Trial to Evaluate the Long-term Efficacy of Oral Aripiprazole in the Treatment of Pediatric Participants With Tourette's Disorder
- Registration Number
- NCT03661983
- Brief Summary
To evaluate the long-term efficacy of oral aripiprazole in pediatric participants for the treatment of Tourette's Disorder (TD).
- Detailed Description
This study will evaluate the long-term efficacy of oral aripiprazole in the treatment of pediatric participants with Tourette's Disorder (TD). The trial consists of 3 distinct phases: a pretreatment phase, open-label stabilization phase, and a double-blind randomized withdrawal phase.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 36
- The participant is a male or female child or adolescent, 6 to 17 years of age (inclusive) at the time of signing the informed consent/assent.
- The participant meets current Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) diagnostic criteria for TD, documented at screening and made by an adequately trained clinician, as confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version.
- The participant has a Total Tic Score (TTS) ≥ 20 on the Yale Global Tic Severity Scale (YGTSS) at screening and baseline (Day 1).
- The participant, a caregiver, and the investigator must all agree that the presenting tic symptoms cause impairment in the participant's normal routines, which include academic achievement, occupational functioning, social activities, and/or relationships.
- Females of childbearing potential (all female participants ≥ 12 years of age and all female participants < 12 years of age if menstruation has started) must have a negative pregnancy test and must not be pregnant or lactating.
- Written informed consent must be obtained from the participant or a legally acceptable representative (eg, guardian or caregiver), in accordance with requirements of the trial site's institutional review board (IRB)/independent ethics committee (IEC) and local regulatory requirements, prior to the initiation of any protocol-required procedures. In addition, the participant, as required by the trial center's IRB/IEC, must provide informed assent at screening and as such must be able to understand that he or she can withdraw from the trial at any time.
- Ability, in the opinion of the principal investigator, of the participant and the participant's legally acceptable representative (e.g., guardian) or caregiver(s) to understand the nature of the trial and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, and discontinuation of prohibited concomitant medications, to read and understand the written word in order to complete participant-reported outcomes measures, and to be reliably rated on assessment scales.
- The participant presents with a clinical presentation and/or history that is consistent with another neurologic condition that may have accompanying abnormal movements. These include, but are not limited to, the following: Transient tic disorder; Huntington's disease; Parkinson's disease; Sydenham's chorea; Wilson's disease; Mental retardation; Pervasive developmental disorder; Tardive dyskinesia; Traumatic brain injury; Stroke; Restless legs syndrome.
- The participant has a history of schizophrenia, bipolar disorder, or other psychotic disorder.
- Participants who receive psychostimulants for the treatment of attention-deficit hyperactivity disorder (ADHD) and who have developed and/or had exacerbations of the tic disorder after the initiation of stimulant treatment. (Note that participants with ADHD who are treated with psychostimulants and have not developed new tics or a worsening of their current tics can be included if all other enrollment obligations are met).
- The participant currently has a primary diagnosis that meets DSM-5 criteria for mood disorder.
- The participant has severe obsessive-compulsive disease, as evidenced by a Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) score > 16.
- The participant has taken aripiprazole within 1 month (30 days) of the screening visit.
- The participant has a history of neuroleptic malignant syndrome.
- Participant is a sexually active male or female of childbearing potential (FOCBP) (all female participants ≥ 12 years of age and all female participants < 12 years of age if menstruation has started) who will not agree to practice 2 acceptable methods of birth control or who will not remain abstinent during the trial and for 30 or 90 days following the last dose of Investigational medicinal product (IMP) for females and males, respectively. Abstinence will be permitted if it is confirmed and documented at every trial visit.
- The participant represents a significant risk of committing suicide based on history (suicide attempt in past 1 year).
- The participant has a body weight < 16 kg.
- Participants who have taken neuroleptic or antiparkinson drugs within 14 days prior to baseline.
- Participants requiring cognitive-behavioral therapy (CBT) for TD during the trial period. CBT for other nonexclusionary disorder must remain consistent through the trial.
- The participant has met DSM-5 criteria for any significant psychoactive substance use disorder within the past 3 months.
- A positive drug screen for cocaine, alcohol, or other drugs of abuse (excluding caffeine, nicotine, or prescribed psychostimulants for ADHD). Investigators can choose to repeat a positive drug screen one time during screening period after concurrence from the medical monitor. A second positive test for any drug of abuse would be exclusionary.
- Participant requiring medication not allowed per protocol.
- Use of any cytochrome P450 (CYP)2D6 and CYP3A4 inhibitors or CYP3A4 inducers within 14 days prior to baseline and for the duration of the trial.
- Other nutritional or dietary supplements and nonprescription herbal preparations for TD (eg, cannabinoids, N-acetylcysteine, omega-3 fatty acids, kava extracts, GABA supplements) within 7 days prior to baseline and for the duration of the trial, unless approved in advance by the medical monitor.
- The inability to swallow tablets or tolerate oral medication.
- Participant has participated in a clinical trial involving either study medication or interventional (non-medication) treatment for TD within the last 60 days.
- The following laboratory test results, vital signs and electrocardiogram (ECG) results are exclusionary: Platelets ≤ 75,000/mm^3; Hemoglobin ≤ 9 g/dL; Neutrophils, absolute ≤ 1000/mm^3; Aspartate aminotransferase > 3 × upper limit of normal (ULN) as defined by the central laboratory; Alanine aminotransferase > 3 × ULN as defined by the central laboratory; Creatinine ≥ 2 mg/dL; Diastolic blood pressure > 105 mmHg; Corrected QT interval ≥ 450 msec (males) or ≥ 470 msec (females) using the corrected QT interval for heart rate using Fridericia's formula
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Double Blind Phase: Placebo Placebo Participants who met randomization criteria and randomized to receive aripiprazole matching-placebo tablets, 2 daily, orally, up to 12 weeks in Double-Blind Phase. Open Label Stabilization Phase: Aripiprazole Aripiprazole Participants began treatment with aripiprazole at a 2.0 mg/day dose, with the dose titrated to 5.0 mg/day after 2 days. Subsequent dose adjustments were based on the participant's weight to achieve optimum control of tics up to the maximum recommended doses based on the United States Labeling, up to Week 8 and then continued on the most stabilized dose up to minimum Week 14 or maximum Week 20. Participants who met stabilization criteria were randomized to Double-blind Randomization Phase. Double Blind Phase: Aripiprazole Full Dose Aripiprazole Participants who met stabilization criteria and randomized to receive full dose of aripiprazole i.e. 5 mg or 10 mg for \<50 kg participants,and 10 mg or 20 mg for \>50 kg participants (2 tablets a day), based on stabilized dose in open-label stabilization phase, up to 12 weeks in Double-Blind Phase. Double Blind Phase: Aripiprazole Half Dose Aripiprazole Participants who met stabilization criteria and randomized to receive half dose of aripiprazole i.e. 2 mg or 5 mg for \<50 kg participants, and 5 mg or 10 mg for \>50 kg participants (2 tablets a day), based on stabilized dose in open-label stabilization phase, up to 12 weeks in Double-Blind Phase.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Relapse During the Double-blind Randomized Withdrawal Phase From Randomization up to 12 weeks in Double-blind Randomized Withdrawal Phase Relapse was defined as a loss of ≥ 50% of the improvement experienced during the open-label stabilization phase (i.e., improvement at the last assessment of Yale Global Tic Severity Scale (YGTSS) before randomization) on the Yale Global Tic Severity Scale Total Tic Score (YGTSS TTS). YGTSS provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic symptoms.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (42)
Reliable Clinical Research
🇺🇸Hialeah, Florida, United States
Pediatric and Adolescent Neurodevelopment Associates
🇺🇸Atlanta, Georgia, United States
Alivation
🇺🇸Lincoln, Nebraska, United States
Comprehensive Research Center
🇺🇸Norwich, Connecticut, United States
Quest Pharmaceutical Services - Miami Research Associates
🇺🇸South Miami, Florida, United States
Neurobehavioral Medicine Group
🇺🇸Bloomfield Hills, Michigan, United States
Aspen Clinical Research - Orem
🇺🇸Orem, Utah, United States
Sarkis Clinical
🇺🇸Gainesville, Florida, United States
IPS Research
🇺🇸Oklahoma City, Oklahoma, United States
Advanced Research Center
🇺🇸Anaheim, California, United States
CT Trials - Riverside
🇺🇸Riverside, California, United States
Syrentis Clinical Research
🇺🇸Santa Ana, California, United States
Inova Clinical trials and Research Center
🇺🇸Fayetteville, Georgia, United States
Eastern Research
🇺🇸Hialeah, Florida, United States
Baber Research Group
🇺🇸Naperville, Illinois, United States
Rothman Center for Pediatric Neuropsychiatry
🇺🇸Saint Petersburg, Florida, United States
Finger Lakes Clinical Research
🇺🇸Rochester, New York, United States
The NeuroCognitive Institute
🇺🇸Mount Arlington, New Jersey, United States
New Hope Clinical Research
🇺🇸Charlotte, North Carolina, United States
Mood Disorders Consulting Medicine
🇺🇸New York, New York, United States
Manhattan Behavioral Medicine
🇺🇸New York, New York, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Quest Therapeutics of Avon Lake DBA Haidar Almhana Nieding
🇺🇸Avon Lake, Ohio, United States
North Star Medical Research
🇺🇸Middleburg Heights, Ohio, United States
Charak Center for Health and Wellness
🇺🇸Garfield Heights, Ohio, United States
University Hills Clinical Research
🇺🇸Irving, Texas, United States
Psychiatric Medical Associates
🇺🇸Plano, Texas, United States
University of Virginia School of Medicine
🇺🇸Charlottesville, Virginia, United States
Clinical Research Partners - Richmond
🇺🇸Petersburg, Virginia, United States
Core Clinical Research
🇺🇸Everett, Washington, United States
Palouse Psychiatry & Behavioral Health
🇺🇸Spokane, Washington, United States
Vadaskert Alaptvany A Gyermekek Lelki Egeszsegeert
🇭🇺Budapest, Hungary
Jodha Tishon Inc.
🇨🇦Toronto, Ontario, Canada
Kids Clinic
🇨🇦Ajax, Ontario, Canada
Semmelweis Egyetem - I. sz. Gyermekgyógyászati Klinika
🇭🇺Budapest, Hungary
Triangle Neuropsychiatry
🇺🇸Durham, North Carolina, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
ClinMed Research Associates, Inc.
🇺🇸Oklahoma City, Oklahoma, United States
Rivus Wellness and Research Institute
🇺🇸Oklahoma City, Oklahoma, United States
Sooner Clinical Research
🇺🇸Oklahoma City, Oklahoma, United States
BioBehavioral Research of Austin
🇺🇸Austin, Texas, United States
Clinical Trials of Texas
🇺🇸San Antonio, Texas, United States