UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Effects of Sitagliptin on Glycemic Control and Lipoprotein Metabolism (GLORIA)
Title of the study (Brief title)	Effects of Sitagliptin on Glycemic Control and Lipoprotein Metabolism (GLORIA)
Region	Japan

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

Objectives
Narrative objectives1	To examine the efficacy of Sitagliptin for improving hyperglycemia, lipoprotein metabolism and lipid oxidation markers (HETE, HODE, etc.) in patients with type 2 diabetes
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Not applicable

Assessment
Primary outcomes	Changes in the following items will be evaluated at the beginning of administration and after the 12th week of administration. - Lipid oxidation markers (HODE, HETE)
Key secondary outcomes	-Evaluation of following levels before and after the administration of Sitagliptin >Fasting Glucose >HbA1c(NGSP or JDS) >Triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol >adiponectin, insulin, glucagon >free fatty acids(FFA) >apolipoproteinAI, AII, B, CII, CIII, E, apoB-48 >omentin, RemL-C, CystatinC, endotoxin - Incidence of side effects (hypoglycemia)

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	One 50-mg tablet of Sitagliptin will be orally administered once daily for 12 weeks. Based on the therapeutic target, the dose can be increased to 100 mg.
Interventions/Control_2
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 with type 2 diabetes aged >20 years old who meet the following criteria and have fasting blood glucose (FPG) >126 mg/dL and HbA1c <8.4% (NGSP) or <8.0% (JDS) Patients who have not shown a sufficient response to any of the following treatments described in the package insert 1) Diet therapy and exercise therapy only 2) Use of a sulfonylurea drug in addition to diet therapy and exercise therapy Sulfonylurea drug (Amaryl, Euglucon, Glimicron and Daonil) Patients who meet the following exclusion criteria will be excluded. 3) Use of a thiazolidine drug in addition to diet therapy and exercise therapy Thiazolidine drug (Actos) 4) Use of a biguanide drug in addition to diet therapy and exercise therapy Biguanide drug (Melbin, Glycoran, Dibetos B and Metgluco) 5) Use of an alpha-glucosidase inhibitor in addition to diet therapy and exercise therapy alpha-glucosidase inhibitor (Basen, Seibule and Glucobay) 6) Use of an insulin product in addition to diet therapy and exercise therapy 2. Patients who give written informed consent to participate in the study on a voluntary basis after receiving and understanding a sufficient explanation of the study
Key exclusion criteria	1. Patients with type 1 diabetes 2. Patients with severe renal disorder (including hemodialysis) with a serum creatinine (Cr) level (mg/dL) >2.5 for males and >2.0 for females 3. Patients who have already received a sulfonylurea drug at a higher dose than the following dose: (Amaryl: 2 mg, Euglucon: 1.25 mg, and Glimicron: 40 mg), when it is clinically judged that the dose of the sulfonylurea cannot be decreased when sitagliptin is added. The criteria for a decrease in the dose of the sulfonylurea when sitagliptin is added are as follows: For patients who receive glimepiride (Amaryl) at a dose of >2 mg/day, the dose should be decreased to <2 mg/day. For patients who receive glibenclamide (Euglucon and Daonil) at a dose of >1.25 mg/day, the dose should be decreased to <1.25 mg/day. For patients who receive gliclazide (Glimicron) at a dose of >40 mg/day, the dose should be decreased to <40 mg/day. 4. Patients who have already taken Sitagliptin, Alogliptin, or Vildagliptin. 5. Patients who newly started taking a statin, fibrate, ezetimibe, or probucol within 1 month of the start of the study 6. Patients who are pregnant or may become pregnant 7. Patients receiving treatment for thyroid failure 8. Patients with severe hepatic dysfunction with AST and ALT >100 IU/L 9. Patients who have participated in another clinical study 10. Other patients who judged not to be eligible to participate in the study by their primary physician
Target sample size	100

Research contact person
Name of lead principal investigator	Shizuya Yamashita
Organization	Osaka University Graduate School of Medicine
Division name	Department of Cardiovascular Medicine
Address	2-2 Yamadaoka, Suita, Osaka
TEL	06-6879-3633
Email	shizu@cardiology.med.osaka-u.ac.jp

Public contact
Name of contact person	Daisaku Masuda
Organization	Osaka University Graduate School of Medicine
Division name	Department of Cardiovascular Medicine
Address	2-2 Yamadaoka, Suita, Osaka
TEL	06-6879-3633
Homepage URL
Email	masuda@cardiology.med.osaka-u.ac.jp

Sponsor
Institute	Osaka University Graduate School of Medicine, Department of Cardiovascular Medicine
Institute
Department

Funding Source
Organization	The Supporting Center for Clinical Research and Education
Organization
Division
Category of Funding Organization	Non profit foundation
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	大阪中央病院（大阪府）、蒼生病院（大阪府）、リョーヤコマツクリニック（大阪府）

Other administrative information
Date of disclosure of the study information	2014 Year 02 Month 21 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2012 Year 06 Month 14 Day
Anticipated trial start date	2012 Year 07 Month 01 Day
Last follow-up date	2013 Year 12 Month 31 Day
Date of closure to data entry	2014 Year 12 Month 31 Day
Date trial data considered complete	2014 Year 12 Month 31 Day
Date analysis concluded	2015 Year 03 Month 31 Day

Related information
URL releasing protocol
Publication of results	Published
URL releasing results	https://www.jstage.jst.go.jp/browse/jat
Results	In patients with type II diabetes mellitus, fasting and postprandial hypertriglyceridemia (PHTG) is complicated. PHTG is supposed to be caused by the postprandial accumulation of remnant lipoproteins (VLDL remnants and chylomicron remnants), which are highly atherogenic. In the current study, we investigated whether the sitagliptin might ameliorate the impaired lipoprotein metabolism in patients with type II diabetes mellitus. We enrolled 38 patients with type II diabetes mellitus whose HbA1c levels were less than 8.4% and all patients gave written informed consents. The oral administration of sitagliptin(50mg/day) were started in addition to the current anti-diabetic treatments. The daily dose of sitagliptin was allowed to increase up to 100 mg/day in order to achieve low HbA1c level less than 7.4%. We compared biomarkers concerning glucose and lipoprotein metabolism before and after the administration of sitagliptin for twelve weeks. There were significant decreases in fasting glucose levels and HbA1c levels as well as fasting TG levels and non HDL-C levels. Biomarkers of remnant lipoproteins, fasting apolipoprotein(apo) B-48 and RemL-C levels were significantly decreased by sitagliptin. Moreover, there were significant decreases in other apolipoproteins such as apoB, apoC2, C3 and apoE. Cholesterol and TG concentrations of lipoprotein fractions in the size of VLDL and LDL were significantly decreased by sitagliptin assessed by the high performance liquid chromatography(HPLC) analysis. These findings indicated that the administration of sitagliptin improved the lipid and lipoprotein profile in patients with type II diabetes mellitus, which might be due to the decrease in atherogenic remnant lipoproteins.
Other related information

Management information
Registered date	2014 Year 02 Month 21 Day
Last modified on	2018 Year 08 Month 03 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000015424