Author Topic: (ACTRIMS/ECTRIMS) Sativex (THC-CBD oromucosal spray) and MS spasticity  (Read 127 times)

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Offline agate

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Presented at the ACTRIMS/ECTRIMS conference in Boston, September 10-13, 2014:

Quote
Effect of THC-CBD oromucosal spray (Sativex) on measures of spasticity in multiple sclerosis: a double-blind, placebo-controlled, crossover study   

L Leocani1, A Nuara1, E Houdayer1, U Del Carro1, L Straffi1, V Martinelli1, P Rossi1, I Schiavetti2, S Amadio1, MP Sormani2, G Comi1

1San Raffaele Hospital, Institute of Experimental Neurology (INSPE), Milan, Italy, 2University of Genoa, Health Sciences (DISSAL) - Biostatistics Unit, Genoa, Italy
 
Background:

THC-CBD [tetrahydrocannabinol-cannabidiol] oromucosal spray (Sativex) has proven effective in reducing symptoms associated with spasticity in multiple sclerosis. Little is known on the correlates of such effects on objective measures of spasticity (e.g. spinal H reflex) or corticospinal excitability.

Objectives:

To assess clinical-neurophysiological correlates of Sativex on spasticity in MS.

Methods:

Subjects with progressive MS (43, 20 females, EDSS 3.5-6) and clinical evidence of spasticity (modified Ashworth scale -MAS >1) were randomized to a 2-week titration plus 2-week stable dose of either active THC-CBD (Sativex) or placebo formulation, followed by a second cross-over cycle after 2-week washout, in a double-blind fashion.

Clinical-neurophysiological measures were obtained before and at the end of each phase: MAS [Modified Ashworth Scale], spasticity and pain numeric rating scales-NRS, 10-mt walk, fatigue severity scale, bilateral soleus H/M ratio; Motor Evoked Potential amplitude at 120% threshold and 100% stimulator output, and intracortical inhibition/facilitation. Five subjects dropped (2 during real treatment: 1 for dizziness, 1 subjective weakness; 3 on post-real washout: 1 acute pancreatitis, 1 to enter a rehabilitation program, 1 for family reasons), 4 were not analyzed due to positive THC urine testing on washout. The effect of treatment on changes from baseline was tested using paired Student's t; treatment sequence effect was tested using repeated measures ANOVA, after verifying homogeneity of baselines between subgroups and over time.

Results:

A significant treatment effect was found on MAS with higher improvement after real vs placebo (-1.51 ± 2.20 vs 0.16±2.55; p = 0.009); improvement in MAS and in NRS spasticity were significantly correlated (r 0.38, p 0.025). MAS responders (at least 20% improvement) were significantly more frequent during real treatment (41.2%) vs placebo (11.8%; χ2=5.56, p 0.018). Neurophysiological measures did not significantly differ according to treatment and were not significantly correlated cross-sectionally/longitudinally with clinical parameters, except for a trend between percent changes in MAS and in H/M (r 0.34, p 0.051).

Conclusions:

Our findings confirm clinical beneficial effect of THC-CBD on MS spasticity. The lack of corresponding changes on corticospinal excitability and on the monosynaptic component of the stretch reflex point to the relevance of other spinal and supraspinal mechanisms involved in spasticity physiopathology.


Assigned speakers:
Letizia Leocani, San Raffaele Hospital , Milan , IT
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.

Offline agate

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More on this in MedPage Today, September 17, 2014:

Quote

Sativex Helps MS Spasticity in Objective Tests


By John Gever, Managing Editor, MedPage Today

BOSTON -- An objectively measured sign of spasticity in multiple sclerosis (MS) patients was relieved with Sativex, the oromucosal cannabinoid spray, in a small randomized trial reported here.

Mean scores on the modified Ashworth scale, which measures resistance to muscular stretching, for lower limb spasticity improved by 18.2% (SD 33.7%) in patients treated with Sativex for 4 weeks, compared with a 6.7% improvement (SD 26.6%) in patients using a placebo spray (P=0.029 for the between-group difference), according to Letizia Leocani, MD, PhD, of University Hospital San Raffaele in Milan.

Previous studies had shown that Sativex, which combines tetrahydrocannabinol and cannabidiol in equal parts, improved MS patients' self-reported symptoms of spasticity. But a systematic review and practice guideline released earlier this year by the American Academy of Neurology indicated that the product is "probably ineffective" for objective spasticity measures.

Hence, the current study -- presented at the European Committee for Treatment and Research in Multiple Sclerosis, held jointly this year with its North American counterpart -- provides new support for Sativex as a useful treatment for MS spasticity, an important manifestation that contributes to disability.

It randomized 43 patients to a 2-week titration period followed by 2 weeks of treatment at stable doses with either placebo or Sativex. Following a 2-week washout period, patients then crossed over to a second 4-week cycle with the other treatment.

Exclusion criteria were other medical or psychiatric illnesses that might interfere with treatment or symptomatology, contraindications to transcranial magnetic stimulation, or THC urine test results indicating previous cannabis use.

Patients must have had progressive MS for at least 1 year and modified Ashworth scores at screening of greater than 1 in at least one limb.

Mean patient age in the study was 48 (SD 7) and mean score on the Expanded Disability Status Scale was 5.7 (SD 0.9, range 3.5 to 6.5).

In addition to modified Ashworth score, patients were evaluated with timed 10-meter walks and neurophysiological measures including motor evoked potentials, intracortical inhibition/facilitation, and the so-called H/M ratio (maximal Hoffmann reflex versus the maximal motor response of the soleus muscle).

A responder analysis showed that, among those achieving at least 20% improvement in modified Ashworth scores, half of participants showed such responses only when receiving Sativex. The remainder were divided among patients responding to both the active drug and placebo and those who only responded to placebo.

Importantly, however, Sativex did not produce significant improvements on outcomes other than the modified Ashworth score. In addition to the objective measures, these included patient-reported pain, sleep, and fatigue.

Leocani said these results indicated that additional research is needed on "the relevance of other spinal and supraspinal mechanisms involved in the physiopathology of spasticity."

Sativex is not approved in the U.S.; it is available in several European countries for relief of MS spasticity.

The study was sponsored by Almirall. Medication was provided by GW Pharmaceuticals.

Leocani disclosed relevant relationships with AbbVie, Novartis, Genzyme, Merck Serono, and Almirall.

The article can be seen here.
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.