- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02330406
Randomized Evaluation of Anagliptin Versus Sitagliptin On Low-density lipoproteiN Cholesterol in Diabetes Trial (REASON)
August 22, 2019 updated by: Institute for Clinical Effectiveness, Japan
Effect of Anagliptin and Sitagliptin on Low-density Lipoprotein Cholesterol in Patients With Type 2 Diabetes and Cardiovascular Risk Factors: Randomized Controlled Trial
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
353
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Okinawa
-
Tomishiro, Okinawa, Japan, 901-0243
- Department of Cardiovascular Medicine, Tomishiro Central Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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:
- 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
- Presence of stenosis (>=25%) or plaque on the previous coronary angiography or coronary CT
- Presence of coronary calcification on the previous coronary CT
- History of acute coronary syndrome
- History of percutaneous coronary intervention or coronary artery bypass graft
- History of stroke (ischemic stroke or hemorrhagic stroke)
- History of transient ischemic attack
- History of peripheral artery diseases or aortic disorders
- Ankle-Brachial Index (AMI) equal to or less than 0.9 in the past measurement
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Anagliptin
Anagliptin 100 mg bid for 52 weeks.
Can increase to 200 mg bid if needed.
|
Suiny 100 mg
Other Names:
|
Active Comparator: Sitagliptin
Sitagliptin 50 mg qd for 52 weeks.
Can increase to 100 mg qd if needed
|
Januvia 50 mg Glactiv 50 mg
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in low-density lipoprotein cholesterol
Time Frame: 52-weeks
|
52-weeks
|
Change in glycated hemoglobin
Time Frame: 52-weeks
|
52-weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in fasting glucose
Time Frame: 52-weeks
|
52-weeks
|
Change in fasting insulin
Time Frame: 52-weeks
|
52-weeks
|
Change in 1.5-Anhydro-D-glucitol
Time Frame: 52-weeks
|
52-weeks
|
Change in C peptide
Time Frame: 52-weeks
|
52-weeks
|
Change in total cholesterol, triglyceride, non high dencisty lipoprotein cholesterol
Time Frame: 52-weeks
|
52-weeks
|
Change in Apolipoprotein A1, Apolipoprotein B, Apolipoprotein E
Time Frame: 52-weeks
|
52-weeks
|
Change in Apolipoprotein B48
Time Frame: 52-weeks
|
52-weeks
|
Change in small dense low density lipoprotein
Time Frame: 52-weeks
|
52-weeks
|
Change in high sensitivity C-reactive protein
Time Frame: 52-weeks
|
52-weeks
|
Change in interleukin-6
Time Frame: 52-weeks
|
52-weeks
|
Change in cholesterol absorption marker (campesterol; sitosterol)
Time Frame: 52-weeks
|
52-weeks
|
Change in cholesterol synthesis marker (lathosterol)
Time Frame: 52-weeks
|
52-weeks
|
Change in high molecular weight adiponectin
Time Frame: 52-weeks
|
52-weeks
|
Change in ratio of albumin and creatinine in urine
Time Frame: 52-weeks
|
52-weeks
|
Progression, unchange, remission rate of microalbumin and macroalbumin in urine
Time Frame: 52-weeks
|
52-weeks
|
Change in estimated glomerular filtration rate
Time Frame: 52-weeks
|
52-weeks
|
Change in glycated hemoglobin stratified by body mass index and waist circumference
Time Frame: 52-weeks
|
52-weeks
|
Correlation between glycated hemoglobin and body mass index or waist circumference
Time Frame: 52-weeks
|
52-weeks
|
Change in intima-media thickness or flow mediated dilation
Time Frame: 52-weeks
|
52-weeks
|
Change in postprandial glucose, insulin and activated glucagon-like peptide-1
Time Frame: 52-weeks
|
52-weeks
|
Change in lipid profile and molecular size measured
Time Frame: 52-weeks
|
52-weeks
|
Change in fatty acid fraction
Time Frame: 52-weeks
|
52-weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Shinichiro Ueda, MD, PhD, Professor of Medicine, Department of Clinical Pharmacology & Therapeutics, University of the Ryukyus
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Furuhashi M, Sakuma I, Morimoto T, Higashiura Y, Sakai A, Matsumoto M, Sakuma M, Shimabukuro M, Nomiyama T, Arasaki O, Node K, Ueda S. Treatment with anagliptin, a DPP-4 inhibitor, decreases FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular disease who are receiving statin therapy. Cardiovasc Diabetol. 2020 Jun 15;19(1):89. doi: 10.1186/s12933-020-01061-0.
