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

NCT02305134 | Completed Phase 1 DMC

• 2 other identifiers: G26023UMIN000015748
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Tipepidine, GIRK

Outcome Measures

Primary Outcomes (1)

• 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).

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

Secondary Outcomes (5)

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

  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

• 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

Study Arms (2)

Tipepidine Hibenzate

ACTIVE COMPARATOR

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

Drug: Tipepidine Hibenzate

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Tipepidine Hibenzate DRUG

Tipepidine Hibenzate

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chiba University: lead

Study Sites (1)

Department of Psychiatry, Chiba University School of Medicine

Chiba, Chuo-ku, 260-8670, Japan

Location

MeSH Terms

Conditions

Hyperkinesis; Attention Deficit and Disruptive Behavior Disorders

Interventions

tipepidine

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Child Psychiatry, Chiba-University Hospital

Study Record Dates

• First Submitted: November 27, 2014
• First Posted: December 2, 2014
• Study Start: June 11, 2015
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: March 19, 2019

Record last verified: 2019-03

Locations

JP (1)