LIpid Lowering With Highly Potent Statins in Hyperlipidaemia With Type 2 Diabetes patiENts (LISTEN)

Study on Effect of Highly Potent Statins on Lipid Lowering Effect and Glucose Metabolism in Hypercholesterolemia Patients With Diabetes Mellitus

The purpose of this study is to compare the effect of rosuvastatin and atorvastatin on lipid lowering effect and glucose metabolism in hypercholesterolemia patients with diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia With Concomitant Type 2 Diabetes
• Intervention / Treatment: Drug: Atorvastatin; Drug: Rosuvastatin

• Study Type: Interventional
• Enrollment (Actual): 1049
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Gifu city, Japan
    • Yasue Naika
  • Aichi pref.
    • Nagoya city, Aichi pref., Japan
      • Hiramitsu Heart Clinic
  • Akita pref.
    • Yurihonjo city, Akita pref., Japan
      • Honjo Daiichi Hospital
  • Chiba pref.
    • Matsudo city, Chiba pref., Japan
      • Iryouhoujin Syadan Yanagisawakai Yanagisawa Iin
  • Ehime pref.
    • Iyo gun, Ehime pref., Japan
      • Matsuno Medical Clinic
    • Matsuyama city, Ehime pref., Japan
      • Ishite Matsumoto Naika Junkanki Clinic
    • Niihama city, Ehime pref., Japan
      • Ehime Medical CO OP Izumigawa Clinic
  • Fukui pref.
    • Fukui city, Fukui pref., Japan
      • Fukui Chuoh Clinic
  • Fukuoka pref.
    • Fukuoka city, Fukuoka pref., Japan
      • Saku Hospital
    • Fukuoka city, Fukuoka pref., Japan
      • Fukuoka City Medical Association Hospital
    • Fukuoka city, Fukuoka pref., Japan
      • Matsumoto Clinic
    • Fukuoka city, Fukuoka pref., Japan
      • Soejima Medical Clinic
    • Fukuoka city, Fukuoka pref., Japan
      • Takei's Clinic Internal Medicine
    • Itoshima city, Fukuoka pref., Japan
      • Nakamura Cardiovascular Clinic
    • Kitakyushu city, Fukuoka pref., Japan
      • Morizono Naika
  • Fukushima pref.
    • Koriyama city, Fukushima pref., Japan
      • Seino Internal Medicine Clinic
  • Gifu pref.
    • Gifu city, Gifu pref., Japan, Japan
      • Kawade Iin
    • Gifu city, Gifu pref., Japan
      • Hashimoto Naika Clinic
    • Gifu city, Gifu pref., Japan
      • Iinuma Iin
    • Gifu city, Gifu pref., Japan
      • Ishimura Clinic
    • Gifu city, Gifu pref., Japan
      • Kawai Clinic
    • Gifu city, Gifu pref., Japan
      • Niimi Clinic
    • Gifu city, Gifu pref., Japan
      • Takai Clinic
    • Kakamigahara city, Gifu pref., Japan
      • Kobayashi Internal Medicine
    • Motosu city, Gifu pref., Japan
      • Horibe Clinic
    • Ogaki, Gifu pref., Japan
      • Kondo Cardiovascular Clinic
    • Ogaki, Gifu pref., Japan
      • Yoshida Naika
  • Gunma pref.
    • Maebashi city, Gunma pref., Japan
      • Kogure Clinic
    • Shibukawa city, Gunma pref., Japan
      • Nakano Clinic
    • Takasaki city, Gunma pref., Japan
      • Yoshii Central Clinic
  • Hiroshima pref.
    • Miyoshi city, Hiroshima pref., Japan
      • Shigenobu Clinic
  • Hokkaido pref.
    • Hakodate city, Hokkaido pref., Japan
      • Takahashi Kiyohito Clinic
    • Sapporo city, Hokkaido pref., Japan
      • Hokuto Internal Medicine Clinic
  • Hyogo pref.
    • Amagasaki city, Hyogo pref., Japan
      • Katsuya Clinic
    • Himeji city, Hyogo pref., Japan
      • Nakatani Hospital
    • Kako gun, Hyogo pref., Japan
      • Kosumo Clinic
    • Kakogawa, Hyogo pref., Japan
      • Harima Clinic
    • Kobe city, Hyogo pref., Japan
      • Kusunose Clinic
  • Ishikawa pref.
    • Hakusan city, Ishikawa pref., Japan
