UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Effects of Linagliptin on Hypoglycemia :Hypoglycemic Clamp Test in Japanese T2DM Patients
Title of the study (Brief title)	Hypoglycemic Clamp Test in Japanese T2DM Patients
Region	Japan

Condition
Condition	Type 2 diabetes
Classification by specialty	Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To show that the glucagon secretion to hypoglycemia is significantly enhanced by biologically intact GIP elevated by linagliptin treatment.
Basic objectives2	Others
Basic objectives -Others	To explore the hormonal response (i.e. Epinephrine, Norepinephrine, Cortisol, GH) to hypo-glycemic condition before and after the linagliptin/liragltide treatment.
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	To explore the change in the following measurements during hypoglycemic (45mg/dL glucose) clamp at 2 weeks after Linagliptin/Liraglutide treatment: (1)Changes in plasma levels of glucagon (2)Its correlation with biologically intact GIP
Key secondary outcomes	To explore the change in the following measurements during hypoglycemic (45mg/dL glucose) clamp at 2weeks after Linagliptin/Liraglutide treatment: (1)ISR, ISR/Glucose (2)Pancreatic and autonomic hormonal response to hypoglycemia(Epinephrine, Norepinephrine, Cortisol, GH)

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Cluster
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is not considered as adjustment factor.
Blocking
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	DPP-4 inhibitor(Linagliptin) group
Interventions/Control_2	GLP-1 receptor agonist(Liraglutide) group
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	40 years-old <=
Age-upper limit	70 years-old >=
Gender	Male and Female
Key inclusion criteria	(1)Japanese T2DM patients (2)Patients treated with 1OAD or not treated with OAD (3)HbA1c (NGSP) 6.0 - 8.0 at screening visit (for patient treated with 1OAD) 6.0 - 8.5 (for patient not treated with OAD) at screening visit (regardless of sex) (5)BMI<30kg/m2
Key exclusion criteria	(1)Patients with diabetes requiring insulin therapy (insulin intensive therapy, T1DM, etc) (2)Patients currently treated with Insulin, DPP-4inhibitor, GLP-1 receptor agonist within 4 weeks and/or treated with Pioglitazon within 12weeks (3)Patients currently treated with alpha blocker, beta blocker, selective serotonin reuptake inhibitors (4)Patients with history of cerebrovascular and cardiovascular disease (5)Patients with heart failure with NYHA I-IV (6)Patients with renal dysfunction (7)Patients with severe hepatic dysfunction (8)Patients with history of pancreatitis (9)Patients with diabetic retinopathy (proliferative retinopathy, vitreous hemorrhage and more severe condition) (10)Patients with autonomic neuropathy (11)Patients with a history of surgery of gastrointestinal tract (12)Patients with malignant tumor (13)Patients with severe infection, in the perioperative period or with serious injury (14)Excessive alcohol intake (15)Patients with hemoglobin (Hb) <13.0g/dL(male), <12.5g/dL(female) (16)Patients found ineligible as a study patient according to the discretion of the investigator or sub-investigator (17)Patients participating in other clinical studies (18)Pregnant or possibly pregnant women (19)Patients judged as inadequate to participate in present study by investigator or sub-investigator
Target sample size	35

Research contact person
Name of lead principal investigator	Daisuke Yabe
Organization	Kansai Electric Power Hospital
Division name	Center for Diabetes, Endocrinology and Metabolism
Address	2-1-7 Fukushima, Fukushima-ku, Osaka, Japan
TEL	+81-6-6458-5821
Email	ydaisuke-kyoto@umin.ac.jp

Public contact
Name of contact person	Daisuke Yabe
Organization	Kansai Electric Power Hospital
Division name	Center for Diabetes, Endocrinology and Metabolism
Address	2-1-7 Fukushima, Fukushima-ku, Osaka, Japan
TEL	+81-6-6458-5821
Homepage URL
Email	ydaisuke-kyoto@umin.ac.jp

Sponsor
Institute	Kansai Electric Power Hospital
Institute
Department

Funding Source
Organization	Nippon Boehringer Ingelheim Co.,Ltd.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Medical Co. LTA HAKATA CLINIC
Name of secondary funｄer(s)	Eli Lilly & Co.

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	医療法人相生会　博多クリニック（福岡県）/Medical Co.LTA HAKATA CLINIC (Fukuoka) 関西電力病院（大阪府）/ Kansai Electric Power Hospital (Osaka)

Other administrative information
Date of disclosure of the study information	2014 Year 07 Month 01 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2014 Year 06 Month 18 Day
Anticipated trial start date	2014 Year 07 Month 05 Day
Last follow-up date	2015 Year 04 Month 20 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Published
URL releasing results	http://onlinelibrary.wiley.com/doi/10.1111/dom.12817/full
Results
Other related information

Management information
Registered date	2014 Year 06 Month 29 Day
Last modified on	2016 Year 12 Month 09 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000016773