Tic Disorders, Tourette Syndrome
Conditions
Keywords
Chronic tic disorders, Tourette syndrome
Brief summary
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.
Interventions
DRUGnabiximols
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
DRUGplacebo
analogous to experimental intervention
Sponsors
German Research Foundation
Hannover Medical School
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Tourette Syndrome-Quality of Life Scale (GTS-QoL) | 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) | — |
| Fitness to Drive Test | 13 weeks | Reaction time and choice reaction (RT) |
| YGTSS-TTS | 8 weeks and 1 month after end of treatment (17 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) | — |
| 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) | — |
Other
| Measure | Time frame |
|---|---|
| blood pressure | through study completion, an average of 17 weeks |
| pulse | through study completion, an average of 17 weeks |
| Assessment of serious adverse events (SAEs) | through study completion, an average of 17 weeks |
| Assessment of adverse events (AEs) | through study completion, an average of 17 weeks |
Countries
Germany
Outcome results
None listed