Effect of Pravastatin in the Subjects With Prediabetes or Early Diabetes

Sponsor

Samsung Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT02754739

Collaborator

Daiichi Sankyo Korea Co., Ltd. (Industry)

Enrollment

Location

Arms

40.5

Actual Duration (Months)

1.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus Prediabetic State	Drug: Pravastatin Drug: Placebo (for Pravastatin) Behavioral: Nutritional education only	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

Randomized

Intervention 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.

Primary Purpose:

Treatment

Official Title:

Effect of Pravastatin in the Subjects With Prediabetes or Early Diabetes

Actual Study Start Date :

Apr 15, 2014

Actual Primary Completion Date :

Aug 31, 2017

Actual Study Completion Date :

Aug 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pravastatin 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.	Drug: Pravastatin Pravastatin 40mg once daily for 24 weeks and nutritional education by a nutritionist
Placebo Comparator: Placebo 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.	Drug: Placebo (for Pravastatin) Pill manufactured to mimic pravastatin 40mg tablet once daily for 24 weeks and nutritional education by a nutritionist
Other: Open-label control No medication. Only nutritional education was provided to participants by a nutritionist, and participants were instructed to follow the educated guideline.	Behavioral: Nutritional education only Only nutritional education by a nutritionist Other Names: Open-label control

Arm

Intervention/Treatment

Experimental: Pravastatin

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.

Drug: Pravastatin

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

Placebo Comparator: Placebo

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.

Drug: Placebo (for Pravastatin)

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

Other: Open-label control

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

Behavioral: Nutritional education only

Only nutritional education by a nutritionist

Other Names:

Open-label control

Outcome Measures

Primary Outcome Measures

Insulin resistance assessed by HOMA-IR (homeostatic model assessment index for insulin resistance) [at the end of the 24 weeks of medication period]
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 [at the end of the 24 weeks of medication period]
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 [at the end of the 24 weeks of medication period]
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) [at the end of the 24 weeks of medication period]
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 [at the end of the 24 weeks of medication period]
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) [at the end of the 24 weeks of medication period]
compared to the values at the initial visit
Glycemic control evaluated by hemoglobin A1C (%) [at the end of the 24 weeks of medication period]
compared to the values at the initial visit
Plasma adioponectin level (μg/ml), an adipocyte-derived insulin-sensitizing hormone level [at the end of the 24 weeks of medication period]
compared to the values at the initial visit
Biomarkers predicting cardiovascular diseases, assessed by high sensitive C-reactive protein (hsCRP) (mg/dL) [at the end of the 24 weeks of medication period]
compared to the values at the initial visit
Biomarkers predicting cardiovascular diseases, assessed by plasminogen activator inhibitor-1 (PAI-1) (ng/mL) [at the end of the 24 weeks of medication period]
compared to the values at the initial visit

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 79 Years

Sexes Eligible for Study:

All

Accepts 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.

hemoglobin A1C 5.7-9.0%
fasting plasma glucose level 100mg/dL or more
plasma glucose level 140mg/dL or more at 2 hours after 75g oral glucose tolerance test

Subjects have one of the following three;

Low-density lipoprotein cholesterol (LDL-cholesterol) 130mg/dL or more, and body mass index (BMI) > 23 kg/m2,
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)
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine	Seoul		Korea, Republic of	135-710