Effect of Fimasartan on Extended RAS and Vascular Functions in Patients With Type 2 Diabetes and Hypertension

Study Overview
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Brief Summary
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In this study, we will assess the change of extended renin-angiotensin system including serum ACE-2 and angiotensin(1-7) levels and subclinical atherosclerosis after using fimasartan (an ARB), compared to amlodipine in hypertensive patients with T2DM.

Detailed Description
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Several clinical trials aimed at studying the benefits of RAS blockade in the diabetic complications. HOPE, RENAAL, IRMA2, IDNT, ONTARGET studies proved that ACE inhibitors or ARBs reduced the risk of diabetic complications. Recent studies proved that fimasartan, one of the ARBs, stabilizes the activity of renin-angiotensin system. However, understanding the change in concentration of serum ACE, ACE-2, angiotensin(1-7), and angiotensin-II should help clinicians select more appropriate drug between ACE inhibitors and ARBs with clear evidence. Moreover, since RAS antagonists are the first-line drugs for antihypertensive therapy in patients with T2DM, it is meaningful to understand the change of RAS-related factors in serum after using the drugs.

Official Title
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Effect of Fimasartan or Amlodipine on Extended Renin-angiotensin System in Patients With Type 2 Diabetes and Hypertension

Conditions
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Hypertension, Atherosclerosis, Diabetes Mellitus, Type 2, Renin Hypertension

Intervention / Treatment
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* Drug: Fimasartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 30 years old Type 2 diabetes by American Diabetes Association criteria HbA1c: 6.5% ≤ - < 10.0% Systolic blood pressure: 140 ≤ - < 180 mmHg or Diastolic blood pressure: 85 ≤ - < 110 mmHg Statin (-) or no change in low to moderate intensity statin [14] dose in recent 3 months Exclusion Criteria: Contraindication of fimasartan or amlodipine History of RAS inhibitors (ACE inhibitors or ARBs) or calcium channel blockers in the previous 3 months Pregnant women, women with potential of pregnancy not using adequate contraception method as evaluated by the investigator, lactating women Type 1 diabetes or diabetes secondary to chronic pancreatitis or to pancreatectomy Confirmed cardiovascular disease (acute coronary syndrome, stroke, or transient ischemic attack) within 3 months of screening Chronic hepatitis B or C (except healthy carrier of HBV), liver disease (AST/ALT > 3-fold the upper limit of normal) Chronic kidney disease (serum creatinine > 2.0 mg/dL) Hyperkalemia serum potassium >5.0 mEq/L Any previous cancer within 5 years (except squamous cell cancer, cervical cancer, thyroid cancer with appropriate treatment) except thyroid cancer or carcinoma in situ

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fimasartan<br>- Fimasartan group: Fimasartan, 60 mg once a day, oral administration | Drug: Fimasartan<br>* - Fimasartan group: fimasartan, 60 mg once a day, oral administration<br>* Other names: Kanarb;|
| Active Comparator: Amlodipine<br>- Comparator group: Amlodipine, 5 mg once a day, oral administration | Drug: Fimasartan<br>* - Fimasartan group: fimasartan, 60 mg once a day, oral administration<br>* Other names: Kanarb;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Angiotensin(1-7) | Changes of serum angiotensin(1-7) at week 12 from baseline | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | Change in blood pressure from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24 | 12 weeks | 
| ACE-2 | Change in ACE-2 from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24 | 12 weeks | 
| ACE | Change in ACE from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24 | 12 weeks | 
| Renin | Change in renin from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24 | 12 weeks | 
| angiotensin | Change in angiotensin from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24 | 12 weeks | 
| atherosclerosis | Change in atherosclerosis from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24 | 12 weeks | 
| Muscle mass | Change in muscle mass from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24 | 12 weeks | 
| Fat mass | Change in fat mass from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24 | 12 weeks | 
| HbA1c | Change in HbA1c from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24 | 12 weeks |