UMIN-CTR Clinical Trial

Public title

Program of vascular evaluation under
glucose control by DPP-4 inhibitor

Acronym

PROLOGUE

Scientific Title

Program of vascular evaluation under
glucose control by DPP-4 inhibitor

Scientific Title:Acronym

PROLOGUE

Region

Japan

Condition

Type 2 diabetes

Classification by specialty

Medicine in general	Cardiology	Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate efficacy of a DDP-4 inhibitor in prevention of progression of atherosclerosis by comparing patients receiving a DPP-4 inhibitor to those receiving standard treatment based on carotid-artery intima-media thickness (IMT) assessed by ultrasonography. Effects on cardiovascular function and blood biomarkers are also evaluated. Sitagliptin is used as a DDP-4 inhibitor.

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

The % changes of the mean IMT value after 24 months from the baseline which assessed by ultrasonography.

Key secondary outcomes

1) The measured value of ultrasonography and the % changes and variation at the point of baseline, and at after 12 and 24 months.
Common carotid artery: excluding the % of changes at the point of 24 months.
Sphere, Internal carotid artery: the maximum IMT value, plaque area, plaque luminance

2) Laboratory test values indicated below at baseline, and after 12 and 24 months, and changes and %changes in the values from baseline.
NT-proBNP, high-sensitivity CRP, 1,5AG, small-dense LDL, high-molecular-weight adiponectin, RLP-C, and MDA-LDL

3) Laboratory test values indicated below at baseline, and after 3, 6, 12 and 24 months, and changes and %changes in the values from baseline.
HbA1c, fasting blood glucose, insulin, serum lipids (TC,HDL-C, and TG), serum creatinine, urinary albumin excretion (creatinine corrected value), eGFR (converted value), HOMA-beta and HOMA-R (converted values) and cystatin C

4) Cardiovascular function parameters indicated below at baseline, and after 12 and 24 months, and changes and %changes in the values from baseline.
Echocardiogram (systolic and diastolic function, left atrial dimension, and left ventricular mass index), flow-mediated dilation (FMD), pulse wave velocity (PWV), cardio-ankle vascular Index (CAVI), and atherogenic index (AI)

5) Values indicated below at baseline, and after 3, 6, 12 and 24 months, changes and %changes in the values from baseline, and incidence of significant clinical symptoms.
Blood pressure (ambulant), weight and incidence of significant weight change, and incidence of hypoglycemia symptoms

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Group receiving sitagliptin (DPP-4 inhibitor treated group)

Interventions/Control_2

Group receiving standard treatment (non-DPP-4 inhibitor treated 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

Age-lower limit

30

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Patients with type 2 diabetes who had received diet and exercise therapy or diet, exercise and pharmacologic therapy with oral antidiabetic agents other than a DPP-4 inhibitor for more than 3 months and whose blood glucose have not been sufficiently controlled (5.8% <= HbA1c(JDS) < 9.0%)
2) Outpatients aged >= 30 years of both sexes
3) Patients who have given written informed consent to participate in the study

Key exclusion criteria

1) Patients with type 1 diabetes
2) Patients who had a history of severe ketosis, diabetic coma or precoma within 6 months
3) Patients before or after operation, and those with severe infections or serious injury
4) Patients with severe kidney dysfunction (eGFR: <30 mL/min or patients under dialysis)
5) Patients who had myocardial infarction, angina, percutaneous transluminal coronary angioplasty / bypass surgery, cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, or transient cerebral ischemic attack within 3 months before the study initiation.
6) Patients with moderate or severe cardiac dysfunction (NYHA class III or IV)
7) Patients who are being treated with a DPP-4 inhibitor or glucagon-like peptide-1 (GLP-1) analog at the time of the study initiation
8) Patients who are being treated with insulin at the time of the study initiation
9) Pregnant, possible pregnant, or lactating women
10) Patients with a history of hypersensitivity to the study drug
11) Patients who are considered not eligible for the study by the attending doctor due to other reasons

