UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Investigation of suitable administration-time of GLP-1 receptor agonist on glycemic control in patients with type 2 diabetes: multicenter-randomized non-blind study
Title of the study (Brief title)	Study of suitable administration-time of liraglutide (morning vs. evening): Time study
Region	Japan

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

Objectives
Narrative objectives1	The main purpose of this study is to investigate the suitable adiministratin-time (morning versus evening) of liraglutide using hemoglobin A1c in 14 week and 52 week after initiation of liraglutide-therapy as an index of glycemic control in patients with type 2 diabetes.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Explanatory
Developmental phase

Assessment
Primary outcomes	HbA1c values of patients on baseline and at 14, 52 week after initiation of liraglutide-therapy
Key secondary outcomes	1)Fasting or postprandial plasma glucose, serum lipids, serum C-peptide, IRI,body weight, and blood pressure of patients on baseline and at 14, 38, 52 week after initiation of liraglutide-therapy 2)Change of HbA1c values, plasma glucose levels, serum C-peptide, IRI,serum lipids, body weight, blood pressure of patients on baseline and at 14, 26, 38, 52 week after initiation of liraglutide-therapy 3) Evaluation of side-effects: nausea, vomiting, diarrhea, constipation, hypoglycemic symptom, etc.

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification	YES
Dynamic allocation	YES
Institution consideration
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Enrollment and assignment of patients in 4 weeks before initiation of liraglutide-therapy. Doses of liraglutide are 0.3 mg/day during first 1 week, 0.6 mg/day during next 1 week, and subsequently 0.9 mg/day. All anti-diabetic drugs must be discontinued except sulfonylureas (SU). Doses of SUs should be respectively decreased to glibenclamide 1.25 mg/day, glimepiride 0.5-2mg/day, gliclazide 40 mg/day. Patents will be assigned into 2 groups (morning-adominitration group or evening administration group).Observation of 14 weeks after initiation of liraglutide therapy is needed.
Interventions/Control_2	Doses of SUs should be increased to glibenclamide 2.5 mg/day, glimepiride 3 mg/day, gliclazide 80 mg/day if patients'HbA1c exceeds 8% at 14 weeks. Further 12 weeks-observation is needed. Change liraglutide to insulin (insulin detemir once a day) if patients'HbA1c still exceeds 8% at 26 weeks. Doses of insulin should be adjusted based on each patient's fasting plasma glucose.Change liraglutide from daily administration (once a day) to alternative administration (once a day) if patient's HbA1c are less than 7% at 26 weeks. Further 12 weeks-observation is needed. Change insulin detemir (once a day)- therapy to insulin basal-bolus therapy (insulin detemir once a day with 3 times insulin aspart before each meal) or to multiple-administration of mix-insulin if patients'HbA1c still exceeds 8% at 38 weeks. Further 14 weeks-observation (to 52 weeks) is needed.
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	Not applicable
Gender	Male and Female
Key inclusion criteria	1)Patients age >20 years 2)Patients who are diagnosed as type 2 diabetes 3)Patients treated with diet and exercise alone, or ones with oral anti-diabetic drugs in addition to diet-and exercise-therapy 4)HbA1c of patients>=6.1%JDS (>=6.5%NGSP) 5)Patients who gave a written informed consent for participation for this study
Key exclusion criteria	1)Patients with hypersensitivity for liraglutide 2)Patients who developed diabetic ketoacidosis, diabetic coma 3)Patients with type 1 diabetes 4)Patients with severe infection, liver dysfunction[AST>=80IU/L, ALT>=80IU/L], and renal dysfunction [serum creatinine>=1.7mg/mL] 5)Patients under artificial dialysis 6)Patients with severe heart disease (NYHA3-4) 7)Patients with oral anti-diabetic drugs except for SUs, or insulin at initiation of liraglutide therapy 8)Patients with past history of pancreatitis 9)Patients with diabetic gastroparesis or gastrointestinal disease such as inflammatory bowel disease 10)Patients in pregnancy, during lactation, or having possibility of pregnancy 11)Patients with pasthistory of medullary thyroid cancer,Patients with family history of medullary thyroid cancer,and multiple endocrine neoplasia type 2 12)Patients who was comsident to be inadequate for enrollment in this study by doctors
Target sample size	300

Research contact person
Name of lead principal investigator	Kohzo Takebayashi
Organization	Dokkyo Medical University Koshigaya Hospital
Division name	Internal Medicine
Address	2-1-50, Minamikoshigaya, Koshigaya, Saitama, Japan
TEL	048-965-1111
Email

Public contact
Name of contact person	Kohzo Takebayashi
Organization	Dokkyo Medical University Koshigaya Hospital
Division name	Internal Medicine
Address	2-1-50, Minamikoshigaya, Koshigaya, Saitama, Japan
TEL	+81-48-965-1111
Homepage URL
Email	takebaya@dokkyomed.ac.jp

Sponsor
Institute	Dokkyo Medical University Koshigaya Hospital Internal Medicine
Institute
Department

Funding Source
Organization	None
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

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

Other administrative information
Date of disclosure of the study information	2010 Year 12 Month 25 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2010 Year 10 Month 06 Day
Anticipated trial start date	2011 Year 02 Month 01 Day
Last follow-up date	2013 Year 04 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded	2014 Year 01 Month 01 Day

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2010 Year 12 Month 22 Day
Last modified on	2017 Year 06 Month 30 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005690