- Chihara A, Tanaka A, Morimoto T, Sakuma M, Shimabukuro M, Nomiyama T, Arasaki O, Ueda S, Node K. Differences in lipid metabolism between anagliptin and sitagliptin in patients with type 2 diabetes on statin therapy: a secondary analysis of the REASON trial. Cardiovasc Diabetol. 2019 Nov 16;18(1):158. doi: 10.1186/s12933-019-0965-3.
- Morimoto T, Sakuma I, Sakuma M, Tokushige A, Natsuaki M, Asahi T, Shimabukuro M, Nomiyama T, Arasaki O, Node K, Ueda S. Randomized Evaluation of Anagliptin vs Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) Trial: A 52-week, open-label, randomized clinical trial. Sci Rep. 2019 Jun 12;9(1):8537. doi: 10.1038/s41598-019-44885-x. Erratum In: Sci Rep. 2020 Feb 21;10(1):3548.
- Ueda S, Shimabukuro M, Arasaki O, Node K, Nomiyama T, Morimoto T. Effect of Anagliptin and Sitagliptin on Low-Density Lipoprotein Cholesterol in Type 2 Diabetic Patients with Dyslipidemia and Cardiovascular Risk: Rationale and Study Design of the REASON Trial. Cardiovasc Drugs Ther. 2018 Feb;32(1):73-80. doi: 10.1007/s10557-018-6776-z.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 1, 2015
Primary Completion (Actual)
January 1, 2018
Study Completion (Actual)
March 1, 2019
Study Registration Dates
First Submitted
December 30, 2014
First Submitted That Met QC Criteria
December 30, 2014
First Posted (Estimate)
January 5, 2015
Study Record Updates
Last Update Posted (Actual)
August 28, 2019
Last Update Submitted That Met QC Criteria
August 22, 2019
Last Verified
August 1, 2019
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Myocardial Ischemia
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Glucose Metabolism Disorders
- Metabolic Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Endocrine System Diseases
- Coronary Artery Disease
- Coronary Disease
- Diabetes Mellitus
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Protease Inhibitors
- Incretins
- Dipeptidyl-Peptidase IV Inhibitors
- Sitagliptin Phosphate
- Anagliptin
Other Study ID Numbers
- ICE_2014_01R
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Coronary Disease
-
Peking Union Medical College HospitalNot yet recruitingCoronary Artery Disease | Inflammation | Coronary Artery Disease Progression | Coronary Artery Stenosis | Coronary Artery Restenosis | Inflammatory Disease | Inflammation VascularChina
-
Peking Union Medical College HospitalRecruitingCoronary Artery Disease | Inflammation | Coronary Artery Disease Progression | Coronary Artery Stenosis | Coronary Artery Restenosis | Inflammatory Disease | Inflammation VascularChina
-
Fundación EPICActive, not recruitingCoronary Artery Disease | Left Main Coronary Artery Disease | Left Main Coronary Artery Stenosis | Restenosis, CoronarySpain
-
Peking University Third HospitalCompletedCoronary Microvascular Dysfunction | Obstructive Coronary Heart DiseaseChina
-
Seung-Jung ParkCardioVascular Research Foundation, KoreaRecruitingCoronary Stenosis | Coronary Artery Bypass Grafting | Coronary Artery Disease Progression | Percutaneous Coronary RevascularizationKorea, Republic of
-
Istanbul UniversityCompletedIschemic Heart Disease | Coronary Microvascular Disease | Microvascular Angina | Coronary Microvascular Dysfunction | Non-Obstructive Coronary Atherosclerosis | Microvascular Coronary Artery DiseaseTurkey
-
Centro de estudios en Cardiologia IntervencionistaCompletedCoronary Heart Disease | Coronary RestenosisArgentina
-
Deutsches Herzzentrum MuenchenCompletedCoronary Heart DiseaseGermany
-
Fundación EPICRecruitingCoronary Artery Disease | Coronary Disease | Coronary Occlusion | Left Main Coronary Artery Disease | Coronary Artery StenosisSpain
-
Medical University of SilesiaCompletedLeft Main Coronary Artery Disease | Restenosis, Coronary | PTCA Left Main Artery ComplicationsPoland, Italy
Clinical Trials on Anagliptin
-
JW PharmaceuticalCompletedType 2 Diabetes MellitusKorea, Republic of
-
JW PharmaceuticalCompletedType 2 DiabetesKorea, Republic of
-
JW PharmaceuticalActive, not recruitingType 2 Diabetes MellitusKorea, Republic of
-
JW PharmaceuticalCompletedType 2 Diabetes MellitusKorea, Republic of