Pimavanserin Treatment in TS

Study Overview
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Brief Summary
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This research study is determining if a drug called Pimavanserin if safe and effective in the treatment of the symptoms of Tourette Syndrome. Pimavanserin is an investigational drug for Tourette Syndrome, which means it has not been approved by the United States Food and Drug Administration (FDA) to treat Tourette Syndrome. Pimavanserin has been approved by the FDA as a treatment for hallucinations in Parkinson's Disease. It is currently marketed under the name NUPLAZID (pimavanserin) capsules by Acadia Pharmaceuticals.

Detailed Description
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Tourette Syndrome is typically treated with drugs that block or reduce the function of dopamine (a brain chemical involved in movement). However, many of these drugs have adverse effects including irreversible, involuntary movements, typically affecting the face, known as tardive dyskinesia. Newer drugs may have lower risk of tardive dyskinesia. However, many of these drugs are still in clinical trials or are very expensive when used off-label (without FDA approval) to treat Tourette Syndrome. Given these limitations, exploring the potential of other drugs is essential in helping patients. Several studies have shown that serotonin, another chemical in the brain like dopamine, may also play a role in the symptoms of Tourette Syndrome. Serotonin is already the target of many drugs in the treatment of depression, anxiety and obsessive-compulsive disorder which frequently occur in patients with Tourette Syndrome. Pimavanserin is also a drug that works on serotonin system. This means it may be helpful in the treatment of Tourette Syndrome.

Official Title
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An Open Label, Proof-of-Principle, Pilot Study to Evaluate Pimavanserin for the Treatment of Motor and Behavioral Symptoms of Tourette Syndrome

Conditions
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Tourette Syndrome, Tardive Dyskinesia

Intervention / Treatment
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* Drug: Pimavanserin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years of age or older Patients meet the Diagnostic and Statistical Manuel of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for TS and, in the opinion of the investigator and patient, the patient's active tics are causing distress or impairment. Patient has a TTS of 20 or higher on the YGTSS at screening and baseline. Patient can swallow study medical whole. Patient is willing to adhere to the medication regimen and to comply with all study procedures. Patient is in good general health, as indicated by the medical and psychiatric history as well as physical and neurological examination. In the investigator's opinion, the patient has the ability to understand the nature of the study and its procedures, and the patient is expected to complete the study as designed. Patient has provided written informed consent according to local regulations. Females who are postmenarchal or greater than 12 years of age may be included if they have a negative urine pregnancy test at baseline or are sterile. Females who are postmenarchal or great than 12 years of age who male partners are potentially fertile (i.e. no vasectomy) must use highly effective birth control methods for the duration of the study (i.e. starting at screening) and for 30 days or 5 half-lives, whichever is longer after last dose of pimavanserin. The patient must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period and willing to return to the clinic for the follow-up evaluation as specified in this protocol. Exclusion Criteria: Patient has a neurological disorder other than TS that could obscure the evaluation of tics. The patient's predominant movement disorder is stereotypy (coordinated movements that repeat continually and identically) associated with autism spectrum disorder. Patient has a confirmed diagnosis of bipolar disorder, schizophrenia, or another psychotic disorder. Patient has a DSM diagnosis at screening that, in the opinion of the investigator, makes the patient unsuitable for the study. Patient has received Comprehensive Behavioral Intervention for Tics for TS or Cognitive Behavioral Therapy for OCD within 4 weeks of screening. Patient has received treatment with deep brain stimulation, transmagnetic stimulation, or transcranial direct current stimulation within 4 weeks of the screening visit for reduction of tics. Stroke or other uncontrolled serious medical illness such as myocardial infarction within 6 months of baseline. Patient with unknown QT prolongation or in combination with other drugs known to prolong QT interval including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), certain antipsychotics medications (e.g., ziprasidone, chlorpromazine, thioridazine), and certain antibiotics (e.g., gatifloxacin, moxifloxacin). Patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval. Patient has evidence of hepatic impairment. Patient has a known allergy to any of the components of pimavanserin. Patient has participated in an investigational drug or device study and received intervention within 30 days or 5 drug half-lives of baseline, whichever is longer. Patient is a pregnant or lactating female, or plans to be pregnant during the study. Patient has a history of or acknowledges alcohol-related disorder in the previous 12 months, as defined in the DSM-5. Patient has a positive urine drug screen test result or is unable to refrain from substance abuse throughout the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open-label, proof-of-principle, 8-week treatment, pilot study for male and female patients aged 18 years and older with Tourette Syndrome. There were no control groups nor randomization.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pimavanserin<br>All participants will receive pimavanserin 17mg once daily for 1 week and, if the tics are deemed to be inadequately controlled then increase to 34 mg once daily, taken orally as two 17 mg tablets once daily. | Drug: Pimavanserin<br>* Pimavanserin is a serotonin receptor inverse agonist used in treatment of psychosis in Parkinson's disease.<br>* Other names: Nuplazid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effect of pimavanserin on Tourette Syndrome | The primary objective is to evaluate the effect of pimavanserin on motor and phonic tics associated with Tourette Syndrome using the Yale Global Tic Severity Scale. The minimum score for this scale is 0 and the maximum score for this scale 100. A higher score suggests a more sever Tic or that the Tic has a greater impact on the person's life. | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effect of pimavanserin on Tourette Syndrome | A secondary objective is to evaluate the effect of pimavanserin on obsessive-compulsive behaviors associated with Tourette Syndrome using the Yale-Brown Obsessive Compulsive Scale. The minimum score of this scale is 0 and the maximum score of this scale is 40. A higher score represents greater severity of obsessive compulsive symptoms. | 10 weeks | 
| Evaluate the effect of pimavanserin on Tourette Syndrome | A secondary objective is to evaluate the effect of pimavanserin on motor and phonic tics associated with Clinical Global Impression Scale. The minimum score of this scale is 1 and the maximum score of this scale is 7. A higher score suggests a more sever symptom. | 10 weeks | 
| Evaluate the effect of pimavanserin on Tourette Syndrome | A secondary objective is to evaluate the effect of pimavanserin on motor and phonic tics associated with Patient Global Impression of Improvement Scale. The minimum score of this scale is 1 and the maximum score of this scale is 7. A higher score suggests symptoms are very much worse. | 10 weeks | 
| Evaluate the effect of pimavanserin on Tourette Syndrome | A secondary objective is to evaluate the effect of pimavanserin on motor and phonic tics and obsessive-compulsive behaviors associated with Tourette Syndrome using the Columbia-Suicide Severity Rating Scale (C-SSRS). The minimum score of this scale is 2 and the maximum score of this scale is 25, with a higher score indicating more intense ideation and greater risk. | 10 weeks | 
| Evaluate the effect of pimavanserin on Tourette Syndrome | A secondary objective is to evaluate the effect of pimavanserin on motor and phonic tics and obsessive-compulsive behaviors associated with Tourette Syndrome using the Gilles de la Tourette Syndrome Quality of Life Scale. The minimum score is 0 and the maximum score is 108, with a higher score indicating extreme problems. | 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pimavanserin, Tourette Syndrome, tics