Use of Cannabinoids in Patients With Multiple Sclerosis

NCT ID: NCT00202423

Last Updated: 2005-11-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-07-31

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.

Conditions

Multiple Sclerosis

Keywords

Multiple sclerosis; Cannabinoids; Spasticity; fMRI; TMS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

Sativex

Intervention Type: DRUG

Eligibility Criteria

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

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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 -

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Roma La Sapienza

OTHER

Sponsor Role: collaborator

S. Andrea Hospital

OTHER

Sponsor Role: lead

Principal Investigators

Maurizio Inghilleri, MD

Role: PRINCIPAL_INVESTIGATOR

Policlinico Umberto I, University of Rome "La Sapienza"

Carlo Pozzilli, MD

Role: STUDY_DIRECTOR

Policlinico Umberto I, University of Rome "La Sapienza"

Locations

Department of Neurology- University of Rome la Sapienza

Rome, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Carlo Pozzilli, MD

Role: CONTACT

Phone: +390649914716

Email: carlo.pozzilli@uniroma1.it

Emanuela Onesti, MD

Role: CONTACT

Phone: +390649914716

Email: emanuela.onesti@uniroma1.it

References

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.

Reference Type: BACKGROUND

PMID: 11060760 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 12137404 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14615106 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10716447 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12617376 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15327042 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15327040 (View on PubMed)

Other Identifiers

CRI.FS032

Identifier Type: -

Identifier Source: secondary_id

NEU-CAN-04

Identifier Type: -

Identifier Source: org_study_id