Clinical trial NCT05644717: Effect of Erugliflozin On Liver Fat, Liver Fibrosis and Glycemic Control in Type II DM Patients With NASH/NAFLD
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Liver Fat
Liver Fibrosis
Glycemic Control
Body Weight Changes
Waist Circumference
Tolerance
Lead sponsor: Getz Pharma
Sponsor class: INDUSTRY
First posted: 2022-12-09
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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)


Eligibility criteria: 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

Primary outcomes:
measure: Radiologic liver parameters
timeFrame: up to 24 weeks
Secondary outcomes:
measure: HbA1c% levels compare with baseline in 6 months
timeFrame: up to 24 weeks
measure: Change in body weight compare with baseline in 6 months
timeFrame: up to 24 weeks
measure: Change in waist circumference compare with baseline in 6 months
timeFrame: up to 24 weeks
measure: Fibrosis 4 score levels compare with baseline in 6 months
timeFrame: up to 24 weeks
measure: Non-Alchoholic Fatty Liver Disease Fibrosis Score levels compare with baseline in 6 months
timeFrame: up to 24 weeks
measure: Frequency of adverse events in 6 months
timeFrame: up to 24 weeks
Other outcomes:
Locations:
city: Peshawar
country: Pakistan
facility: North west general hospital
state: KPK
Study officials:
affiliation: Shifa International Hospital
name: Umar Raja, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
citation: 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.