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A randomised controlled cross-over double-blind pilot study protocol on THC:CBD oromucosal spray efficacy as an add-on therapy for post-stroke spasticity.
BMJ Open 2017; 7(9):e016843BO

Abstract

INTRODUCTION

Stroke is the most disabling neurological disorder and often causes spasticity. Transmucosal cannabinoids (tetrahydrocannabinol and cannabidiol (THC:CBD), Sativex) is currently available to treat spasticity-associated symptoms in patients with multiple sclerosis. Cannabinoids are being considered useful also in the treatment of pain, nausea and epilepsy, but may bear and increased risk for cardiovascular events. Spasticity is often assessed with subjective and clinical rating scales, which are unable to measure the increased excitability of the monosynaptic reflex, considered the hallmark of spasticity. The neurophysiological assessment of the stretch reflex provides a precise and objective method to measure spasticity. We propose a novel study to understand if Sativex could be useful in reducing spasticity in stroke survivors and investigating tolerability and safety by accurate cardiovascular monitoring.

METHODS AND ANALYSIS

We will recruit 50 patients with spasticity following stroke to take THC:CBD in a double-blind placebo-controlled cross-over study. Spasticity will be assessed with a numeric rating scale for spasticity, the modified Ashworth scale and with the electromyographical recording of the stretch reflex. The cardiovascular risk will be assessed prior to inclusion. Blood pressure, heart rate, number of daily spasms, bladder function, sleep disruption and adverse events will be monitored throughout the study. A mixed-model analysis of variance will be used to compare the stretch reflex amplitude between the time points; semiquantitative measures will be compared using the Mann-Whitney test (THC:CBD vs placebo) and Wilcoxon test (baseline vs treatment).

ETHICS AND DISSEMINATION

The study was registered on the EudraCT database with number 2016-001034-10 and approved by both the Italian Medicines Agency (Agenzia Italiana del Farmaco) and local Ethics Committee 'Comitato Etico Regionale della Liguria'. Data will be made anonymous and uploaded to a open access repository. Results will be disseminated by presentations at national and international conferences and by publication in journals of clinical neuroscience and neurology.

Authors+Show Affiliations

Department of Neuroscience, Ophthalmology, Rehabilitation, Genetics, Maternal and Child Health, University of Genova, Genova, Italy. Department of Neuroscience, Ospedale Policlinico San Martino, Genova, Italy.Department of Neuroscience, Ophthalmology, Rehabilitation, Genetics, Maternal and Child Health, University of Genova, Genova, Italy. Department of Neuroscience, Ospedale Policlinico San Martino, Genova, Italy.Department of Neuroscience, Ophthalmology, Rehabilitation, Genetics, Maternal and Child Health, University of Genova, Genova, Italy. Department of Neuroscience, Ospedale Policlinico San Martino, Genova, Italy.Department of Neuroscience, Ophthalmology, Rehabilitation, Genetics, Maternal and Child Health, University of Genova, Genova, Italy.Department of Internal Medicine, University of Genova, Genova, Italy.Clinical Trial Unit, Ospedale Policlinico San Martino, Genova, Italy.Academic Neurology Unit , A. Fiorini Hospital, Terracina (LT), Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, Rome, Italy.Department of Neurology and Psichiatry, Neurology Unit, Sapienza University of Rome, Rome, Italy.Department of Neuroscience, Ospedale Policlinico San Martino, Genova, Italy.Department of Neuroscience, Ophthalmology, Rehabilitation, Genetics, Maternal and Child Health, University of Genova, Genova, Italy.Department of Neuroscience, Ophthalmology, Rehabilitation, Genetics, Maternal and Child Health, University of Genova, Genova, Italy. Department of Neuroscience, Ospedale Policlinico San Martino, Genova, Italy.Department of Neuroscience, Ophthalmology, Rehabilitation, Genetics, Maternal and Child Health, University of Genova, Genova, Italy. Department of Neuroscience, Ospedale Policlinico San Martino, Genova, Italy.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

