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

Phase 4

• Conditions: Non-alcoholic Steatohepatitis; Type2 Diabetes
• Interventions: Drug: Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment for 24 weeks

• Registration Number: NCT03950505
• Lead Sponsor: Yonsei University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-05-08
• Study First Submitted QC: 2019-05-13
• Study First Posted: 2019-05-15
• Study Start: 2020-05-29
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-08
• Last Update Posted: 2020-10-09
• Primary Completion: 2020-12
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Male or female patients ages >= 20 years

2. Patients diagnosed with non-alcoholic fatty liver disease (NAFLD).

   => Definition of NAFLD: CAP (Controlled attenuation parameter) >= 250 dB/m

3. 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

1. 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)
2. Patients with chronic hepatitis B, C, or type 1 diabetes, or secondary diabetes
3. Patients with history of acute or chronic metabolic acidosis and ketoacidosis, including diabetic ketoacidosis accompanied or not accompanied by coma
4. 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.
5. Patients who had hypersensitivity to biguanide or glitazone in the past.
6. Patients who received oral or parenteral corticosteroid treatment chronically (for more than 14 consecutive days) within 8 weeks prior to screening
7. Patients wih past history of lactic acidosis
8. Patients with a genetic disorder, such as galactose intolerance, Lapp lactase deficiency or glucose-galactose impaired absorption, etc.
9. Patients wih malnutrition, starvation, weakness, (Including patients with severe infection), pituitary insufficiency or adrenal insufficiency
10. 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.
11. Patients with past history of bladder cancer
12. A patient with history of drug abuse or alcoholism in 12 weeks
13. A patient who has hear failure (NYHA class 3~4) or uncontrolled arrhythmia within 6 months
14. 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)
15. 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.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment for 24 weeks	Nesinaact 25/15 (Alogliptin benzoate 25mg, pioglitazone hydrochloride 15mg) treatment for 24 weeks

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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	LDL-cholesterol in mg/dL
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	Body mass idex in kg/m2

Trial Locations

Locations (1)

Division of Geriatrics, Department of Internal Medicine, Yonsei University College of Medicine; 🇰🇷 Seoul, Korea, Republic of