UMIN-CTR Clinical Trial

Public title

Japan Prevention Trial of Diabetes by Pitavastatin in Patients With Impaired Glucose Tolerance (J-PREDICT)

Acronym

Japan Prevention Trial of Diabetes by Pitavastatin in Patients With Impaired Glucose Tolerance (J-PREDICT)

Scientific Title

Japan Prevention Trial of Diabetes by Pitavastatin in Patients With Impaired Glucose Tolerance (J-PREDICT)

Scientific Title:Acronym

Japan Prevention Trial of Diabetes by Pitavastatin in Patients With Impaired Glucose Tolerance (J-PREDICT)

Region

Japan

Condition

Diabetes mellitus

Classification by specialty

Medicine in general	Endocrinology and Metabolism	Nephrology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The purpose of this study is to evaluate the effects of pitavastatin for preventing diabetes in a population with impaired glucose tolerance (IGT).

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase IV

Primary outcomes

Cumulative incidence of diabetes based on 1 positive OGTT or fasting glucose levels

Key secondary outcomes

Cumulative incidence of diabetes based on clinical diagnosis defined as at least one of the following:(1) Typical symptoms of diabetes plus 1 positive OGTT or fasting glucose levels,(2) HbA1c>=6.5% plus 1 positive OGTT or fasting glucose levels, (3) 2 positive OGTT or fasting glucose levels.
The classification and diagnostic criteria of diabetes mellitus have been defined by Japan Diabetes. Society(Diabetes Vol.53,No.6,2010)
; Development of diabetes based on 1 positive OGTT or fasting glucose levels
; New development of diabetes based on 2 positive OGTT or fasting glucose levels
; Cumulative incidence of newly developed diabetes based on 1 positive OGTT or fasting glucose levels (from the first administration of the study drug after the randomization)
; Incidence of newly developed diabetes
; Time until development of diabetes; Improvement in glucose tolerance; Incidence of any cardiovascular disease (myocardial infarction, angina, congestive heart disease, coronary revascularization, cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, transient ischemic attack, arteriosclerosis obliterans, leg amputation, endovascular or surgical intervention in leg arteries, sudden death); Incidence of coronary heart disease (myocardial infarction, angina, coronary revascularization); Incidence of coronary heart disease plus cerebral infarction; LDL-cholesterol; HDL-cholesterol; Triglyceride; RLP-cholesterol; Adiponectin; High sensitive CRP; Asymmetrical dimethyl arginine (ADMA); Urinary 8-OHdG; Fasting plasma glucose; 2-h plasma glucose during 75g oral glucose tolerance test; HbA1c; Insulin; HOMA-R; HOMA-beta; Insulinogenic index
; Time until dropout
; Number of adverse events

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

No need to know

No. of arms

2

Purpose of intervention

Prevention

Type of intervention

Medicine

Behavior,custom

Interventions/Control_1

Group with life-style intervention alone:
As the life-style interventions aiming to reduce the major risks of developing diabetes mellitus, instruct the following four items: (1) set diet right, (2) maintain normal weight, (3) improve physical activity, (4) normalize smoking and alcohol drinking

Interventions/Control_2

Group with life-style interventions plus concomitant use of pitavastatin: once-daily dosing of pitavastatin 1 mg (1 tablet of Livalo Tab 1 mg), or 2 mg (2 tablets of Livalo Tab 1 mg or 1 tablet of Livalo Tab 2 mg); Dosing period of pitavastatin should be 60 months (max. 84 months).

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

75

years-old

>

Gender

Male and Female

Key inclusion criteria

[1] Inclusion Criteria for the screening test (within 6 months before screening)
- Men and women
- Age 30-74
- LDL-cholesterol 100-159 mg/dl and/or total cholesterol 180-239 mg/dl
- At least one of the following:
1) Fasting plasma glucose 100-125 mg/dl, and/or casual (non-fasting) plasma glucose 120-199 mg/dl, and/or HbA1c 5.5-6.0%
2) At least two of the following risk factors for impaired glucose tolerance:
a) Second degree relative with diabetes
b) BMI >= 24 kg/m2
c) Systolic blood pressure >=130 mmHg, and/or diastolic blood pressure >= 85 mmHg, and/or receiving treatment for hypertension
d) Triglyceride >= 150 mg/dl, and/or HDL < 40 mg/dl
- Written consent for participation in the study by their own volition after being provided sufficient explanation for the participation into this clinical trial
[2] Inclusion Criteria for the entry; Confirmed by the screening test
- Impaired glucose tolerance by 75g oral glucose tolerance test (fasting plasma glucose < 126 mg/dl and 2-h plasma glucose 140-199 mg/dl)

