CANNAbinoids in the Treatment of TICS (CANNA-TICS) (CANNA-TICS)

A Randomized Multi-centre Double-blind Placebo Controlled Trial to Demonstrate the Efficacy and Safety of Nabiximols in the Treatment of Adults With Chronic Tic Disorders

This is a multicentre, randomized, double-blind, placebo controlled, parallel-group, phase IIIb trial.

Patients (≥18 years) with chronic tic disorders and Tourette syndrome will be recruited.

The objective of the trial is to demonstrate that treatment with the cannabis extract nabiximols is superior to placebo in reducing tics and comorbidities in patients with Tourette syndrome and chronic tic disorders.

Study Overview

• Status: Completed
• Conditions: Tourette Syndrome; Tic Disorders
• Intervention / Treatment: Drug: nabiximols; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany
    • Uniklinik RWTH Aachen, Psychiatry and Psychotherapy
  • Cologne, Germany
    • University Hospital Cologne, Psychiatry and Psychotherapy
  • Freiburg, Germany
    • University of Freiburg, Psychiatry and Psychotherapy
  • Hannover, Germany
    • Hannover Medical School, Clinic of Psychiatry, Socialpsychiatry and Psychotherapy
  • Luebeck, Germany
    • University Hospital Schleswig-Holstein, Institute of Neurogenetics, Department of Pediatric and Adult Movement Disorders and Neuropsychiatrics
  • Munich, Germany
    • LMU Munich, Psychiatry and Psychotherapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Chronic tic disorder or Tourette syndrome according to DSM-5
2. Age ≥18 years
3. Total tic score of the Yale Global Tic Severity Scale (YGTSS-TTS) > 14 for patients with Tourette syndrome or YGTSS-TTS > 10 for patients with chronic motor or vocal tics only (= CTD)
4. Clinical Global Impression-Severity Score (CGI-S) ≥ 4
5. Medication (and stimulation parameters for deep brain stimulation) for tics and comorbidities must be on a stable dose for at least 30 days before entering the study and patient must consent to maintain the stable dose during the study
6. Signed written informed consent and willingness to comply with treatment and follow-up procedures
7. Patients capable of understanding the investigational nature, potential risks and benefits of the clinical trial
8. Prevention of pregnancy:

Women without childbearing potential defined as follows:

• at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy or
• hysterectomy or uterine agenesis or
• ≥ 50 years and in postmenopausal state ≥ 1 year or
• < 50 years and in postmenopausal state ≥ 1 year with urine FSH > 40 IU/l and urine oestrogen < 30 ng/l or a negative oestrogen test or

Women of childbearing potential with a negative urine ß-HCG pregnancy test at screening who agree to meet one of the following criteria from the time of screening, during the study and for a period of three months following the last administration of study medication:

• correct use of contraception methods. The following are acceptable: hormonal contraceptives (combined oral contraceptives, oestrogen-free pills with desogestrel, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release), intrauterine device (IUS)
• true abstinence (periodic abstinence and withdrawal are not acceptable methods of contraception)
• sexual relationship only with female partners and/or sterile male partners or Males who are not surgically sterile and who are sexually active with female partner(s) of childbearing potential must agree to correct use of one of the following contraception methods from the time of screening, during the study and for a period of three months following the last administration of study medication: hormonal contraceptives (combined oral contraceptives, oestrogen-free pills with desogestrel, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release), intrauterine device (IUS)

Exclusion Criteria:

1. Comorbid obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder (ADHD), depression, anxiety disorder when unstable or in need of an initial adjustment for a therapy
2. Ongoing behavioural treatment for tics
3. History of schizophrenia, psychotic, severe personality, or pervasive developmental disorder
4. Patient has a history of suicidal ideation with intent to act or a plan to act in the 12 months preceding the Screening Visit
5. Current clinical diagnosis of substance abuse or dependence and compulsive disorder
6. Secondary tic disorders and other significant neurological disorders that, in the opinion of the investigator, might interfere with the patient's participation in the study, poses added risk for the patient, or confounds the assessment of patient safety
7. Severe cardiovascular diseases, hepatitis C, or other severe hepatic and renal disorders by history that, in the opinion of the investigator, might interfere with the patient's participation in the study, poses added risk for the patient, or confounds the assessment of patient safety
8. Any medical condition based on medical history, physical examination, and vital sign measurements that, in the opinion of the Investigator, might interfere with the patient's participation in the study, poses added risk for the patient, or confounds the assessment of patient safety
9. Use of cannabis or cannabinoid-based medicine (CBM) in the 30-day period prior to study entry and/or positive delta-9-tetrahydrocannabinol (THC) urine test
10. Positive urine pregnancy test
11. Pregnancy or lactation period
12. The subject has received any investigational medication or used any investigational device within 30 days prior to the first dose of study medication or is actively participating in any investigational drug or device study, or is scheduled to receive an investigational drug or to use an investigational device during the course of the study.
13. Known or suspected hypersensitivity to any of the active substances or any excipients of the investigational medicinal product

