CANNAbinoids in the Treatment of TICS (CANNA-TICS) (CANNA-TICS)
Primary Purpose
Tourette Syndrome, Tic Disorders
Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
nabiximols
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Tourette Syndrome focused on measuring Chronic tic disorders, Tourette syndrome
Eligibility Criteria
Inclusion Criteria:
- Chronic tic disorder or Tourette syndrome according to DSM-5
- Age ≥18 years
- 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)
- Clinical Global Impression-Severity Score (CGI-S) ≥ 4
- 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
- Signed written informed consent and willingness to comply with treatment and follow-up procedures
- Patients capable of understanding the investigational nature, potential risks and benefits of the clinical trial
- 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:
- 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
- Ongoing behavioural treatment for tics
- History of schizophrenia, psychotic, severe personality, or pervasive developmental disorder
- Patient has a history of suicidal ideation with intent to act or a plan to act in the 12 months preceding the Screening Visit
- Current clinical diagnosis of substance abuse or dependence and compulsive disorder
- 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
- 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
- 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
- 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
- Positive urine pregnancy test
- Pregnancy or lactation period
- 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.
- Known or suspected hypersensitivity to any of the active substances or any excipients of the investigational medicinal product
Sites / Locations
- Uniklinik RWTH Aachen, Psychiatry and Psychotherapy
- University Hospital Cologne, Psychiatry and Psychotherapy
- University of Freiburg, Psychiatry and Psychotherapy
- Hannover Medical School, Clinic of Psychiatry, Socialpsychiatry and Psychotherapy
- University Hospital Schleswig-Holstein, Institute of Neurogenetics, Department of Pediatric and Adult Movement Disorders and Neuropsychiatrics
- LMU Munich, Psychiatry and Psychotherapy
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
nabiximols, oromucosal spray
placebo, oromucosal spray
Arm Description
1-12 puffs nabiximols / day, Duration of treatment: 13 weeks
1-12 puffs placebo / day, Duration of treatment: 13 weeks
Outcomes
Primary Outcome Measures
Response-rate to treatment according to YGTSS-TTS (Total Tic-Score of the Yale Global Tic Severity Scale [YGTSS])
Secondary Outcome Measures
Fitness to Drive Test
Reaction time and choice reaction (RT)
Fitness to Drive Test
Stress Behavior capacity (DT-Auslastung)
Fitness to Drive Test
Stress Behavior performance quantity (DT Mengenleistung)
Fitness to Drive Test
Concentration (COG)
Fitness to Drive Test
Perceptual speed (ATAVT)
YGTSS-TTS
YGTSS-TTS
YGTSS-Global Score (YGTSS-GS)
Modified Rush Video-Based Tic Rating Scale (MRVS)
Clinical Global Impression-Improvement Score (CGI-I)
Clinical Global Impression-Severity Score (CGI-S)
Adult Tic Questionnaire (ATQ)
Tourette Syndrome-Quality of Life Scale (GTS-QoL)
Pre-monitory Urge for Tics Scale (PUTS)
Beck Depression Inventory-II (BDI-II)
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
Conners' Adult ADHD Rating Scale (CAARS)
Beck Anxiety Inventory (BAI)
Pittsburgh Sleep Quality Index (PSQI)
Skala Impulsives-Verhalten-8 (I-8)
12-item short-form Health Survey (SF-12)
Rage Attacks Questionnaire for Adults with GTS (RAQ-GTS)
Full Information
NCT ID
NCT03087201
First Posted
March 6, 2017
Last Updated
December 9, 2020
Sponsor
Hannover Medical School
Collaborators
German Research Foundation
1. Study Identification
Unique Protocol Identification Number
NCT03087201
Brief Title
CANNAbinoids in the Treatment of TICS (CANNA-TICS)
Acronym
CANNA-TICS
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
April 5, 2018 (Actual)
Primary Completion Date
November 20, 2020 (Actual)
Study Completion Date
November 20, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hannover Medical School
Collaborators
German Research Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tourette Syndrome, Tic Disorders
Keywords
Chronic tic disorders, Tourette syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
98 (Actual)
8. Arms, Groups, and Interventions
Arm Title
nabiximols, oromucosal spray
Arm Type
Experimental
Arm Description
1-12 puffs nabiximols / day, Duration of treatment: 13 weeks
Arm Title
placebo, oromucosal spray
Arm Type
Placebo Comparator
Arm Description
1-12 puffs placebo / day, Duration of treatment: 13 weeks
Intervention Type
Drug
Intervention Name(s)
nabiximols
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
analogous to experimental intervention
Primary Outcome Measure Information:
Title
Response-rate to treatment according to YGTSS-TTS (Total Tic-Score of the Yale Global Tic Severity Scale [YGTSS])
Time Frame
13 weeks
Secondary Outcome Measure Information:
Title
Fitness to Drive Test
Description
Reaction time and choice reaction (RT)
Time Frame
13 weeks
Title
Fitness to Drive Test
Description
Stress Behavior capacity (DT-Auslastung)
Time Frame
13 weeks
Title
Fitness to Drive Test
Description
Stress Behavior performance quantity (DT Mengenleistung)
Time Frame
13 weeks
Title
Fitness to Drive Test
Description
Concentration (COG)
Time Frame
13 weeks
Title
Fitness to Drive Test
Description
Perceptual speed (ATAVT)
Time Frame
13 weeks
Title
YGTSS-TTS
Time Frame
8 weeks and 1 month after end of treatment (17 weeks)
Title
YGTSS-TTS
Time Frame
Baseline and 13 weeks
Title
YGTSS-Global Score (YGTSS-GS)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
Modified Rush Video-Based Tic Rating Scale (MRVS)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
Clinical Global Impression-Improvement Score (CGI-I)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
Clinical Global Impression-Severity Score (CGI-S)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
Adult Tic Questionnaire (ATQ)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
Tourette Syndrome-Quality of Life Scale (GTS-QoL)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
Pre-monitory Urge for Tics Scale (PUTS)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
Beck Depression Inventory-II (BDI-II)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
Conners' Adult ADHD Rating Scale (CAARS)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
Beck Anxiety Inventory (BAI)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
Pittsburgh Sleep Quality Index (PSQI)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
Skala Impulsives-Verhalten-8 (I-8)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
12-item short-form Health Survey (SF-12)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Title
Rage Attacks Questionnaire for Adults with GTS (RAQ-GTS)
Time Frame
8 weeks, 13 weeks and 1 month after end of treatment (17 weeks)
Other Pre-specified Outcome Measures:
Title
Assessment of adverse events (AEs)
Time Frame
through study completion, an average of 17 weeks
Title
Assessment of serious adverse events (SAEs)
Time Frame
through study completion, an average of 17 weeks
Title
blood pressure
Time Frame
through study completion, an average of 17 weeks
Title
pulse
Time Frame
through study completion, an average of 17 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Chronic tic disorder or Tourette syndrome according to DSM-5
Age ≥18 years
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)
Clinical Global Impression-Severity Score (CGI-S) ≥ 4
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
Signed written informed consent and willingness to comply with treatment and follow-up procedures
Patients capable of understanding the investigational nature, potential risks and benefits of the clinical trial
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:
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
Ongoing behavioural treatment for tics
History of schizophrenia, psychotic, severe personality, or pervasive developmental disorder
Patient has a history of suicidal ideation with intent to act or a plan to act in the 12 months preceding the Screening Visit
Current clinical diagnosis of substance abuse or dependence and compulsive disorder
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
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
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
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
Positive urine pregnancy test
Pregnancy or lactation period
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.
Known or suspected hypersensitivity to any of the active substances or any excipients of the investigational medicinal product
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kirsten Müller-Vahl, MD
Organizational Affiliation
Hannover Medical School, Clinic of Psychiatry, Socialpsychiatry and Psychotherapy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Uniklinik RWTH Aachen, Psychiatry and Psychotherapy
City
Aachen
Country
Germany
Facility Name
University Hospital Cologne, Psychiatry and Psychotherapy
City
Cologne
Country
Germany
Facility Name
University of Freiburg, Psychiatry and Psychotherapy
City
Freiburg
Country
Germany
Facility Name
Hannover Medical School, Clinic of Psychiatry, Socialpsychiatry and Psychotherapy
City
Hannover
Country
Germany
Facility Name
University Hospital Schleswig-Holstein, Institute of Neurogenetics, Department of Pediatric and Adult Movement Disorders and Neuropsychiatrics
City
Luebeck
Country
Germany
Facility Name
LMU Munich, Psychiatry and Psychotherapy
City
Munich
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34708399
Citation
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.
Results Reference
derived
PubMed Identifier
33324255
Citation
Jakubovski E, Pisarenko A, Fremer C, Haas M, May M, Schumacher C, Schindler C, Hackl S, Aguirre Davila L, Koch A, Brunnauer A, Cimpianu CL, Lutz B, Bindila L, Muller-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.
Results Reference
derived
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CANNAbinoids in the Treatment of TICS (CANNA-TICS)
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