      • Yanagi Medical Clinic
    • Ishikawa gun, Ishikawa pref., Japan
      • Okyozuka Clinic
    • Kanazawa city, Ishikawa pref., Japan
      • Wakasa Medical Clinic
    • Kanazawa city, Ishikawa pref., Japan
      • Doniwa Clinic
  • Iwate pref.
    • Iwate gun, Iwate pref., Japan
      • Association Medical Corporation Neurology Internal Medicine Kanamori Clinic
    • Morioka city, Iwate pref., Japan
      • Medical Corporation Kuon-kai Kamata Medical Clinic
  • Kagawa pref.
    • Marugame city, Kagawa pref., Japan
      • Kagawa Clinic
    • Takamatsu city, Kagawa pref., Japan
      • Hasegawa Outpatients Clinic for Cardiovascular Disease
  • Kagoshima pref.
    • Kagoshima city, Kagoshima pref., Japan
      • Tempozan Naika Clinic
  • Kanagawa pref.
    • Ayase city, Kanagawa pref., Japan
      • Kashiwagi Clinic
    • Chigasaki city, Kanagawa pref., Japan
      • Hayashi Diabetes Clinic
    • Hiratsuka city, Kanagawa pref., Japan
      • Takada Internal Medicine Clinic
    • Kamakura city, Kanagawa pref., Japan
      • Iroden Clinic
    • Kamakura city, Kanagawa pref., Japan
      • Nagasu Clinic
    • Odawara city, Kanagawa pref., Japan
      • Kobayashi Hospital
    • Sagamihara city, Kanagawa pref., Japan
      • Hakuai Iin
    • Sagamihara city, Kanagawa pref., Japan
      • Yamamoto Clinic
    • Yokohama city, Kanagawa pref., Japan
      • Kikuchi Clinic
    • Yokohama city, Kanagawa pref., Japan
      • Minamisawa Clinic
    • Yokohama city, Kanagawa pref., Japan
      • Shimokurata Heart Clinic
    • Yokohama city, Kanagawa pref., Japan
      • Yokohama Sotetsu Bldg. Clinic of Internal Medicine
    • Yokohama city, Kanagawa pref., Japan
      • Arima Clinic
    • Yokohama city, Kanagawa pref., Japan
      • Miho cho Cardiovascular Medical Clinic
  • Kumamoto pref.
    • Kumamoto city, Kumamoto pref., Japan
      • Jinnouchi Clinic Diabetes Care Center
    • Kumamoto city, Kumamoto pref., Japan
      • Maki Cardiovascular Clinic
    • Kumamoto city, Kumamoto pref., Japan
      • TERAO Hospital
    • Kumamoto city, Kumamoto pref., Japan
      • Munakata Clinic
    • Tamana city, Kumamoto pref., Japan
      • Higashi Diabetes and Cardiovascular Clinic
    • Tamana city, Kumamoto pref., Japan
      • Matsuo Clinic
    • Yatsushiro city, Kumamoto pref., Japan
      • Miyagi clinic cardiovascular medicine
  • Kyoto pref.
    • Kyotanabe city, Kyoto pref., Japan
      • Sawai Naika Iin
    • Kyoto city, Kyoto pref., Japan
      • Takenaka Clinic
    • Kyoto city, Kyoto pref., Japan
      • Tegoshi Clinic
    • Kyoto city, Kyoto pref., Japan
      • Asamoto Internal Medical Clinic
    • Kyoto city, Kyoto pref., Japan
      • Ijinkai Takeda General Hospital
    • Kyoto city, Kyoto pref., Japan
      • Koseikai Clinic
    • Kyoto city, Kyoto pref., Japan
      • Sakabe International Clinic
  • Mie pref.
    • Tsu city, Mie pref., Japan
      • Iwasaki Hospital
  • Miyazaki pref.
    • Miyazaki city, Miyazaki pref., Japan
      • Ishikawa Clinic
    • Miyazaki city, Miyazaki pref., Japan
      • Yokota Naika
    • Nichinan city, Miyazaki pref., Japan
      • Etou Clinic
    • Nichinan city, Miyazaki pref., Japan
      • Kawano Clinic
    • Nichinan city, Miyazaki pref., Japan
      • Yamaguchi Clinic
  • Nagano pref.
    • Nakano city, Nagano pref., Japan
      • Hasegawa Clinic
  • Nara pref.
    • Gojo city, Nara pref., Japan
      • Nara Prefectural Gojo Hospital
    • Kashihara city, Nara pref., Japan
      • Fujii Internal Medicine Clinic
    • Kita katsuragi gun, Nara pref., Japan
