UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Brain histamine H1 receptor occupancy of sedating OTC antihistamines: Time-course of receptor occupancy measured by PET in normal volunteers
Title of the study (Brief title)	Histamine H1 receptor occupancy of OTC antihistamines
Region	Japan

Condition
Condition	Normal volunteers
Classification by specialty	Adult
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	Sedating H1 antihistamines are often used in the medication for allergic diseases, coughs and colds, and insomnia, without prescription, even though their sedative properties are a potentially dangerous unwanted side effect that is not properly recognized. These sedative properties have been evaluated using the incidence of subjective sleepiness, objective cognitive and psychomotor functions, and positron emission tomography (PET) measurement of H1 receptor occupancy. This study is designed to evaluate brain histamine H1 receptor occupancy sequentially using carbon-11 doxepin after oral administration of OTC antihistamines containing ketotifen 1.38 mg and diphenhydramine 50 mg in normal volunteers.
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Explanatory
Developmental phase	Phase IV

Assessment
Primary outcomes	Brain histamine H1 receptor occupancy 3 and 23 hours after oral administration of ketotifen 1.38 mg and diphenhydramine 50 mg.
Key secondary outcomes	Subjective sleepiness scale 3 and 23 hours after oral administration of ketotifen 1.38 mg and diphenhydramine 50 mg.

Base
Study type	Interventional

Study design
Basic design	Cross-over
Randomization	Randomized
Randomization unit	Individual
Blinding	Single blind -participants are blinded
Control	Placebo
Stratification	NO
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Numbered container method

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Ketotifen 1.38 mg
Interventions/Control_2	Diphenhydramine 50 mg
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	30 years-old >=
Gender	Male
Key inclusion criteria	1. Normal volunteers with his own free will. There is no subordinate relation. 2. Male healthy volunteers aged 20-30 years old, who understand the purpose of this study. 3. Subjects who can take enough sleep and rest at the previous night of PET scans 4. Subjects who can read documents attached with e-mail. 5. Subjects who can communicate with mobile phones. 6. Subjects who can take 3 PET-sacns examination and 1 MRI scan.
Key exclusion criteria	1. Subjects who take no medication including antihistamines at present. 2. Subjects who do not take any PET scans within the recent 2 years. 3. No serious allergy 4. No convulsion at past 5. No frequent medical addmission 6. No glaucoma and prostatic hypertrophy 7. Subjects who can not take any anticholinergic and antihistaminergic drugs from medical points of view. 8. No brain MRI abnormality 9. Inadequate subjects from the point of medical view of the investigators.
Target sample size	8

Research contact person
Name of lead principal investigator	Yanai Kazuhiko
Organization	Tohoku University Graduate School of Medicine
Division name	Pharmacology
Address	2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575 Japan
TEL	022-717-8055
Email	yanai@med.tohoku.ac.jp

Public contact
Name of contact person	Yanai Kazuhiko
Organization	Tohoku University Graduate School of Medicine
Division name	Pharmacology
Address	2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575 Japan
TEL	022-717-8055
Homepage URL
Email	yanai@med.tohoku.ac.jp

Sponsor
Institute	Department of Pharmacology, Tohoku University Graduate School of Medicine
Institute
Department

Funding Source
Organization	Department of Pharmacology, Tohoku University Graduate School of Medicine NEDO microdose project
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	東北大学大学院医学系研究科機能薬理学分野 Tohoku University Graduate School of Medicine, Department of Pharmacology

Other administrative information
Date of disclosure of the study information	2013 Year 08 Month 05 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2011 Year 02 Month 01 Day
Anticipated trial start date	2013 Year 08 Month 01 Day
Last follow-up date	2015 Year 03 Month 31 Day
Date of closure to data entry	2015 Year 03 Month 31 Day
Date trial data considered complete	2015 Year 03 Month 31 Day
Date analysis concluded	2016 Year 03 Month 31 Day

Related information
URL releasing protocol
Publication of results	Partially published
URL releasing results
Results	Brain histamine H1 receptors were measured using PET and [11C]doxepin at 3 hours and 23 hours consecutively after diphenhydramine (50 mg) or ketotifen (1 mg) intake in healthy, young male subjects. The half-life of diphenhydramine and ketotifen in the brain was estimated to be ~30 hours and 45 hours, respectively.
Other related information	Yanai K, et al. Histamine H1 Receptor Occupancy in Human Brain. In: Histamine Receptors:Preclinical and Clinical Aspects.Springer 2016: pp311-325. ISBN: 978-3-319-40306-9

Management information
Registered date	2013 Year 08 Month 05 Day
Last modified on	2017 Year 10 Month 25 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013278