UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000005283
Receipt number R000004639
Scientific Title Effect of DPP-4 inhibitor on insulin secretion and insulin sensitivity
Date of disclosure of the study information 2011/03/22
Last modified on 2015/03/21 10:23:27

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Basic information

Public title

Effect of DPP-4 inhibitor on insulin secretion and insulin sensitivity

Acronym

3S-OGTT (Staitama Sitagliptin Study with OGTT)

Scientific Title

Effect of DPP-4 inhibitor on insulin secretion and insulin sensitivity

Scientific Title:Acronym

3S-OGTT (Staitama Sitagliptin Study with OGTT)

Region

Japan


Condition

Condition

Type 2 diabetes mellitus

Classification by specialty

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

To examine effects of sitagliptin (a DPP-4 inhibitor) and mitilinide (a glinide compound) on insulin secretion and insulin sensitivity modified by glucagon secretion during OGTT (oral glucose tolerance test)

Basic objectives2

Efficacy

Basic objectives -Others


Trial characteristics_1


Trial characteristics_2


Developmental phase



Assessment

Primary outcomes

AUC (area under the curve) of glucagon response during OGTT between sitagliptin treatment and miglitol treatment

Key secondary outcomes

Markers of insulin secretion and insulin sensitivity and relation between those markers and effect of medication on glycoalbumin, fasting plasma glucose, and 2hr plasma glucose.


Base

Study type

Interventional


Study design

Basic design

Cross-over

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration


Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Subjects who assigned to sitagliptin first, will receive 50mg of sitagliptin per day for 7 days and 100mg of sitaglipitn for additional 7 days. Then they will receive 10mg of mitiglinide tid for 14 days.

Interventions/Control_2

Subjects who assigned to mitiglinide first, will receive 10mg of mitiglinide tid for 14 days. Then they will receive days50mg of sitagliptin per day for 7 days and 100mg of sitaglipitn for additional 7 days.

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

75 years-old >

Gender

Male and Female

Key inclusion criteria

Subjects should be type 2 diabetic patients who have stable glycemic control for more than 2 months, and their HbA1c (NSGP) should be less than 9.4 %. Subjects who are taking pioglitazone or metformin with DPP-4 inhibitors or glinides will be also enrolled.

Key exclusion criteria

1) Under the treatment with insulin
2) Type 1 diabetic subjects or diabetic subjects who have HbA1c (NSGP) more than or equal to 9.4 % or who need admission because of diabetic ketoacidosis or extreme hyperglycemia.
3) Subjects with alpha glucosidase inhibitors.
4) Subjects who are treated with sulfonylureas (i.e. glibenclamide, glimepiride, or gliclazide).
5) Subjects with nephrotic syndrome (urine protein more than or equal to 3.5g/day and serum protein less than or equal to 6.0 g/dl [or serum albumin less than or equal to 3.0 g/dl].
6) Subjects who are taking steroids, immune suppression medication, antifungal medication of azoles. HIV protease inhibitors
7) Subjects with previous serious adverse events (possible and prolonged situations to influence usual daily activity or to add hospital admission duration) with DPP-4 inhibitors and glinides.
8) Subjects who had brain stroke or acute coronary syndrome within 6 months before enrollment.
9) Subjects with severe heart failure (NYHA class 3 or higher), severe arrhythmia (frequent atrial or ventral arrhythmia, continuous ventricular tachycardia, severe atrial tachycardia, atrial fibrillation or flutter with severe tachycardia, sick sinus syndrome or atrial-ventral block with severe bradycardia).
10) Subjects who have AST or ALT more than 5 times of upper normal limit of their institute
11) Subjects with malignancy
12) Subjects who are pregnant or who have intention to be pregnant
13) Subjects with other situations under which a doctor in charge decides that subjects are not eligible for this study.

Target sample size

20


Research contact person

Name of lead principal investigator

1st name
Middle name
Last name Masafumi Matsuda

Organization

Saitama Medical Center, Saitama Medical University

Division name

Department of Endocrinology and Diabetes

Zip code


Address

1981 Kamoda, Kawagoe-shi, Saitama-ken

TEL

049-228-3564

Email

matsudam-ind@umin.ac.jp


Public contact

Name of contact person

1st name
Middle name
Last name Masafumi Matsuda

Organization

Saitama Medical Center, Saitama Medical University

Division name

Department of Endocrinology and Diabetes

Zip code


Address

1981 Kamoda, Kawagoe-shi, Saitama-ken

TEL

049-228-3564

Homepage URL

http://www.glucose-clamp.com/isir

Email

isir@glucose-clamp.com


Sponsor or person

Institute

Study group of incretin in Saitama

Institute

Department

Personal name



Funding Source

Organization

The Waksman Foundation of Japan INC.

