Effect of tofogliflozin and pioglitazone on hepatic steatosis in NAFLD patients with type 2 diabetes.

JRCT ID: jRCTs031180159

Registered date:26/02/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Type 2 Diabetes, NAFLD
• Date of first enrollment: 23/02/2018
• Target sample size: 40
• Study type: Interventional

Intervention(s)

Arm A:Tofogliflozin 20mg <Time Frame: 0 to 24 weeks> , Tofogliflozin 20mg + Pioglitazone 15-30mg <Time Frame: 24 to 48 weeks>
Arm B: Pioglitazone 15-30mg <Time Frame: 0 to 24 weeks>, Tofoglifozin 20mg + Pioglitazone 15-30mg <Time Frame: 24 to 48 weeks>

Outcome(s)

• Primary Outcome: Change in liver fat content as measured by MRI-based proton density fat fraction (PDFF). <Time Frame: 24 weeks>

Secondary Outcome

1)Important secondary outcome
Change in serum ALT level. <Time Frame: 24 weeks>

2)other secondary outcomes
<1>
Secondary outcomes during randomization phase (mono-therapy), <Time Frame: 0 to 24 weeks >;
% change in liver fat by MRI-PDFF., >=10%, >=20% and >=30% reduction of MRI-PDFF., change in liver stiffness by MR elastography., >=5%, >=10% and >=15% reduction of liver stiffness., change in HbA1c, glucose, insulin, and HOMA-R., change in body weight and BMI., change in ALT, AST, gamma-GTP, ALP, total bilirubin and ALT/AST ratio., the proportion of normalization of ALT and AST level., platelet count, total protein albumin and choline esterase and ferritin., type IV collagen 7S, hsCRP, cytokeratin 18 fragment, adiponectin, ketone body fraction, M2BPG1, and urinary 8-OHdG., number(%) of adverse event.
<2>
Secondary outcomes during combination therapy phase <Time Frame: 24 to 48weeks>; liver fat content, liver stiffness, HbA1c, glucose, insulin, HOMA-R., body weight, BMI, ALT, AST, gamma-GTP, ALP, total bilirubin, ALT/AST ratio., the proportion of normalization of ALT and AST level, platelet count, total protein albumin and choline esterase, ferritin, type IV collagen 7S, hsCRP, cytokeratin 18 fragment, adiponectin, ketone body fraction, M2BPG1, urinary 8-OHdG., number(%) of adverse event.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 74age old
• Gender: Both

Include criteria

<1>Inclusion criteria for study entry;
1. men and women, aged 20-74 years.
2. Type 2 diabetic patients who have been treated with diet/exercise therapy.
3. HbA1c higher than 6.5% (measured within 90 days before study registration).
4. Clinically diagnosed NAFLD
5. ALT higher than the upper limited normal (measured within 90 days before study registration).
6. Patients who provide written consent to participate in the trial of their own free will.
<2>Inclusion criteria for randomization;
Patients with screening MRI-PDFF >= 10% steatosis.

Exclude criteria

1. Alcohol consumption greater than 30g/day ethanol for males or 20g/day ethanol for females.
2. Patients diagnosed viral hepatitis.
3. Other causes of liver disease including autoimmune and drug -induced hepatic injury.
4. Patients diagnosed hepatic cirrhosis or serious hepatic dysfunction (Child-Pugh B and C).
5. Platelet count < 150,000/mm3 (measured within 90 days before study registration).
6. BMI < 22 kg/m2 (measured within 90 days before study registration).
7. ALT >= 5 times higher than the upper limited normal (measured within 90 days before study registration)
8. Serious renal dysfunction or eGFR < 60 mL /min/1.73 m2 (measured within 90 days before study registration).
9. Type 1 diabetes or HbA1c >= 9.0% (measured within 90 days before study registration)
10. Patients using SGLT2 inhibitors, pioglitazone, insulin or GLP-1 agonists.
11. Patients taking vitamin E.
12. Contraindications to the MRI (for example, patients using heart pacemaker).
13. Patients who can not undergo MRI (for example, patients who can not hold breath long enough or patients with iron overload).
14. Heart failure (NYHA III or more)
15. Patients with cancer or history of cancer in previous 5 years.
16. Severe ketosis, diabetic coma or precoma.
17. Sever infection, within one week before or after the surgery, sever injury.
18. History of hypersensitivity to any of the ingredients of the study drug.
19. Pregnant women, women suspected of being pregnant.
20. Lactating women or patients who can not prevent conception during study period.
21. Patients who are ineligible in the opinion of the investigator.

Related Information

• Primary Sponsor: Yoneda Masato
• Secondary Sponsor: Nakajima Atsushi
• Source(s) of Monetary Support: Kowa Company, Ltd., Kowa Pharmaceutical Co. Ltd
• Secondary ID(s): UMIN000030355