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Randomized Evaluation of Anagliptin Versus Sitagliptin On Low-density lipoproteiN Cholesterol in Diabetes Trial (REASON)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02330406
Recruitment Status : Completed
First Posted : January 5, 2015
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
Institute for Clinical Effectiveness, Japan

Brief Summary:
The purpose of this study is to determine whether Anagliptin or Sitagliptin are effective in reducing the low-density lipoprotein cholesterol in patients with type 2 diabetes and cardiovascular risk factors on statin.

Condition or disease Intervention/treatment Phase
Dipeptidyl-Peptidase 4 Inhibitors LDL Cholesterol Glycosylated Hemoglobin Diabetes Mellitus Coronary Disease Drug: Anagliptin Drug: Sitagliptin Phase 4

Detailed Description:
Diabetes is a significant cause of cardiovascular and cerebrovascular events. Especially, diabetic patients with cardiovascular risk factors were significantly higher risk for cardiovascular and cerebrovasculara event. Therefore, several medical management strategies including anti-diabetic medications and statins were considered for those patients. However, in spite of such treatment, still many patients have cardiovascular and cerebrovascular events. One of the hypothesis is the residual risk such as elevated low-density lipoprotein cholesterol (LDLC) even with statin therapy. Anagliptin, one of the dipeptidyl peptidase-4 (DPP4) inhibiors, was reported to reduce LDLC and may have pontential to decrease the cardiovascular and cerebrovascular risk for such patients on statins. We, thus, conduct a randomized controlled trial to compare Anagliptin or Sitagliptin in terms of change of LDLC for 52 weeks as well as glycemic control.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 353 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Anagliptin and Sitagliptin on Low-density Lipoprotein Cholesterol in Patients With Type 2 Diabetes and Cardiovascular Risk Factors: Randomized Controlled Trial
Actual Study Start Date : April 2015
Actual Primary Completion Date : January 2018
Actual Study Completion Date : March 2019


Arm Intervention/treatment
Active Comparator: Anagliptin
Anagliptin 100 mg bid for 52 weeks. Can increase to 200 mg bid if needed.
Drug: Anagliptin
Suiny 100 mg
Other Name: Suiny

Active Comparator: Sitagliptin
Sitagliptin 50 mg qd for 52 weeks. Can increase to 100 mg qd if needed
Drug: Sitagliptin
Januvia 50 mg Glactiv 50 mg
Other Names:
  • Januvia
  • Glactiv




Primary Outcome Measures :
  1. Change in low-density lipoprotein cholesterol [ Time Frame: 52-weeks ]
  2. Change in glycated hemoglobin [ Time Frame: 52-weeks ]

Secondary Outcome Measures :
  1. Change in fasting glucose [ Time Frame: 52-weeks ]
  2. Change in fasting insulin [ Time Frame: 52-weeks ]
  3. Change in 1.5-Anhydro-D-glucitol [ Time Frame: 52-weeks ]
  4. Change in C peptide [ Time Frame: 52-weeks ]
  5. Change in total cholesterol, triglyceride, non high dencisty lipoprotein cholesterol [ Time Frame: 52-weeks ]
  6. Change in Apolipoprotein A1, Apolipoprotein B, Apolipoprotein E [ Time Frame: 52-weeks ]
  7. Change in Apolipoprotein B48 [ Time Frame: 52-weeks ]
  8. Change in small dense low density lipoprotein [ Time Frame: 52-weeks ]
  9. Change in high sensitivity C-reactive protein [ Time Frame: 52-weeks ]
  10. Change in interleukin-6 [ Time Frame: 52-weeks ]
  11. Change in cholesterol absorption marker (campesterol; sitosterol) [ Time Frame: 52-weeks ]
  12. Change in cholesterol synthesis marker (lathosterol) [ Time Frame: 52-weeks ]
  13. Change in high molecular weight adiponectin [ Time Frame: 52-weeks ]
  14. Change in ratio of albumin and creatinine in urine [ Time Frame: 52-weeks ]
  15. Progression, unchange, remission rate of microalbumin and macroalbumin in urine [ Time Frame: 52-weeks ]
  16. Change in estimated glomerular filtration rate [ Time Frame: 52-weeks ]
  17. Change in glycated hemoglobin stratified by body mass index and waist circumference [ Time Frame: 52-weeks ]
  18. Correlation between glycated hemoglobin and body mass index or waist circumference [ Time Frame: 52-weeks ]
  19. Change in intima-media thickness or flow mediated dilation [ Time Frame: 52-weeks ]
  20. Change in postprandial glucose, insulin and activated glucagon-like peptide-1 [ Time Frame: 52-weeks ]
  21. Change in lipid profile and molecular size measured [ Time Frame: 52-weeks ]
  22. Change in fatty acid fraction [ Time Frame: 52-weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with type 2 diabetes with cardiovascular risk factors (*) who treated with diet, exercise or antidiabetic medications
  • Patients who were treated with statins for 8 weeks or longer
  • Patients with low-density lipoprotein cholesterol equal to or greater than 100 mg/dL in the at least one of three measurements after the administration of statins
  • Patients with glycerated hemoglobin (HbA1c, NGSP) equal to or greater than 6.0 % (7.0 % if patients were not treated with dipeptidyl-peptidase 4 inhibitors) and lesser than 10.5 %

(*) cardiovascular risk factors were any of following conditions

  1. Presence of stenosis (>=25%) or plaque on the previous coronary angiography or coronary CT
  2. Presence of coronary calcification on the previous coronary CT
  3. History of acute coronary syndrome
  4. History of percutaneous coronary intervention or coronary artery bypass graft
  5. History of stroke (ischemic stroke or hemorrhagic stroke)
  6. History of transient ischemic attack
  7. History of peripheral artery diseases or aortic disorders
  8. Ankle-Brachial Index (AMI) equal to or less than 0.9 in the past measurement
  9. Presence of carotid artery plaque (including Max IMT >=1.1mm) on carotid ultrasonography in the past

Exclusion Criteria:

  • Patients with type 1 diabetes
  • Patients with triglyceride equal to or greater than 400 mg/dL in the previous fasting measurements
  • Patients with pregnancy, possible pregnancy, or on breast-feeding
  • Patients with severe infections, perioperative status, or severe trauma
  • Patients with renal dysfunction (creatinine >= 2.4 mg/dl for men, >= 2.0 mg/dl for women)
  • Patients who were received glucagon-like peptide-1receptor agonists
  • Patients whom physician in charge considered inappropriate for the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02330406


Locations
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Japan
Department of Cardiovascular Medicine, Tomishiro Central Hospital
Tomishiro, Okinawa, Japan, 901-0243
Sponsors and Collaborators
Institute for Clinical Effectiveness, Japan
Investigators
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Principal Investigator: Shinichiro Ueda, MD, PhD Professor of Medicine, Department of Clinical Pharmacology & Therapeutics, University of the Ryukyus

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Institute for Clinical Effectiveness, Japan
ClinicalTrials.gov Identifier: NCT02330406    
Other Study ID Numbers: ICE_2014_01R
First Posted: January 5, 2015    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Institute for Clinical Effectiveness, Japan:
Dipeptidyl-Peptidase 4 Inhibitors
LDL Cholesterol
Glycosylated Hemoglobin
Diabetes Mellitus
Coronary Disease
Additional relevant MeSH terms:
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Coronary Disease
Coronary Artery Disease
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Sitagliptin Phosphate
Anagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action