      • Matsuoka Clinic
    • Sakurai city, Nara pref., Japan
      • Ote Clinic of Internal
  • Niigata pref.
    • Joetsu city, Niigata pref., Japan
      • Uchiyama Clinic
    • Niigata city, Niigata pref., Japan
      • Maeda Medical Clinic
    • Niigata city, Niigata pref., Japan
      • Inoue Clinic
  • Osaka pref.
    • Fujiidera city, Osaka pref., Japan
      • Nishimura Clinic
    • Fujiidera city, Osaka pref., Japan
      • Shoseikai Matsuda Iin
    • Higashiosaka city, Osaka pref., Japan
      • Ikeda Clinic
    • Izumi city, Osaka pref., Japan
      • Kanazawa Clinic
    • Osaka city, Osaka pref., Japan
      • Kubota Clinic
    • Osaka city, Osaka pref., Japan
      • Fukuda Clinic
    • Osaka city, Osaka pref., Japan
      • Jikuhara Clinic
    • Osaka city, Osaka pref., Japan
      • Kawagishi-naika Clinic
    • Osaka city, Osaka pref., Japan
      • Kinugawa Cardiology Clinic
    • Osaka city, Osaka pref., Japan
      • Masaki Clinic
    • Osaka city, Osaka pref., Japan
      • Nanko Clinic
    • Osaka city, Osaka pref., Japan
      • Osaka Ekisaikai Hospital
    • Osaka city, Osaka pref., Japan
      • Tamatani Clinic
    • Sakai city, Osaka pref., Japan
      • Hayashi Clinic
    • Sakai city, Osaka pref., Japan
      • Nakao Medical Clinic
  • Saga pref.
    • Saga city, Saga pref., Japan
      • Saga Memorial Clinic
  • Saitama pref.
    • Ageo city, Saitama pref., Japan
      • Enomoto Clinic
    • Kawagoe city, Saitama pref., Japan
      • Asano Internal Medicine Clinic
    • Kawaguchi city, Saitama pref., Japan
      • Tokutake Iin
    • Kawaguchi city, Saitama pref., Japan
      • Iryohojin Hogi sinryojyo
    • Kumagaya city, Saitama pref., Japan
      • Medical Corporation Shibuya Clinic
    • Saitama city, Saitama pref., Japan
      • Tanaka Medical Clinic
  • Shizuoka pref.
    • Mishima city, Shizuoka pref., Japan
      • Yoshimura Eye&Internal Medical Clinic
    • Shizuoka city, Shizuoka pref., Japan
      • Shizuoka Municipal Hospital
  • Tochigi pref.
    • Tochigi city, Tochigi pref., Japan
      • Takada Clinic
  • Tokushima pref.
    • Anan city, Tokushima pref., Japan
      • Murakami Clinic
    • Awa city, Tokushima pref., Japan
      • Ota Clinic
    • Itano gun, Tokushima pref., Japan
      • Arizumi Clinic
    • Kaifu gun, Tokushima pref., Japan
      • Yuki National Health Insurance Hospital of Minami Town
    • Komatsushima city, Tokushima pref., Japan
      • Sekishinkan Hospital
    • Myozai gun, Tokushima pref., Japan
      • Iryohojin Tokujikai Tanaka Iin
    • Tokushima city, Tokushima pref., Japan
      • Kensei Uchimachi Clinic
    • Yoshinogawa city, Tokushima pref., Japan
      • Yata Clinic
  • Tokyo
    • Chuo ku, Tokyo, Japan
      • Tokyo Center Clinic
    • Katsushika ku, Tokyo, Japan
      • Okudo Poly Clinic
    • Nakano ku, Tokyo, Japan
      • Nakano Sunbright Clinic
    • Nerima ku, Tokyo, Japan
      • Sugawara Clinic
    • Setagaya ku, Tokyo, Japan
      • Tsurumachi Clinic
    • Shinjuku ku, Tokyo, Japan
      • Oda Clinic
    • Tachikawa city, Tokyo, Japan
      • Ishii Clinic
  • Yamaguchi pref.
    • Shimonoseki city, Yamaguchi pref., Japan
      • Ayame Medical Clinic
    • Shimonoseki city, Yamaguchi pref., Japan
      • Matsuda Medical Clinic
    • Shimonoseki city, Yamaguchi pref., Japan
      • Mizumachi Medical Clinic
  • Yamanashi pref.
    • Otsuki city, Yamanashi pref., Japan
      • Kuroda Iin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Hypercholesterolemia patients

   • Patients who have not achieved the target control levels of LDL-C in the "Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2007"

2. Type 2 diabetes patients

   • Patients diagnosed with type 2 diabetes and receiving diet therapy, exercise therapy, or medication
   • Patients who received constant therapy for three months before registration and have no plan for therapy change
   • Patients with kept HbA1c level (Japan Diabetes Society [JDS] level) of less than 7.0% (or, National Glycohemoglobin Standardization Program [NGSP] level of less than 7.4%) within three months before registration
   • Patients receiving or not receiving medication at present
3. Patients giving voluntary written consent to participate in the study
4. Male or female patients at 20 years or older

Exclusion Criteria:

1. Patients who administered rosuvastatin, atorvastatin or ezetimibe within three month at the registration
2. Patients with severe hypertension (systolic blood pressure [SBP] ≥ 180 mmHg or diastolic blood pressure [DBP] ≥ 110 mmHg)
3. Patients with type 1 diabetes
4. Patients judged to have familial hypercholesterolemia
5. Patients with a serum triglyceride level of ≥ 400 mg/dL
6. Patients who had the onset of cardiovascular or cerebrovascular disease within three months
7. Patients with serious heart failure (NYHA classification III - IV)
8. Patients with a history of hypersensitivity to statins
9. Patients with a history of drug-induced myopathy
10. Patients with severe complication of diabetes
11. Patients receiving insulin
12. Patients with serious liver or kidney disease
13. Patients with serious concurrent disease such as malignancy, or patients with severely limited lifespan
14. Patients who are or may be pregnant
15. Patients judged by the investigators to be ineligible for participation in the study for any other reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin administration group	Drug: Atorvastatin; Atorvastatin 10 mg (atorvastatin 10 mg tablet x 1 or atorvastatin 5 mg tablet x 2), orally,once daily for 12 months. (When not reach the LDL-C level of target in the Japan Atherosclerosis Society [JAS] Guidelines [GL] after 3 months, had the atorvastatin [ATV] dose of 20 mg.); Other Names: Lipitor
Experimental: Rosuvastatin administration group	Drug: Rosuvastatin; Rosuvastatin 5 mg (rosuvastatin 5 mg tablet x1 or rosuvastatin 2.5 mg tablet x 2), orally, once daily for 12 months. (When not reach the LDL-C level of target in JAS GL after 3 months, had the rosuvastatin [RSV] dose of 10 mg.); Other Names: Crestor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change in Non-high-density Lipoprotein Cholesterol (HDL-C) Level	Baseline, and 12 months after administration
Change in HbA1c Level	Baseline, 12 months after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Deterioration of Diabetic Treatment Status	"Deterioration of diabetic treatment status" is defined as addition of new drug, increase in dosage, drug changes (therapy intensification), and deterioration in HbA1c of > 0.5%.	Baseline, 12 months after administration
Number of Participants Stratified by Time to the Occurrence of Deterioration of Diabetic Treatment Status	"Deterioration of diabetic treatment status" is defined as addition of new drug, increase in dosage, drug changes (therapy intensification), and deterioration in HbA1c of > 0.5%.	Baseline, 3, 6, 12 months after administration
Percent Change in 1,5-AG Level	An inverse relationship exists between mean change in 1,5-AG level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa	Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status）
Change in HbA1c Level		Baseline, 3, 6 months after administration and the end of study treatment （or at the occurrence of deterioration of diabetic treatment status）
