Clinical trial NCT02754739: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus
Prediabetic State
Keywords: Pravastatin
Insulin Resistance
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
Collaborators: name: Daiichi Sankyo Korea Co., Ltd.
First posted: 2016-04-28
Enrollment: 44
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Insulin resistance assessed by HOMA-IR (homeostatic model assessment index for insulin resistance)
timeFrame: at the end of the 24 weeks of medication period
Secondary outcomes:
measure: Insulin resistance assessed by Matsuda index calculated through 75g oral glucose tolerance test
timeFrame: at the end of the 24 weeks of medication period
measure: Insulin secretion capacity assessed by insulinogenic index (INS index) during 75g oral glucose tolerance test
timeFrame: at the end of the 24 weeks of medication period
measure: Insulin resistance assessed by the quantitative insulin sensitivity check index (QUICKI)
timeFrame: at the end of the 24 weeks of medication period
measure: Insulin secretory capacity relative to insulin resistance assessed by the oral disposition index
timeFrame: at the end of the 24 weeks of medication period
measure: Glycemic control evaluated by fasting glucose level (mg/dL)
timeFrame: at the end of the 24 weeks of medication period
measure: Glycemic control evaluated by hemoglobin A1C (%)
timeFrame: at the end of the 24 weeks of medication period
measure: Plasma adioponectin level (μg/ml), an adipocyte-derived insulin-sensitizing hormone level
timeFrame: at the end of the 24 weeks of medication period
measure: Biomarkers predicting cardiovascular diseases, assessed by high sensitive C-reactive protein (hsCRP) (mg/dL)
timeFrame: at the end of the 24 weeks of medication period
measure: Biomarkers predicting cardiovascular diseases, assessed by plasminogen activator inhibitor-1 (PAI-1) (ng/mL)
timeFrame: at the end of the 24 weeks of medication period
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
Study officials:
affiliation: Samsung Medical Center
name: Moon-Kyu Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, Macfarlane PW, Packard CJ, Stott DJ, Westendorp RG, Shepherd J, Davis BR, Pressel SL, Marchioli R, Marfisi RM, Maggioni AP, Tavazzi L, Tognoni G, Kjekshus J, Pedersen TR, Cook TJ, Gotto AM, Clearfield MB, Downs JR, Nakamura H, Ohashi Y, Mizuno K, Ray KK, Ford I. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010 Feb 27;375(9716):735-42. doi: 10.1016/S0140-6736(09)61965-6. Epub 2010 Feb 16.
citation: Rajpathak SN, Kumbhani DJ, Crandall J, Barzilai N, Alderman M, Ridker PM. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care. 2009 Oct;32(10):1924-9. doi: 10.2337/dc09-0738.
citation: Freeman DJ, Norrie J, Sattar N, Neely RD, Cobbe SM, Ford I, Isles C, Lorimer AR, Macfarlane PW, McKillop JH, Packard CJ, Shepherd J, Gaw A. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation. 2001 Jan 23;103(3):357-62. doi: 10.1161/01.cir.103.3.357.
citation: Guclu F, Ozmen B, Hekimsoy Z, Kirmaz C. Effects of a statin group drug, pravastatin, on the insulin resistance in patients with metabolic syndrome. Biomed Pharmacother. 2004 Dec;58(10):614-8. doi: 10.1016/j.biopha.2004.09.005.
citation: Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999 Sep;22(9):1462-70. doi: 10.2337/diacare.22.9.1462.
citation: Seltzer HS, Allen EW, Herron AL Jr, Brennan MT. Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest. 1967 Mar;46(3):323-35. doi: 10.1172/JCI105534.
citation: Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000 Jul;85(7):2402-10. doi: 10.1210/jcem.85.7.6661.
citation: Utzschneider KM, Prigeon RL, Faulenbach MV, Tong J, Carr DB, Boyko EJ, Leonetti DL, McNeely MJ, Fujimoto WY, Kahn SE. Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care. 2009 Feb;32(2):335-41. doi: 10.2337/dc08-1478. Epub 2008 Oct 28.