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nabiximols, oromucosal spray; 1-12 puffs nabiximols / day, Duration of treatment: 13 weeks	Drug: nabiximols; starting dose (1 puff): 2.7 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD), maximum dose (12 puffs): 32.4 mg THC/30 mg CBD, no target dose is defined Duration of treatment: 13 weeks
Placebo Comparator: placebo, oromucosal spray; 1-12 puffs placebo / day, Duration of treatment: 13 weeks	Drug: placebo; analogous to experimental intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response-rate to treatment according to YGTSS-TTS (Total Tic-Score of the Yale Global Tic Severity Scale [YGTSS])	13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fitness to Drive Test	Reaction time and choice reaction (RT)	13 weeks
Fitness to Drive Test	Stress Behavior capacity (DT-Auslastung)	13 weeks
Fitness to Drive Test	Stress Behavior performance quantity (DT Mengenleistung)	13 weeks
Fitness to Drive Test	Concentration (COG)	13 weeks
Fitness to Drive Test	Perceptual speed (ATAVT)	13 weeks
YGTSS-TTS		8 weeks and 1 month after end of treatment (17 weeks)
YGTSS-TTS		Baseline and 13 weeks
YGTSS-Global Score (YGTSS-GS)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Modified Rush Video-Based Tic Rating Scale (MRVS)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Clinical Global Impression-Improvement Score (CGI-I)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Clinical Global Impression-Severity Score (CGI-S)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Adult Tic Questionnaire (ATQ)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Tourette Syndrome-Quality of Life Scale (GTS-QoL)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Pre-monitory Urge for Tics Scale (PUTS)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Beck Depression Inventory-II (BDI-II)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Conners' Adult ADHD Rating Scale (CAARS)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Beck Anxiety Inventory (BAI)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Pittsburgh Sleep Quality Index (PSQI)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Skala Impulsives-Verhalten-8 (I-8)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
12-item short-form Health Survey (SF-12)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Rage Attacks Questionnaire for Adults with GTS (RAQ-GTS)		8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)

Other Outcome Measures

Outcome Measure	Time Frame
Assessment of adverse events (AEs)	through study completion, an average of 17 weeks
Assessment of serious adverse events (SAEs)	through study completion, an average of 17 weeks
blood pressure	through study completion, an average of 17 weeks
pulse	through study completion, an average of 17 weeks

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Collaborators: German Research Foundation
• Investigators: Principal Investigator: Kirsten Müller-Vahl, MD, Hannover Medical School, Clinic of Psychiatry, Socialpsychiatry and Psychotherapy

Publications and helpful links

General Publications

• Szejko N, Saramak K, Lombroso A, Muller-Vahl K. Cannabis-based medicine in treatment of patients with Gilles de la Tourette syndrome. Neurol Neurochir Pol. 2022;56(1):28-38. doi: 10.5603/PJNNS.a2021.0081. Epub 2021 Oct 28.
• Jakubovski E, Pisarenko A, Fremer C, Haas M, May M, Schumacher C, Schindler C, Häckl S, Aguirre Davila L, Koch A, Brunnauer A, Cimpianu CL, Lutz B, Bindila L, Müller-Vahl K. 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. Front Psychiatry. 2020 Nov 26;11:575826. doi: 10.3389/fpsyt.2020.575826. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2018
• Primary Completion (Actual): November 20, 2020
• Study Completion (Actual): November 20, 2020

Study Registration Dates

• First Submitted: March 6, 2017
• First Submitted That Met QC Criteria: March 16, 2017
• First Posted (Actual): March 22, 2017

Study Record Updates

• Last Update Posted (Actual): December 10, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Tourette syndrome; Chronic tic disorders
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Tourette Syndrome; Tic Disorders; Tics; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Nabiximols
• Other Study ID Numbers: CANNA-TICS; 2016-000564-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No