Percent Change in Blood Glucose Level (Fasting)		Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status）
Change in Blood Glucose Level (Fasting)		Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status）
Percent Change in Insulin Level	An inverse relationship exists between mean change in insulin level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa.	Baseline, 3, 6, 12 months after administration and the end of study treatment （or at the occurrence of deterioration of diabetic treatment status）
Change From Baseline in Insulin Level	An inverse relationship exists between mean change in insulin level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa	Baseline, 3, 6, 12 months after administration and the end of study treatment （or at the occurrence of deterioration of diabetic treatment status）
Frequency of Cardiovascular Events (Coronary Artery Disease, Heart Failure, Cerebrovascular Disease, Peripheral Artery Disease and Aortic Disease)		From the start of the treatment to the end of study treatment
Frequency of Serious Adverse Events (SAE)		Up to 12 months
Percent Changes in Lipids (LDL-C, HDL-C, TC, TG, Non-HDL-C/HDL-C Ratio, and FFA)		Baseline, 3, 6, 12 months after administration, the end of starting dose and the end of study treatment
Percent Change in Non-HDL-C Level		Baseline, 3 and 6 months after administration, the end of starting dose and the end of study treatment
Percent Changes in Lipids and Inflammatory Marker (Hs-CRP) and Their Correlation	Correlation between percent changes in lipids (LDL-C, HDL-C, non-HDL-C, TG, non-HDL-C/HDL-C ratio, LDL-C/HDL-C ratio, TC and FFA) and inflammatory marker (hs-CRP)	Baseline, 3, 6, 12 months after administration, the end of starting dose and the end of study treatment
Rate of Patients Who Have Reached the Target LDL-C Level Specified in Japan Atherosclerosis Society Guidelines (JASGL) 2007	Percentage of participants achieving the target LDL-C levels <100 mg/dL for participants with history of coronary artery diseases (CAD) and <120 mg/dL for participants without history of CAD are presented.	3 months after administration, the end of starting dose and the end of study treatment
Change From Baseline in 1,5-AG Level	An inverse relationship exists between mean change in 1,5-AG level and the mean rate of change when the degree of standard deviation is large, wherein the mean change is negative although the mean rate of change is positive or vice versa	Baseline, 3, 6, 12 months after administration and the end of study treatment（or at the occurrence of deterioration of diabetic treatment status）

Collaborators and Investigators

• Sponsor: Listen Trial Group
• Investigators: Study Chair: Hisao Ogawa, Ph.D, Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University

Publications and helpful links

General Publications

• Ogawa H, Matsui K, Saito Y, Sugiyama S, Jinnouchi H, Sugawara M, Masuda I, Mori H, Waki M, Yoshiyama M, Watada H. Differences between rosuvastatin and atorvastatin in lipid-lowering action and effect on glucose metabolism in Japanese hypercholesterolemic patients with concurrent diabetes. Lipid-lowering with highly potent statins in hyperlipidemia with type 2 diabetes patients (LISTEN) study -. Circ J. 2014;78(10):2512-5. doi: 10.1253/circj.cj-14-0810. Epub 2014 Sep 2.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: February 23, 2012
• First Submitted That Met QC Criteria: February 28, 2012
• First Posted (Estimate): March 5, 2012

Study Record Updates

• Last Update Posted (Estimate): March 17, 2015
• Last Update Submitted That Met QC Criteria: March 4, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium
• Other Study ID Numbers: 0059