Clinical trial NCT02305134: Tipepidine in Children With Attention Deficit/Hyperactivity Disorder (AD/HD): a Double-blind, Placebo-controlled Trial
Official title: Tipepidine in Children With Attention Deficit/Hyperactivity Disorder (AD/HD): a Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Attention Deficit Disorder With Hyperactivity Disease
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Keywords: Tipepidine, GIRK
Lead sponsor: Chiba University
Sponsor class: OTHER
First posted: 2014-12-02
Enrollment: 21
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Tipepidine (3-\[di-2-thienylmethylene\]-1-methylpiperidine) has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK)-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD) symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this double-blind, placebo-controlled trial is to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD.

Detailed description: Tipepidine (3-\[di-2-thienylmethylene\]-1-methylpiperidine) has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK)-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD) symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this double-blind, placebo-controlled trial is to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD.

See our previous open trial, An Open Study of Tipepidine Hibenzate in Patients With Attention Deficit Hyperactivity Disorder (ADHD) http://clinicaltrials.gov/show/NCT01835093

Eligibility criteria: \[Inclusion Criteria\]

1. Diagnosis of attention deficit hyperactivity disorder besed on DSM-5 criteria.
2. Scores of 20 or higher in ADHD-RS (physician evaluation) total score.
3. currently is an outpatient at Chiba University Hospital Department of Psychiatry or Child Psychiatry.
4. currently receiving no medications for ADHD (atomoxetine, methylphenidate) treatment for the previous 4 weeks prior to enrollment in this study.
5. currently receiving no medications of antidepressants, mood stabilizers and the antipsychotics treatment for the previous 4 weeks prior to enrollment in this study.
6. currently receiving no medications of GIRK channel antagonist (tipepidine, cloperastine, caramiphen) treatment for the previous 4 weeks prior to enrollment in this study.
7. Ages 6 - 17, male or female
8. Provision of written informed consent by patients and parents or guardian.
9. must be able to swallow capsuled medicine.

\[Exclusion Criteria\]

1. History of allergic reaction or hypersensitivity to tipepidine hibenzate.
2. Patients who have not been informed of having the disease at the time of informed consent.
3. Diagnosis of any of the following diseases based on the DSM-5 criteria. Autism Spectrum Disorder, Schizophrenia Spectrum and Other Psychotic Disorders, Neurocognitive Disorders, Substance Related and Addictive Disorders, Feeding and Eating Disorders, Personality Disorders, Paraphilic Disorders.
4. currently receiving medications for ADHD (atomoxetine, methylphenidate) treatment for the previous 4 weeks prior to enrollment in this study.
5. currently receiving medications of antidepressants, mood stabilizers and the antipsychotics treatment for the previous 4 weeks prior to enrollment in this study.
6. currently receiving medications of GIRK channel antagonist (tipepidine, cloperastine, caramiphen) treatment for the previous 4 weeks prior to enrollment in this study.
7. Somatic disorder which requires severe body management or severe meal management.
8. participating in another clinical trial within 3 months prior to enrollment into this study. (except for observation study without intervention).
9. planning change of treatment because of unstable neurological manifestations or somatic symptoms.
10. History of suicidal ideation within the past year.
11. pregnant or nursing, or intending to become pregnant or to start breastfeeding during the study.
12. Other clinically significant reasons for exclusion by investigators.

Primary outcomes:
measure: The ADHD Rating Scale IV Japanese Version (ADHD-RS-IV-J) by physician.
timeFrame: Changes from baseline in ADHD-RS-IV-J at 4-weeks
Secondary outcomes:
measure: Subscores (Inattentive subscore, Hyperactive/impulsive subscore) of the ADHD-RS-IV-J by physician.
timeFrame: Changes from baseline in at 4-weeks
measure: Total scores and subscores (Inattentive subscore, Hyperactive/impulsive subscore) of the ADHD-RS-IV-J by parents.
timeFrame: Changes from baseline in at 4-weeks
measure: Total scores and subscores (planning subscore, attention subscore, simultaneous subscore, successive subscore) of DN-CAS (Das-Naglieri Cognitive Assessment System) Japanese Version.
timeFrame: Changes from baseline in at 4-weeks
measure: Scores of CGI-ADHD-S, CGI-ADHD-I
timeFrame: Changes from baseline in at 4-weeks
measure: Biologocal markers (Serum levels of Pro-BDNF, Mature-BDNF, Oxytocin)
timeFrame: Changes from baseline in at 4-weeks
Other outcomes:
Locations:
city: Chiba
country: Japan
facility: Department of Psychiatry, Chiba University School of Medicine
state: Chuo-ku
Study officials:
References: