Randomized double blind placebo controlled trial to demonstrate the efficacy and safety of nabiximols in the treatment of adults with chronic tic disorders

• Applicant: Professorin Dr. Kirsten Müller-Vahl
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
• Term: from 2016 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 276456785

Gilles de la Tourette syndrome (TS) is a common, complex and chronic neuropsychiatric disorder characterized by motor and vocal tics and psychiatric comorbidities such as attention deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), depression, anxiety, and self-injurious behaviour that causes not only significant impairment in quality of life, but also high costs. The therapeutic spectrum is limited, since in Germany, only haloperidol is licensed (but due to severe adverse effects no longer recommended) and well trained psychotherapist for behavioral therapy using habit reversal training are lacking. Therefore, for the treatment of tics antipsychotics are used off-label. However, a substantial number of patients is unsatisfied with these agents due to adverse effects or lack of efficacy and refuses treatment. It is well known that 2/3 of TS patients seek for alternative medicine including illegal cannabis use. Based on the favorable results obtained from our recent two small controlled trials using the cannabinoid delta-9-tetrahydrocannabinol (THC), we hypothesize that cannabinoid-based medications can be regarded as a promising new and safe treatment strategy in TS. To demonstrate that the cannabis extract nabiximols (containing THC and cannabidiol (CBD) at a ratio of 1:1) is superior to placebo in adult TS patients, we perform a randomized double blind placebo controlled clinical trial including 96 patients at 6 large specialized TS clinics. Treatment will be individually titrated until a maximum tolerated dose (up to 12 puffs = 32.4 mg THC + 30 mg CBD) followed by a 9 weeks stable treatment. The effects of nabiximols on both tics and comobidities as well as adverse effects will be assessed during and after treatment. Nabiximols will be provided by GW pharmaceutical Ltd.On April 5, 2018, the first patient was included in this study (first patient in, FPI). Since then, recruitment has proceeded smoothly, and until today 67% of patients (N = 64) have been enrolled. It is expected that the recruitment will be completed by 02/2020. Unfortunately, there were delays (before study start) due to complicated contract negotiations with GW Pharmaceuticals Ltd. and (after FPI) because of inadequate labeling of the investigational medicinal product (IMP) by the company Haupt Pharma Wülfing GmbH. Therefore, an 18-months life time extension of the study has already been approved by the DFG.

• DFG Programme: Clinical Trials