To Evaluate the Effect of Nesinaact on Non-alcoholic Steatohepatitis Through MRI and Liver Fibroscan in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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This study was designed to evaluate the effect of Nesinaact on non-alcoholic steatohepatitis through magnetic resonance imaging (MRI)-based proton density-fat fraction (MRI-PDFF) and liver fibroscan in patients with type 2 diabetes. This is a prospective, open-label, single-arm, single-center clinical Study. After 24 weeks of Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment, the improvement of parameters estimated by MRI and liver fibroscan will be estimated.

Official Title
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To Evaluate the Effect of Nesinaact on Non-alcoholic Steatohepatitis Through MRI and Liver Fibroscan in Patients With Type 2 Diabetes: A Prospective, Open-Label, Single-Arm, Single-Center Clinical Study

Conditions
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Non-alcoholic Steatohepatitis, Type2 Diabetes

Intervention / Treatment
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* Drug: Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment for 24 weeks


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients ages >= 20 years Patients diagnosed with non-alcoholic fatty liver disease (NAFLD). => Definition of NAFLD: CAP (Controlled attenuation parameter) >= 250 dB/m Diabetic patients who meet one of the following glycemic conditions: Patients with glycated hemoglobin (HbA1c) ranging 6.5 8.5 % while not taking an antidiabetic for more than 12 weeks irrespective of duration of diabetes. Patients with HbA1c ranging 6.5 9.0 % in screening while using metformin monotherapy for more than 8 weeks without changing the dose irrespective of duration of diabetes. Exclusion Criteria: Patients who meet the criteria for alcoholic liver disease whose alcohol intake for the recent tow years if above 210 g per week in men and above 140 g per week in women) Patients with chronic hepatitis B, C, or type 1 diabetes, or secondary diabetes Patients with history of acute or chronic metabolic acidosis and ketoacidosis, including diabetic ketoacidosis accompanied or not accompanied by coma Patients who were administered an oral hypoglycemic agent or insulin other than metformin within 8 weeks prior ro screening, or are likely to be administered it during the study duration among patients receiving monotherapy. Patients who had hypersensitivity to biguanide or glitazone in the past. Patients who received oral or parenteral corticosteroid treatment chronically (for more than 14 consecutive days) within 8 weeks prior to screening Patients wih past history of lactic acidosis Patients with a genetic disorder, such as galactose intolerance, Lapp lactase deficiency or glucose-galactose impaired absorption, etc. Patients wih malnutrition, starvation, weakness, (Including patients with severe infection), pituitary insufficiency or adrenal insufficiency Patients who have been receiving radiotherapy or chemotherapy due to bladder cancer and other malignant tumor, or it is less than 2 years since the patients received it. Patients with past history of bladder cancer A patient with history of drug abuse or alcoholism in 12 weeks A patient who has hear failure (NYHA class 3 4) or uncontrolled arrhythmia within 6 months A patient who has acute cardiovascular disease within 12 weeks (including unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular disease, coronary artery bypass, or coronary intervention) A person who falls under one of the followings: 1) A patient with serum creatinine level >= 1.5 mg/dL in men and 1.4 mg/dL in women or a patient wih moderate to severe renal impairment (creatinine clearance: < 50 ml/min) 2) An anemia patient with 10.5 g/dL of Hb level A pregnant or nursing woman A patient who does not consent to use a proper method of contraception during the study period only among women or men of childbearing age A patient who has taken investigational drug in other clinical study within 4 weeks following informed consent A person who may not participate in the study according to investigator's judgement A person who cannot read the informed consent form (e.g: an illiterate, a foreigner, etc.)

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment
Interventional Model Description: This is a prospective, open-label, single-arm, single-center clinical Study. All participants will be treated with Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) for 24 weeks.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment for 24 weeks | Drug: Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment for 24 weeks<br>* All participants will be treated with Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) for 24 weeks. Patients who have not been prescribed any other anti-diabetic drugs at least for 12 weeks and whose HbA1c ranges from 6.5 8.5%, can be enrolled. If Patients has been prescribed metformin as monotherapy, they have to substitute metformin with nesinaact 25-15 for enrollment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A degree of liver steatosis | Magnetic resonance imaging (MRI)-based proton density-fat fraction (MRI-PDFF) will be evaluated to confirm the improvement in liver steatosis. | 24 weeks after starting Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment | 
| A degree of liver fibrosis | In liver fibroscan, liver stiffness (kPa) as a marker of fibrosis and CAP (dB/m) as a marker of steatosis will be estimated. | 24 weeks after starting Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical glucometabolic parameters : HbA1c | HbA1c in % | 24 weeks after starting Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment | 
| Clinical glucometabolic parameters : Lipid parameters | Total cholesterol in mg/dL | 24 weeks after starting Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment | 
| Clinical glucometabolic parameters : Lipid parameters | Triglyceride in mg/dL | 24 weeks after starting Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment | 
| Clinical glucometabolic parameters : Lipid parameters | HDL-cholesterol in mg/dL | 24 weeks after starting Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment | 
| Clinical glucometabolic parameters : Lipid parameters | LDL-cholesterol in mg/dL | 24 weeks after starting Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment | 
| Clinical glucometabolic parameters : Liver enzymes | AST in IU/L | 24 weeks after starting Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment | 
| Clinical glucometabolic parameters : Liver enzymes | ALT in IU/L | 24 weeks after starting Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment | 
| Clinical glucometabolic parameters :Anthropometric parameters | Blood pressure in mmHg | 24 weeks after starting Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment | 
| Clinical glucometabolic parameters :Anthropometric parameters | Body weight in kilogram | 24 weeks after starting Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment | 
| Clinical glucometabolic parameters :Anthropometric parameters | Body mass idex in kg/m2 | 24 weeks after starting Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment |