A Study to Examine the Efficacy of a Therapeutic THX-110 for Tourette Syndrome
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03651726|
Recruitment Status : Not yet recruiting
First Posted : August 29, 2018
Last Update Posted : August 29, 2018
|Condition or disease||Intervention/treatment||Phase|
|Tourette Syndrome||Drug: THX-110 (dronabinol plus PEA) Drug: Placebo||Phase 2|
THX-110 is an investigational drug and is being developed for the treatment of patients with Tourette syndrome and other conditions. THX-110 consists of an active substance from cannabis (dronabinol, tetrahydrocannabinol, THC) and PEA, a substance that occurs naturally in the human body, in animals and plants.
Dronabinol and similar active substances are already approved in some countries for the treatment of other conditions. In some countries, various cannabis-based medications are currently being used in the treatment of patients with Tourette syndrome, mostly without official approval.
PEA has already been used and well tolerated in numerous clinical trials. The combination of PEA and dronabinol is assumed to show better efficacy compared to treatment with dronabinol alone.
The planned study will evaluate the efficacy of THX-110 in the management of tics and other symptoms in patients with Tourette syndrome. Other objectives are to assess study drug dosage and to identify side effects that may be associated with the study drug.
In the first part of the study, half of the patients will receive THX-110, while the other half will receive a placebo. The treatment phase will last 12 weeks. After completion of the first part, patients can decide if they want to participate in the second part of the study. In this optional second part of the study, all patients will receive THX-110 for 12 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Randomized, double-blind, placebo controlled, proof of concept study, followed by an open uncontrolled treatment phase|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized Double Blind Placebo Controlled Proof of Concept Study to Evaluate Safety, Tolerability and Efficacy of Daily Oral THX-110 in Treating Adults With Tourette Syndrome ("Entourage")|
|Estimated Study Start Date :||August 2018|
|Estimated Primary Completion Date :||November 2019|
|Estimated Study Completion Date :||November 2019|
Experimental: THX-110 (dronabinol plus PEA)
Double-blind phase and extension open label phase:
Dose range of 2.5 mg to 10 mg dronabinol (1 to 4 capsules) plus 800 mg PEA (2 tablets) taken orally once daily; starting dose is 2.5 mg dronabinol plus 800 mg PEA. Up-titration is performed within maximal 3 weeks. The titration phase is followed by a maintenance phase of 9 weeks at stable dose.
Drug: THX-110 (dronabinol plus PEA)
2.5 mg dronabinol capsules and 400 mg PEA tablets
Placebo Comparator: Placebo
Range of 1 to 4 dronabinol placebo capsules plus 2 PEA placebo tablets taken orally once daily; starting dose is 1 dronabinol placebo capsule plus 2 PEA placebo tablets. Up-titration is performed within maximal 3 weeks. The titration phase is followed by a maintenance phase of 9 weeks at stable dose.
Sesame oil pill manufactured to mimic 2.5 mg dronabinol capsules; cellulose pill manufactured to mimic 400 mg PEA tablets
- Change in YGTSS-TTS [ Time Frame: Baseline and week 12 of the double-blind phase ]Absolute change in YGTSS-TTS as a continuous endpoint at week 12 of the double-blind phase (visit 9) compared to baseline.
- Response to treatment according to YGTSS-TTS [ Time Frame: Baseline and week 12 of the double-blind phase ]Key secondary endpoint is the response to treatment according to YGTSS-TTS, defined as a reduction in YGTSS-TTS of at least 20% (compared to baseline) at week 12 of the double-blind phase (visit 9).
- YGTSS-TTS as a binary responder criterion and as a continuous endpoint at week 7 of the double-blind phase [ Time Frame: Baseline and week 7 of the double-blind phase ]
- YGTSS-GS (= YGTSS-TTS + YGTSS-impairment score) [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]
- Modified Rush Video-Based Tic Rating Scale (MRVS) [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]No. of Body Areas (score 0-4), Motor Tic Frequency (tics/min) (score 0-4) Phonic Tic Frequency (score 0-4) Severity of Motor Tics (score 0-4) Severity of Phonic Tics (score 0-4) Total score (0-20) 0=best, 20=worst
- Clinical Global Impression-Improvement Score (CGI-I) [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]The CGI-S score obtained at the baseline (initiation) visit serves as a good basis for making this assessment. Only the following one query is rated on a seven-point scale: "Compared to the patient's condition at admission to the project [prior to medication initiation], this patient's condition is: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment."
- Clinical Global Impression-Severity Score (CGI-S) [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]
The CGI-Severity (CGI-S) asks the clinician one question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients.
This rating is based upon observed and reported symptoms, behavior, and function in the past seven days. Clearly, symptoms and behavior can fluctuate over a week; the score should reflect the average severity level across the seven days.
- Adult Tic Questionnaire (ATQ) [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]The ATQ includes a list of 14 common motor tics and 131 common vocal tics. For each type of tic, participants are asked to indicate its presence during the past week by selecting "yes" or "no." Subsequently, for each tic endorsed, participants indicate its frequency and intensity, both on a 4-point Likert-type scale. For the frequency ratings, scores range from a few times a week or less (1), to constantly, almost all the time during the day (4). For the intensity ratings, participants are asked to check (1) if the specific tic was very mild in intensity in the past week, (2) or higher if the tic was obviously noticeable to others; and 3 or higher if the tic was much more forceful and very noticeable to others during the past week. A separate score of tic severity was calculated by summing the intensity and frequency score, resulting in a score between 2 (minimal frequency and intensity) to 8 (maximum frequency and intensity) for each tic endorsed.
- Tourette Syndrome-Quality of Life Scale (GTS-QoL) [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]
HRQOL is often measured by four core questions that asked about general health status and number of unhealthy days in the Behavioral Risk Factor Surveillance System (BRFSS).
HrQoL in GTS patients is evaluated using the generic EQ-5D instrument (ref: EuroQol-Group. EQ-5D. Available at:www.euroqol.org. 2006.). It includes a five dimension descriptive system and a visual analog scale (EQVAS). The five dimensions include ''Mobility,'' ''Self-Care,'' ''Usual Activities,'' ''Pain/Discomfort,'' and ''Anxiety/Depression.'' All dimensions are subdivided into three levels (no problems, some problems, and extreme problems). Calculation of EQ-5D index score was performed using a regression algorithm generated by Greiner et al (ref: Greiner W, et al. The measurement and valuation of health status using EQ-5D: a European perspective. Dordrecht: Kluwer Academic Publisher; 2003.)
- Pre-monitory Urge for Tics Scale (PUTS) [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]The PUTS is a 9-item self-report questionnaire measuring premonitory sensations in individuals with tics. Each item is scored from 1 (not at all true) to 4 (very much true). The total score is computed by summing the 9 items. Thus, total scores range from 9 to 36, and higher scores represent greater premonitory urges. The PUTS has demonstrated good internal consistency, test-retest reliability, and construct validity among youths between 11 and 16 years of age.The present manuscript reports the first psychometric data on the 9-item PUTS in an older adolescent and adult sample.
- Beck Depression Inventory (BDI) [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]
Add up the score for each of the twenty-one questions. The highest possible total for the whole test would be sixty-three. This would mean the number three was answered on all twenty-one questions. Since the lowest possible score for each question is zero, the lowest possible score for the test would be zero.
Total Score____________________Levels of Depression 1-10____________________These ups and downs are considered normal 11-16___________________ Mild mood disturbance 17-20___________________Borderline clinical depression 21-30___________________Moderate depression 31-40___________________Severe depression over 40__________________Extreme depression
- Yale-Brown Obsessive Compulsive Scale (Y BOCS) [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]The YBOCS is a 10-item clinician-rated measure of OCD symptom severity. Raters assess obsessions and compulsions separately in five domains: time spent, interference, distress, resistance, and control. Each domain is rated on a scale from 0 to 4. Thus, total scores range from 0 to 40, with higher scores indicating greater symptom severity.
- Conners' Adult ADHD Rating Scale (CAARS) [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]The self-report and observer forms contain an identical set of scales, subscales, and indexes with a total of 30 items : Total ADHD symptoms: Inattentive (9 items), Hyperactive-Impulsive (9 items) subscales and ADHD Index (12 items) with each item rated on a 4-point scale (0=never, 1= a little, 2=often, 3= frequently) derived from from Conners' ADHD Rating Scale (CARS).
- Beck Anxiety Inventory (BAI) [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]The total score is calculated by finding the sum of the 21 items. Score of 0-21 = low anxiety Score of 22-35 = moderate anxiety Score of 36 and above = potentially concerning levels of anxiety
- Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]The Pittsburgh Sleep Quality Index (PSQI) contains 19 self-rated questions and 5 questions rated by the bed partner or roommate (if one is available). Only self-rated questions are included in the scoring. The 19 self-rated items are combined to form seven "component" scores, each of which has a range of 0-3 points. In all cases, a score of "0" indicates no difficulty, while a score of "3" indicates severe difficulty. The seven component scores are then added to yield one "global" score, with a range of 0-21 points, "0" indicating no difficulty and "21 " indicating severe difficulties in all areas.
- 12-item short-form (SF-12) Health Survey [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]
The SF-12 is a multipurpose short form survey with 12 questions, all selected from the SF-36 Health Survey. The questions were combined, scored, and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life.
Physical and Mental Health Composite Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
- Rage Attacks Questionnaire (RAQ) [ Time Frame: Baseline, week 7 and week 12 of the double-blind phase, week 19 and week 24 of the extension open label phase ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03651726
|Contact: Kirsten Müller-Vahl, Prof. Dr.||+49 511 532 ext firstname.lastname@example.org|
|Contact: Christoph Schindler, Prof. Dr.||+49 511 5350 ext email@example.com|
|Medizinische Hochschule Hannover, Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie||Not yet recruiting|
|Hannover, Germany, 30625|
|Contact: Kirsten Müller-Vahl, Prof. Dr.|
|LMU Klinikum der Universität München, Klinik für Psychiatrie und Psychotherapie||Not yet recruiting|
|Munich, Germany, 80336|
|Contact: Richard Musil, Dr. med.|
|Study Chair:||Kirsten Müller-Vahl, Prof. Dr.||Medizinische Hochschule Hannover, Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie|