Effect of Erugliflozin On Liver Fat, Liver Fibrosis and Glycemic Control in Type II DM Patients With NASH/NAFLD

Liver Fibrosis Clinical Trial

— Ertu-NASH  

Official title:

Effects of Ertugliflozin on Liver Fat, Liver Fibrosis & Glycemic Control in Subjects With Type 2 Diabetes Mellitus (T2DM) & Non-Alcoholic Fatty Liver Disease /Non-Alcoholic Steatohepatitis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05644717
• Other study ID #: GTZ_DM_007_22
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: March 1, 2023
• Est. completion date: March 1, 2024

Study information

• Verified date: November 2022
• Source: Getz Pharma
• Contact: Atiba Alvi, MBBS
• Phone: 03203200222
• Email: atiba.alvi[@]getzpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open-label, prospective, single-arm, multicenter study to determine effects of Ertugliflozin on liver fat, liver fibrosis & glycemic control in subjects with Type 2 Diabetes Mellitus (T2DM) with Non-Alcoholic Fatty Liver Disease (NAFLD)/Non-Alcoholic Steatohepatitis (NASH)

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 164
• Est. completion date: March 1, 2024
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patient able to provide written informed consent
• Adult males & females between 18 to 65 years
• SGLT2i and insulin naïve patients
• BMI >23 Kg/m2
• HbA1C % = 6.5 to 10
• Documented hepatic steatosis or fatty liver disease on Ultrasound
• Patient with Type II Diabetes Mellitus

Exclusion Criteria:

• History of use of SGLT 2 inhibitors or Glucagon-like peptide (GLP) 1 agonist or insulin; 3 months prior to enrollment in the study.
• Pioglitazone use in the past 6 months
• History of vitamin E use (400mg twice daily) 3 months prior to enrollment in the study.
• History of anti-obesity medication or weight loss procedure (bariatric surgery) use within 3 months prior to enrollment in the study.
• History of uncontrolled Endocrine disorder (for example uncontrolled hypothyroidism, or that requires frequent dose adjustment, or Cushing's syndrome)
• History of liver disease including viral hepatitis, auto-immune hepatitis, liver cirrhosis, hepatocellular carcinoma and/or HIV
• History of recurrent UTIs and mycotic infection.
• Severely ill patients (who have high grade fever, sepsis or acute infection)
• Pregnant woman, lactating woman or planning pregnancy during study duration
• History of Drug-induced liver disease (e.g. amiodarone, valproate, tamoxifen, methotrexate, steroids (including homeopathic medicines).
• History of active substance abuse (cannabinoid-derived substances like heroin, cocaine, amphetamines) based on history and/or laboratory tests
• Alcohol intake 10 - 30 g/day (three drinks per day) within the previous year
• Active substance abuse such as acetaminophen over-use, hashish, tobacco products, heroin, cocaine or amphetamines.
• Severe hepatic impairment ( AST & ALT levels > 3 times upper limit normal

Related Conditions & MeSH terms

• Body Weight
• Body Weight Changes
• Fibrosis
• Glycemic Control
• Liver Cirrhosis
• Liver Fat
• Liver Fibrosis
• Tolerance

Intervention

Drug:
• Ertugliflozin 5 mg, 15mg
Ertugliflozin 5/15mg once daily in addition to standard of care

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Getz Pharma

References & Publications (6)

Gusdon AM, Song KX, Qu S. Nonalcoholic Fatty liver disease: pathogenesis and therapeutics from a mitochondria-centric perspective. Oxid Med Cell Longev. 2014;2014:637027. doi: 10.1155/2014/637027. Epub 2014 Oct 13. — View Citation

Hu M, Phan F, Bourron O, Ferre P, Foufelle F. Steatosis and NASH in type 2 diabetes. Biochimie. 2017 Dec;143:37-41. doi: 10.1016/j.biochi.2017.10.019. Epub 2017 Oct 31. — View Citation

Mantovani A, Byrne CD, Bonora E, Targher G. Nonalcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: A Meta-analysis. Diabetes Care. 2018 Feb;41(2):372-382. doi: 10.2337/dc17-1902. — View Citation

Mantovani A, Zaza G, Byrne CD, Lonardo A, Zoppini G, Bonora E, Targher G. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis. Metabolism. 2018 Feb;79:64-76. doi: 10.1016/j.metabol.2017.11.003. Epub 2017 Nov 11. — View Citation

Schuppan D, Schattenberg JM. Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches. J Gastroenterol Hepatol. 2013 Aug;28 Suppl 1:68-76. doi: 10.1111/jgh.12212. — View Citation

Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. J Hepatol. 2016 Sep;65(3):589-600. doi: 10.1016/j.jhep.2016.05.013. Epub 2016 May 17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiologic liver parameters	Number of participants reported change in liver fat content from baseline, as quantified by fibroscan	up to 24 weeks
Secondary	HbA1c% levels compare with baseline in 6 months	Efficacy	up to 24 weeks
Secondary	Change in body weight compare with baseline in 6 months	Body Weight	up to 24 weeks
Secondary	Change in waist circumference compare with baseline in 6 months	Waist Circumference	up to 24 weeks
Secondary	Fibrosis 4 score levels compare with baseline in 6 months	Fibrosis Scoring < 1.45 indicates Fibrosis Stage 0-2, 1.45 to 3.25 is deemed indeterminate fibrosis stage, > 3.25 indicates Fibrosis stage 3-4	up to 24 weeks
Secondary	Non-Alchoholic Fatty Liver Disease Fibrosis Score levels compare with baseline in 6 months	Non-Alchoholic Fatty Liver Disease Fibrosis Scoring, < -1.455 indicates Fibrosis Stage 0-2,; -1.455 to 0.676 is considered indeterminate fibrosis stage, > 0.676 indicates Fibrosis Stage 3-4	up to 24 weeks
Secondary	Frequency of adverse events in 6 months	Safety	up to 24 weeks