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization



Other related organizations

Co-sponsor

None

Name of secondary funder(s)

None


IRB Contact (For public release)

Organization


Address


Tel


Email



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

埼玉医科大学総合医療センター


Other administrative information

Date of disclosure of the study information

2011 Year 03 Month 22 Day


Related information

URL releasing protocol

http://www.glucose-clamp.com/isir

Publication of results

Published


Result

URL related to results and publications

http://www.glucose-clamp.com/isir/index.html

Number of participants that the trial has enrolled


Results

We compared directly these sitagliptin (SIT) and mitiglinide (MIT) in 16 type 2 diabetic patients (M/F=10/6, Age: 66+/-3 y.o., BMI: 24+/-4kg/m2, HbA1c: 6.6+/-0.5%, FPG: 116+/-27mg/dl). Patients received SIT (50mg qd for 1 week and 100mg qd for an additional week) or MIT (10mg tid for 2 weeks). After 2 weeks, patients crossed-over to an alternative treatment. 75 g oral glucose tolerance tests (OGTT) were conducted before the study and after interventions. The average of area under the curve (aAUC) up to 180 min of PG response was similar in both agents and lower than before (CON) (SIT 179+/-53, MIT 174+/-50 vs CON 222+/-60 mg/dl, p<0.0001). Insulinogenic index was highest in MIT (0.3+/-0.3 vs SIT 0.2+/-0.2, p<0.01; vs CON 0.1+/-0.1, p<0.01), while the Matsuda index was similar in 3 OGTTs (MIT 10+/-5, SIT 11+/-7, CON 11+/-7). aAUC of GLP-1 was increased in SIT (15+/-14 vs MIT 6+/-5, p<0.001; vs CON 5+/-4 pmol/L, p<0.001). The incremental aAUC of glucagon was lower in SIT (-2.4+/-12.9 vs MIT 6.2+/-14.0, p<0.05; vs CON -0.7+/-15.0 ng/ml), although basal glucagon levels were paradoxically higher in SIT (77+/-17, vs MIT 71+/-18 p<0.05; vs CON 74+/-20 ng/ml). aAUC of proinsulin was decreased in SIT (15.0+/-3 8, vs MIT 21.4+/-9.8, p<0.01; vs CON 17.2+/-8.6 pmol/L, p<0.05). Triglyceride levels were reduced by MIT. There were no differences between subjects who randomly started with SIT first and those with MIT first. While clinical doses of SIT and MIT resulted in a similar PG control, SIT enhanced less insulin secretion with less glucagon responses and much less proinsulin responses compared with MIT. Thus these changes of hormonal profiles by SIT favor islet functions compared with MIT in clinical use.

Results date posted


Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics


Participant flow


Adverse events


Outcome measures


Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2011 Year 03 Month 01 Day

Date of IRB


Anticipated trial start date

2011 Year 03 Month 01 Day

Last follow-up date

2011 Year 12 Month 01 Day

Date of closure to data entry

2011 Year 12 Month 01 Day

Date trial data considered complete

2011 Year 12 Month 01 Day

Date analysis concluded

2012 Year 03 Month 01 Day


Other

Other related information

Published :
Yoshitaka Akiyama, Tomoko Morita-Ohkubo, Natsuko Oshitani, Yuko Ohno, Yoshimasa Aso, Toshihiko Inukai, Masafumi Kakei, Masanobu Kawakami, Takuya Awata, Shigehiro Katayama and Masafumi Matsuda: Decreased glucagon levels and decreased insulin secretion after sitagliptin versus mitiglinide administration with similar glycemic levels following an oral glucose load: a randomized crossover pharmaceutical mechanistic study. Diabetology International 10.1007/s13340-015-0207-1


Management information

Registered date

2011 Year 03 Month 21 Day

Last modified on

2015 Year 03 Month 21 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000004639


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name