Key exclusion criteria

-History of diabetes (except gestational diabetes)
-Fasting plasma glucose >= 126 mg/dl, and/or 2-h plasma glucose >= 200 mg/dl
-HbA1c >= 6.5 %
-Diabetic retinopathy
-Receiving with hormone replacement therapy
-Pancreatic diseases (e.g.pancreatitis, pancreatectomy, pancreatic cancer), Endocrine diseases (e.g. Cushing's syndrome, acromegaly, pheochromocytome, aldosteronism, hyperthyroidism)
-Receiving statins, fibrates or anion exchange resins
-Cancer or suspected cancer
-History of gastrectomy
-History of myocardial infarction, angina, or heart failure (NYHA Class >= III)
-Severe hypertension (SBP >= 180 mmHg or DB` >= 110 mmHg)
-Renal disease, including serum creatinine >= 2.0 mg/dl
-Hepatic disease, including transaminase (ALT or AST) >= 2 times the upper limit of normal
-Women hoping to become pregnant during the intended stury period
-Contraindication or relative contraindication of Livalo Tab (pitavastatin calcium)
a) History of hypersensitivity to any of the ingredients of the product
b) Severe hepatic disorder or biliary atresia
c) Receiving cyclosporine
d) Pregnant women, women suspected of being pregnant, or lactating women
e) Patients receiving fibrates who also have laboratory evidence of abnormal renal function
-Familial hypercholesterolemia
-Drug abuse, alcoholism
-Individuals who are ineligible in the opinion of the investigator

Target sample size

1240

Name of lead principal investigator

1st name
Middle name
Last name	Takashi Kadowaki

Organization

Graduate School of Medicine, the University of Tokyo

Division name

Department of Metabolic Diseases

Zip code

Address

7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan

TEL

03-5800-8815

Email

kadowaki-dm@umin.ac.jp

Name of contact person

1st name
Middle name
Last name	Tsutomu Yamazaki

Organization

Graduate School of Medicine, the University of Tokyo

Division name

Clinical Bioinformatics Study Unit

Zip code

Address

7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan

TEL

03-5800-9844

Homepage URL

Email

yama-tky@umin.ac.jp

Institute

Graduate School of Medicine, the University of Tokyo

Institute

Department

Personal name

Organization

The Waksman Foundation of Japan

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

YES

Study ID_1

NCT00301392

Org. issuing International ID_1

ClinicalTrials.gov

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2013

Year

11

Month

28

Day

URL releasing protocol

Publication of results

Partially published

URL related to results and publications

Number of participants that the trial has enrolled

Results

J-PREDICT
ADA 73rd Scientific Sessions (2013)
Session: Late Breaking Abstracts
Abstract Number: 61-LB
Title: Pitavastatin for the Delay or Prevention of Diabetes Development in Individuals with Impaired Glucose Tolerance
Abstract: Of 8,472 patients who underwent screening, 1,269 individuals with impaired glucose tolerance (IGT) were randomized to either the pitavastatin group (lifestyle modification and pitavastatin [1-2 mg/day]) or the control group (lifestyle modification only).
The diabetes incidence rates for the pitavastatin and control groups were 163 and 186 cases per 1,000 person-years, respectively; the hazard ratio for progression from IGT to diabetes in the pitavastatin group was 0.82 (95% CI: 0.68-0.99; P = 0.041). Even in any subgroups, pitavastatin did not accelerate the incidence, unlike the effects of statins in previous reports. Pitavastatin in combination with lifestyle modification was associated with a lower incidence of diabetes than was lifestyle modification alone in Japanese patients with IGT. Statins are now used with the understanding that a slightly increased risk of diabetes is outweighed by cardiovascular benefits of the drugs. However, based on our results, it may be necessary to reconsider whether all statins really increase the risk of developing diabetes.

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

Completed

Date of protocol fixation

2006

Year

01

Month

25

Day

Date of IRB

Anticipated trial start date

2006

Year

04

Month

01

Day

Last follow-up date

2012

Year

03

Month

31

Day

Date of closure to data entry

2012

Year

06

Month

28

Day

Date trial data considered complete

2012

Year

10

Month

03

Day

Date analysis concluded

2012

Year

10

Month

13

Day

Other related information

Registered date

2013

Year

11

Month

28

Day

Last modified on

2018

Year

09

Month

25

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014547