The CANNA-TICS Study Protocol: A Randomized Multi-Center Double-Blind Placebo Controlled Trial to Demonstrate the Efficacy and Safety of Nabiximols in the Treatment of Adults With Chronic Tic Disorders

Abstract

Background: Gilles de la Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by motor and vocal tics. First-line treatments for tics are antipsychotics and tic-specific behavioral therapies. However, due to a lack of trained therapists and adverse events of antipsychotic medication many patients seek alternative treatment options including cannabis. Based on the favorable results obtained from case studies on different cannabis-based medicines as well as two small randomized controlled trials using delta-9-tetrahydrocannabinol (THC), we hypothesize that the cannabis extract nabiximols can be regarded as a promising new and safe treatment strategy in TS.Objective: To test in a double blind randomized clinical trial, whether treatment with the cannabis extract nabiximols is superior to placebo in patients with chronic tic disorders.Patients and Methods: This is a multicenter, randomized, double-blind, placebo controlled, parallel-group, phase IIIb trial, which aims to enroll 96 adult patients with chronic tic disorders (TS or chronic motor tic disorder) across 6 centers throughout Germany. Patients will be randomized with a 2:1 ratio into a nabiximols and a placebo arm. The primary efficacy endpoint is defined as tic reduction of at least 30% (compared to baseline) according to the Total Tic Score of the Yale Global Tic Severity Scale (YGTSS-TTS) after 13 weeks of treatment. In addition, several secondary endpoints will be assessed including changes in different psychiatric comorbidities, quality of life, driving ability, and safety assessments.Discussion: This will be the first large, controlled study investigating efficacy and safety of a cannabis-based medicine in patients with TS. Based on available data using different cannabis-based medicines, we expect not only a reduction of tics, but also an improvement of psychiatric comorbidities. If the cannabis extract nabiximols is proven to be safe and effective, it will be a valuable alternative treatment option. The results of this study will be of high health-economic relevance, because a substantial number of patients uses cannabis (illegally) as self-medication.Conclusion: The CANNA-TICS trial will clarify whether nabiximols is efficacious and safe in the treatment of patients with chronic tic disorders.Clinical Trial Registration: This trial is registered at clinicaltrialsregister.eu (Eudra-CT 2016-000564-42) and clinicaltrials.gov (NCT03087201).

Tic Reduction in Adult Onset Gilles De La Tourette Syndrome Using as Required Nabiximols Spray

“…We chose Nabiximols because our patient described good effects in self treatment, affirmative results in other case reports, and the combination of THC and CBD being considered to reduce the undesirable effects of THC and allowing to use the CBD specific effects as well [ 5 7 11 12 ].…”

“…Regarding tics and associated disorders a reduction of symptom burden by Cannabis-based medicine has been shown in small studies and case reports, with self treatment appearing to be common. However, because of the sparcity of studies of older and newer Cannabinoids and results of the last and largest study “CANNA-TICS” still pending, until now no high quality evidence based recommendations could be made [ 9 10 11 ].…”

Cannabis-based medicine in treatment of patients with Gilles de la Tourette syndrome

“…Therefore, it can be expected that the results from the CANNA-TICS trial [67] will provide some of this urgently needed additional data on efficacy and safety of CBM in this group of patients. With respect to the safety profile, there is general agreement that CBMs can be considered as safe and well-tolerated drugs when adhering to the strategy of 'start low, go slow' [68].…”

Recent progress on Tourette syndrome

“…A randomized clinical trial to evaluate the safety and efficacy of cannabis in adults with TS was launched in 2018, but it was terminated because the recruitment and enrollment were prolonged (ClinicalTrials.gov Identifier: NCT03247244). A multicenter, randomized, double-blind, placebo-controlled trial of patients with tic disorders is being conducted to investigate the use of the cannabis extract nabiximols for the treatment of tics 115 .…”