Use of Cannabinoids in Patients With Multiple Sclerosis

NCT00202423 | Unknown Phase 2

• 2 other identifiers: NEU-CAN-04CRI.FS032
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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).

Conditions

Multiple Sclerosis

Keywords

Multiple sclerosis; Cannabinoids; Spasticity; fMRI; TMS

Outcome Measures

Primary Outcomes (1)

• 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).

Interventions

Sativex DRUG

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• S. Andrea Hospital: lead
• University of Roma La Sapienza: collaborator

Study Sites (1)

Department of Neurology- University of Rome la Sapienza

Rome, 00185, Italy

RECRUITING

Related Publications (7)

• 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. doi: 10.1517/13543784.9.7.1553.

  PMID: 11060760 BACKGROUND

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

  PMID: 12137404 BACKGROUND

• 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. doi: 10.1016/S0140-6736(03)14738-1.

  PMID: 14615106 BACKGROUND

• 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. doi: 10.1038/35003583.

  PMID: 10716447 BACKGROUND

• 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. doi: 10.1191/0269215503cr581oa.

  PMID: 12617376 BACKGROUND

• 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. doi: 10.1191/1352458504ms1082oa.

  PMID: 15327042 BACKGROUND

• 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. doi: 10.1191/1352458504ms1048oa.

  PMID: 15327040 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Muscle Spasticity

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Maurizio Inghilleri, MD

  Policlinico Umberto I, University of Rome "La Sapienza"

  PRINCIPAL INVESTIGATOR

• Carlo Pozzilli, MD

  Policlinico Umberto I, University of Rome "La Sapienza"

  STUDY DIRECTOR

Central Study Contacts

Carlo Pozzilli, MD

CONTACT

+390649914716; carlo.pozzilli@uniroma1.it

Emanuela Onesti, MD

CONTACT

+390649914716; emanuela.onesti@uniroma1.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: July 1, 2005
• Last Updated: November 29, 2005

Record last verified: 2005-09

Locations

IT (1)