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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

Tipepidine Hibenzate

Placebo

About this trial

This is an interventional treatment trial for Attention Deficit Disorder With Hyperactivity Disease focused on measuring Tipepidine, GIRK

Eligibility Criteria

6 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

[Inclusion Criteria]

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

[Exclusion Criteria]

History of allergic reaction or hypersensitivity to tipepidine hibenzate.
Patients who have not been informed of having the disease at the time of informed consent.
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.
currently receiving medications for ADHD (atomoxetine, methylphenidate) treatment for the previous 4 weeks prior to enrollment in this study.
currently receiving medications of antidepressants, mood stabilizers and the antipsychotics treatment for the previous 4 weeks prior to enrollment in this study.
currently receiving medications of GIRK channel antagonist (tipepidine, cloperastine, caramiphen) treatment for the previous 4 weeks prior to enrollment in this study.
Somatic disorder which requires severe body management or severe meal management.
participating in another clinical trial within 3 months prior to enrollment into this study. (except for observation study without intervention).
planning change of treatment because of unstable neurological manifestations or somatic symptoms.
History of suicidal ideation within the past year.
pregnant or nursing, or intending to become pregnant or to start breastfeeding during the study.
Other clinically significant reasons for exclusion by investigators.

Sites / Locations

Department of Psychiatry, Chiba University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Tipepidine Hibenzate

Placebo

Arm Description

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 is taken orally after breakfast, after supper, and before for 4 weeks.

Outcomes

Primary Outcome Measures

The ADHD Rating Scale IV Japanese Version (ADHD-RS-IV-J) by physician.

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

Subscores (Inattentive subscore, Hyperactive/impulsive subscore) of the ADHD-RS-IV-J by physician.

Total scores and subscores (Inattentive subscore, Hyperactive/impulsive subscore) of the ADHD-RS-IV-J by parents.

Total scores and subscores (planning subscore, attention subscore, simultaneous subscore, successive subscore) of DN-CAS (Das-Naglieri Cognitive Assessment System) Japanese Version.

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

Biologocal markers (Serum levels of Pro-BDNF, Mature-BDNF, Oxytocin)

Full Information

NCT ID

NCT02305134

First Posted

November 27, 2014

Last Updated

March 17, 2019

Sponsor

Chiba University

1. Study Identification

Unique Protocol Identification Number

NCT02305134

Brief Title

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

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

June 11, 2015 (Actual)

Primary Completion Date

March 2019 (Actual)

Study Completion Date

March 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chiba University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Attention Deficit Disorder With Hyperactivity Disease, Hyperkinesis, Attention Deficit and Disruptive Behavior Disorders

Keywords

Tipepidine, GIRK

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tipepidine Hibenzate

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo is taken orally after breakfast, after supper, and before for 4 weeks.

Intervention Type

Drug

Intervention Name(s)

Tipepidine Hibenzate

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

The ADHD Rating Scale IV Japanese Version (ADHD-RS-IV-J) by physician.

Description

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).

Time Frame

Changes from baseline in ADHD-RS-IV-J at 4-weeks

Secondary Outcome Measure Information:

Title

Subscores (Inattentive subscore, Hyperactive/impulsive subscore) of the ADHD-RS-IV-J by physician.

Time Frame