Tipepidine in Children With Attention Deficit/Hyperactivity Disorder (AD/HD): a Double-blind, Placebo-controlled Trial

Phase 1

Completed

• Conditions: Attention Deficit Disorder With Hyperactivity Disease; Attention Deficit and Disruptive Behavior Disorders; Hyperkinesis
• Interventions: Drug: Tipepidine Hibenzate; Drug: Placebo

• Registration Number: NCT02305134
• Lead Sponsor: Chiba University

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

Study Timeline

• Study First Submitted: 2014-11-27
• Study First Submitted QC: 2014-12-01
• Study First Posted: 2014-12-02
• Study Start: 2015-06-11
• Status Verified: 2019-03
• Primary Completion: 2019-03
• Study Completion: 2019-03
• Last Update Submitted: 2019-03-17
• Last Update Posted: 2019-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tipepidine Hibenzate	Tipepidine Hibenzate	Tipepidine is taken orally at 30 mg/day (10 mg after breakfast, 10 mg after supper, and 10 mg before bedtime), for 4 weeks.
Placebo	Placebo	Placebo is taken orally after breakfast, after supper, and before for 4 weeks.

Primary Outcome Measures

Name	Time	Method
The ADHD Rating Scale IV Japanese Version (ADHD-RS-IV-J) by physician.	Changes from baseline in ADHD-RS-IV-J at 4-weeks	The ADHD Rating Scale-IV obtains parent ratings regarding the frequency of each ADHD symptom based on DSM-IV criteria. The ADHD Rating Scale-IV is completed independently by the parent and scored by a clinician. The scale consists of 2 subscales: inattention (9 items) and hyperactivity-impulsivity (9 items).

Secondary Outcome Measures

Name	Time	Method
Total scores and subscores (Inattentive subscore, Hyperactive/impulsive subscore) of the ADHD-RS-IV-J by parents.	Changes from baseline in at 4-weeks
Subscores (Inattentive subscore, Hyperactive/impulsive subscore) of the ADHD-RS-IV-J by physician.	Changes from baseline in at 4-weeks
Total scores and subscores (planning subscore, attention subscore, simultaneous subscore, successive subscore) of DN-CAS (Das-Naglieri Cognitive Assessment System) Japanese Version.	Changes from baseline in at 4-weeks	The DN-CAS is an assessment battery designed to evaluate cognitive processing. It was developed to integrate theoretical and applied areas of psychological knowledge using cognitive processing theory and tests designed to measure-Planning, Attention, Simultaneous, and Successive Processing (PASS)-in individuals ages 5-17. This assessment facilitates mental health professionals in the identification of Attention-Deficit/Hyperactivity Disorder, Traumatic Brain Injury, learning disabilities, Mental Retardation, and giftedness.
Scores of CGI-ADHD-S, CGI-ADHD-I	Changes from baseline in at 4-weeks
Biologocal markers (Serum levels of Pro-BDNF, Mature-BDNF, Oxytocin)	Changes from baseline in at 4-weeks

Trial Locations

Locations (1)

Department of Psychiatry, Chiba University School of Medicine; 🇯🇵 Chiba, Chuo-ku, Japan