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Effect of Pravastatin in the Subjects With Prediabetes or Early Diabetes

Primary Purpose

Diabetes Mellitus, Prediabetic State

Status

Completed

Phase

Phase 4

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Pravastatin

Placebo (for Pravastatin)

Nutritional education only

About this trial

This is an interventional treatment trial for Diabetes Mellitus focused on measuring Pravastatin, Insulin Resistance

Eligibility Criteria

20 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects have early diabetes mellitus or prediabetes. Early diabetes mellitus or prediabetes are defined according to the following criteria; Subjects have two or more of the following three, or they have one of them at the initial test and the repeat test.
1. hemoglobin A1C 5.7-9.0%
2. fasting plasma glucose level 100mg/dL or more
3. plasma glucose level 140mg/dL or more at 2 hours after 75g oral glucose tolerance test
Subjects have one of the following three;
1. Low-density lipoprotein cholesterol (LDL-cholesterol) 130mg/dL or more, and body mass index (BMI) > 23 kg/m2,
2. 10 year atherosclerotic cardiovascular disease (ASCVD) risk of 7.5% or more, which is assessed by the ASCVD-Risk-Estimator (Circulation.2014;129:S1-S45)
3. In diabetic patients, LDL-cholesterol 100mg/dL or more

Exclusion Criteria:

Hemoglobin A1C > 9.0%
History of statin use in three months
Use of oral antidiabetic drugs except for metformin in three months
History of malignant diseases (cancers)
History of coronary artery diseases, heart failure, arrhythmia, valvular heart diseases, or cerebrovascular diseases
Pregnant
serum creatinine level > 1.5 mg/dL
aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels higher than 80 U/l
Taking weight loss medications, corticosteroids, Angiotensin converting enzyme (ACE) inhibitors, or estrogen replacement therapy
Chronic hepatitis B or chronic hepatitis C

Sites / Locations

Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Other

Arm Label

Pravastatin

Placebo

Open-label control

Arm Description

Pravastatin 40mg tablet by mouth, once daily for 24 weeks. Also, nutritional education was provided to participants in all arms by a nutritionist, and participants were instructed to follow the educated guideline.

Placebo drug indistiguishable from pravastatin 40mg tablet, by mouth, once daily for 24 weeks. Also, nutritional education was provided to participants in all arms by a nutritionist, and participants were instructed to follow the educated guideline.

No medication. Only nutritional education was provided to participants by a nutritionist, and participants were instructed to follow the educated guideline.

Outcomes

Primary Outcome Measures

Insulin resistance assessed by HOMA-IR (homeostatic model assessment index for insulin resistance)

compared to the HOMA-IR level calculated at the initial visit (at the beginning of the 24 weeks of medication period)

Secondary Outcome Measures

Insulin resistance assessed by Matsuda index calculated through 75g oral glucose tolerance test

calculated according to a method described in a previous study (Matsuda M et al. Diabetes Care, 1999), compared to the results at the initial visit (at the beginning of the 24 weeks of medication period). It takes 120 minutes to perform 75g oral glucose tolerance test

Insulin secretion capacity assessed by insulinogenic index (INS index) during 75g oral glucose tolerance test

the ratio relating enhancement of circulating insulin in 30min [in pmol/L] to magnitude of corresponding glycemic stimulus in 30min [in mmol/L] during the oral glucose tolerance test (H.S. Seltze et al. J. Clin. Investig., 1967), compared to the results at the initial visit (at the beginning of the 24 weeks of medication period)

Insulin resistance assessed by the quantitative insulin sensitivity check index (QUICKI)

calculated using fasting insulin in uIU/mL and fasting plasma glucose in mg/dL according to the method described in a previous study (A. Katz et al. J. Clin. Endocrinol. Metab., 2000), compared to the results at the initial visit (at the beginning of the 24 weeks of medication period)

Insulin secretory capacity relative to insulin resistance assessed by the oral disposition index

calculated according to a method described in a previous study (K.M. Utzschneider et al.Diabetes Care, 2008), compared to the results at the initial visit (at the beginning of the 24 weeks of medication period)