28882919

Citation

Marinelli, Lucio, et al. "A Randomised Controlled Cross-over Double-blind Pilot Study Protocol On THC:CBD Oromucosal Spray Efficacy as an Add-on Therapy for Post-stroke Spasticity." BMJ Open, vol. 7, no. 9, 2017, pp. e016843.
Marinelli L, Balestrino M, Mori L, et al. A randomised controlled cross-over double-blind pilot study protocol on THC:CBD oromucosal spray efficacy as an add-on therapy for post-stroke spasticity. BMJ Open. 2017;7(9):e016843.
Marinelli, L., Balestrino, M., Mori, L., Puce, L., Rosa, G. M., Giorello, L., ... Trompetto, C. (2017). A randomised controlled cross-over double-blind pilot study protocol on THC:CBD oromucosal spray efficacy as an add-on therapy for post-stroke spasticity. BMJ Open, 7(9), pp. e016843. doi:10.1136/bmjopen-2017-016843.
Marinelli L, et al. A Randomised Controlled Cross-over Double-blind Pilot Study Protocol On THC:CBD Oromucosal Spray Efficacy as an Add-on Therapy for Post-stroke Spasticity. BMJ Open. 2017 Sep 7;7(9):e016843. PubMed PMID: 28882919.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A randomised controlled cross-over double-blind pilot study protocol on THC:CBD oromucosal spray efficacy as an add-on therapy for post-stroke spasticity. AU - Marinelli,Lucio, AU - Balestrino,Maurizio, AU - Mori,Laura, AU - Puce,Luca, AU - Rosa,Gian Marco, AU - Giorello,Laura, AU - Currà,Antonio, AU - Fattapposta,Francesco, AU - Serrati,Carlo, AU - Gandolfo,Carlo, AU - Abbruzzese,Giovanni, AU - Trompetto,Carlo, Y1 - 2017/09/07/ PY - 2017/9/9/entrez PY - 2017/9/9/pubmed PY - 2018/5/24/medline KW - THC:CBD KW - cannabinoids KW - sativex KW - spasticity KW - stretch reflex KW - stroke SP - e016843 EP - e016843 JF - BMJ open JO - BMJ Open VL - 7 IS - 9 N2 - INTRODUCTION: Stroke is the most disabling neurological disorder and often causes spasticity. Transmucosal cannabinoids (tetrahydrocannabinol and cannabidiol (THC:CBD), Sativex) is currently available to treat spasticity-associated symptoms in patients with multiple sclerosis. Cannabinoids are being considered useful also in the treatment of pain, nausea and epilepsy, but may bear and increased risk for cardiovascular events. Spasticity is often assessed with subjective and clinical rating scales, which are unable to measure the increased excitability of the monosynaptic reflex, considered the hallmark of spasticity. The neurophysiological assessment of the stretch reflex provides a precise and objective method to measure spasticity. We propose a novel study to understand if Sativex could be useful in reducing spasticity in stroke survivors and investigating tolerability and safety by accurate cardiovascular monitoring. METHODS AND ANALYSIS: We will recruit 50 patients with spasticity following stroke to take THC:CBD in a double-blind placebo-controlled cross-over study. Spasticity will be assessed with a numeric rating scale for spasticity, the modified Ashworth scale and with the electromyographical recording of the stretch reflex. The cardiovascular risk will be assessed prior to inclusion. Blood pressure, heart rate, number of daily spasms, bladder function, sleep disruption and adverse events will be monitored throughout the study. A mixed-model analysis of variance will be used to compare the stretch reflex amplitude between the time points; semiquantitative measures will be compared using the Mann-Whitney test (THC:CBD vs placebo) and Wilcoxon test (baseline vs treatment). ETHICS AND DISSEMINATION: The study was registered on the EudraCT database with number 2016-001034-10 and approved by both the Italian Medicines Agency (Agenzia Italiana del Farmaco) and local Ethics Committee 'Comitato Etico Regionale della Liguria'. Data will be made anonymous and uploaded to a open access repository. Results will be disseminated by presentations at national and international conferences and by publication in journals of clinical neuroscience and neurology. SN - 2044-6055 UR - https://www.unboundmedicine.com/medline/citation/28882919/A_randomised_controlled_cross_over_double_blind_pilot_study_protocol_on_THC:CBD_oromucosal_spray_efficacy_as_an_add_on_therapy_for_post_stroke_spasticity_ L2 - http://bmjopen.bmj.com/cgi/pmidlookup?view=long&pmid=28882919 DB - PRIME DP - Unbound Medicine ER -