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

Sponsor

Yonsei University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03950505

Collaborator

(none)

Enrollment

Location

Arm

6.1

Anticipated Duration (Months)

9.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non-alcoholic Steatohepatitis Type2 Diabetes	Drug: Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment for 24 weeks	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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.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)

Masking Description:

No masking is applied, as this is an open label study

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 29, 2020

Anticipated Primary Completion Date :

Dec 1, 2020

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 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 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.

Arm

Intervention/Treatment

Experimental: 1

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

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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.)