

Study placed in the following topic categories:

Muscle Spasticity
Autoimmune Diseases
Multiple Sclerosis
Demyelinating Diseases

Demyelinating Autoimmune Diseases, CNS
Demyelinating diseases
Sclerosis
Autoimmune Diseases of the Nervous System

Additional relevant MeSH terms:

Pathologic Processes
Immune System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on January 15, 2009