Glycemic control evaluated by fasting glucose level (mg/dL)

compared to the values at the initial visit

Glycemic control evaluated by hemoglobin A1C (%)

compared to the values at the initial visit

Plasma adioponectin level (μg/ml), an adipocyte-derived insulin-sensitizing hormone level

compared to the values at the initial visit

Biomarkers predicting cardiovascular diseases, assessed by high sensitive C-reactive protein (hsCRP) (mg/dL)

compared to the values at the initial visit

Biomarkers predicting cardiovascular diseases, assessed by plasminogen activator inhibitor-1 (PAI-1) (ng/mL)

compared to the values at the initial visit

Full Information

NCT ID

NCT02754739

First Posted

April 9, 2016

Last Updated

September 11, 2018

Sponsor

Samsung Medical Center

Collaborators

Daiichi Sankyo Korea Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT02754739

Brief Title

Effect of Pravastatin in the Subjects With Prediabetes or Early Diabetes

Official Title

Effect of Pravastatin in the Subjects With Prediabetes or Early Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Completed

Study Start Date

April 15, 2014 (Actual)

Primary Completion Date

August 31, 2017 (Actual)

Study Completion Date

August 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Samsung Medical Center

Collaborators

Daiichi Sankyo Korea Co., Ltd.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

An increased risk of incident diabetes with statin therapy have been reported in several studies. However, it is not recommended to limit the use of statin for this reason since the absolute risk increase was small, and the cardiovascular event rate reduction with statins overweighed the risk of new diabetes (Scatter N et al. Lancet, 2010). Moreover, each statin may have different effect on the development of incident diabetes. In the West of Scotland Coronary Prevention Study, pravastatin therapy reduced the hazard of becoming diabetic by 30%. Also, with pravastatin use, an increase in adiponectin level, which is related to the improvement in insulin sensitivity, has been reported. In this clinical trial, the investigators are aiming to evaluate the effect of pravastatin on insulin resistance, insulin secretion, glycemic control, and adiponectin level in participants with prediabetes or early diabetes by assigning them in a 24 weeks of pravastatin therapy group or in a placebo group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Prediabetic State

Keywords

Pravastatin, Insulin Resistance

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Masking Description

This study was initially designed as a single center, double-blind, placebo-controlled, 2-group factorial randomized trial (placebo or pravastatin 40mg once daily for 24 weeks). Subjects were randomly assigned, in a 1:1 ratio, to receive pravastatin in a blinded fashion at a dose of 40 mg once daily or placebo. However, because of the problem of expiration date of the placebo drug, the study was converted to an open-label trial, and subjects without any medications were enrolled in an open-label control group in contrast to the pravastatin group. Therefore, the study cohort comprised the pravastatin group, placebo group, and the open-label control group. The placebo group and the open-label control group were classified as the control group.

Allocation

Randomized

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pravastatin

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

Open-label control

Arm Type

Other

Arm Description

No medication. Only nutritional education was provided to participants by a nutritionist, and participants were instructed to follow the educated guideline.

Intervention Type

Drug

Intervention Name(s)

Pravastatin

Intervention Description

Pravastatin 40mg once daily for 24 weeks and nutritional education by a nutritionist

Intervention Type

Drug

Intervention Name(s)

Placebo (for Pravastatin)

Intervention Description

Pill manufactured to mimic pravastatin 40mg tablet once daily for 24 weeks and nutritional education by a nutritionist

Intervention Type

Behavioral

Intervention Name(s)

Nutritional education only

Other Intervention Name(s)

Open-label control

Intervention Description

Only nutritional education by a nutritionist

Primary Outcome Measure Information:

Title

Insulin resistance assessed by HOMA-IR (homeostatic model assessment index for insulin resistance)

Description

compared to the HOMA-IR level calculated at the initial visit (at the beginning of the 24 weeks of medication period)

Time Frame