Target sample size

500

Name of lead principal investigator

1st name
Middle name
Last name	Koichi Node/Toyoaki Murohara

Organization

Saga University/Nagoya University

Division name

Department of Cardiovascular Medicine

Zip code

Address

5-1-1 Nabeshima, Saga-shi, Saga / 65 Tsurumai-cho ,Showa-ku, Nagoya-shi, Aichi

TEL

0952-34-2364

Email

node@cc.saga-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Junichi Oyama

Organization

Study group for diabetes mellitus and vascular lesion

Division name

Secretariat

Zip code

Address

5-1-1Nabeshima, Saga-shi, Saga

TEL

0952-34-2364

Homepage URL

Email

junoyama@cc.saga-u.ac.jp

Institute

Study group for diabetes mellitus and vascular lesion secretariat

Institute

Department

Personal name

Organization

Clinical Research Foundation

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Japan

Co-sponsor

Hokkaido univ,Akita univ,Dokkyo Medical univ,Tskuba univ,Showa univ,Nippon Medical univ,Tokyo Wemen's Medical univ,Juntendo univ,Tokyo Medical univ,Yokohama City univ,Mie univ,Osaka univ,etc

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

北海道大学（北海道）、秋田大学（秋田県）、獨協医科大学（栃木県）、筑波大学（茨城県）、昭和大学（東京都）、日本医科大学（東京都）、東京女子医大（東京都）、順天堂大学（東京都）、東京医科大学（東京都）、横浜市立大学（神奈川県）、名古屋大学（愛知県）、三重大学（三重県）、大阪大学（大阪府）、大阪市立大学（大阪府）、国立循環器病研究センター（大阪府）、徳島大学（徳島県）、川崎医科大学（岡山県）、広島大学（広島県）、広島市立広島市民病院（広島県）、島根大学（島根県）、長崎大学（長崎県）、琉球大学（沖縄県）、佐賀大学（佐賀県）、トヨタ記念病院（愛知県）、北光記念病院（北海道）、津島市民病院（愛知県）、名古屋掖済会病院（愛知県）、四日市社会保険病院（愛知県）、大村市民病院（長崎県）、松崎内科循環器科（長崎県）、小牧市民病院（愛知県）、徳島県立中央病院（徳島県）、一宮市立市民病院（愛知県）、春日井市民病院（愛知県）、名古屋第一赤十字病院（愛知県）、西尾市民病院（愛知県）、宮崎大学（宮崎県）、三菱名古屋病院（愛知県）、名古屋セントラル病院（愛知県）、名古屋第二赤十字病院（愛知県）、藤田保健衛生大学坂文種報徳會病院（愛知県）、安城更生病院（愛知県）、北松中央病院（長崎県）、土岐市立総合病院（岐阜県）、岐阜県立多治見病院（岐阜県）、佐世保市立総合病院（長崎県）、常滑市民病院（愛知県）、長崎川棚医療センター（長崎県）、光晴会病院（長崎県）、国立長寿医療研究センター病院（愛知）、江南厚生病院（愛知）、ブラザー記念病院（愛知）、　公立陶生病院
（愛知）、半田市立半田病院（愛知）、中部ろうさい病院（愛知）、中日病院（愛知）、名城病院（愛知）、国立名古屋医療センター（愛知）、名古屋共立病院（愛知）、海南病院　（愛知）、佐世保中央病院（長崎）、市立四日市病院（三重）、東京医科大学茨城医療センター（茨城）、中津川市民病院（岐阜）、宮崎市郡医師会病院（宮崎）、上田脳神経外科（宮崎）、山元記念病院（佐賀）、佐賀記念病院（佐賀）、ふじおか病院（佐賀）、内藤医院北山診療所（佐賀）、江口病院（佐賀）、ひらまつ病院（佐賀）、池田内科・皮膚科医院（佐賀）、佐賀県立病院好生館（佐賀）、佐賀市立富士大和温泉病院（佐賀）、関東労災病院　（神奈川）、長崎北病院（長崎）、ヨゼフクリニック（長崎）、長崎市立市民病院（長崎）、寺沢病院（徳島）、徳島市民病院（徳島）、高木病院（福岡）

Date of disclosure of the study information

2010

Year

11

Month

01

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

Results

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

Recruitment status

Main results already published

Date of protocol fixation

2010

Year

09

Month

19

Day

Date of IRB

Anticipated trial start date

2010

Year

12

Month

01

Day

Last follow-up date

2014

Year

10

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2010

Year

11

Month

01

Day

Last modified on

2017

Year

05

Month

12

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005356