Efficacy and Safety of Dapagliflozin in Patients with Non-alcoholic Steatohepatitis

Sponsor
Cairo University
Study ID
NCT05254626
Phase
PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • Dapagliflozin 10Mg Tab — DRUG
    Dapagliflozin 10 mg, administered orally and to be prescribed for diabetic and non-diabetic patients with NASH for 24 weeks; in comparison to pioglitazone.
  • Pioglitazone 30 mg — DRUG
    Pioglitazone 30 mg, administered orally and to be prescribed for diabetic and non-diabetic patients with NASH for 24 weeks; as an active control and standard of care treatment.

Study Details

Patients with non-alcoholic fatty liver disease (NAFLD) are at increased risk of more aggressive liver disease; non-alcoholic steatohepatitis (NASH) and at a higher risk of death from cirrhosis, hepatocellular carcinoma and cardiovascular diseases. NAFLD is spreading as an epidemic in patients with metabolic syndrome. Its components include obesity, type 2 diabetes mellitus (T2DM) and dyslipidemia. The prevalence of NAFLD is likely to increase resulting in tremendous clinical, social and economic burdens. Unfortunately, there is no approved medication to treat patients with NASH-induced advanced fibrosis. Weight management is the first line of NASH treatment even in non-obese patients with at least 7% reduction of patient's weight. However, NASH patients need pharmacological treatment. Sodium glucose co-transporter (SGLT2) inhibitors demonstrated favorable effects on NAFLD without weight gain as an adverse event proposed by pioglitazone used for the same indication. SGLT2 inhibitors are able to reduce fatty liver content, as assessed by different imaging techniques, and improve biological markers of NAFLD, especially serum liver enzymes, in patients with or without T2DM. In addition, there are emerging data to suggest a mechanism beyond the reduction of body weight and hyperglycemia in patients with or without diabetes. This study aims to evaluate the efficacy and safety of SGLT2 inhibitors in NASH patients in comparison to pioglitazone. This is a randomized prospective parallel study, where all patients presented with NASH to the outpatient clinic in the National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; will be screened for specific inclusion and exclusion criteria. Diabetic and non-diabetic patients will be randomly assigned to receive one of two treatment modalities. The first arm will be the NASH patients receiving dapagliflozin and the second arm will be the NASH patients receiving pioglitazone for 24 weeks. Each group will have an equal number of diabetic and non-diabetic patients. All patients will be assessed for body composition, serum creatinine level, fasting blood glucose level, HbA1C, markers of insulin resistance (HOMA-IR), complete blood count, serum liver function tests, and NAFLD fibrosis score (NAS). Liver biopsy will be performed at baseline and at the end of the study and the total NAS score will be calculated. All patients will be assessed for any adverse drug reactions, and for their adherence by pill count method. Also, quality of life will be assessed for all patients using previously designed and validated questionnaire called Chronic Liver Disease Questionnaire (CLDQ).

Key Dates

Start date
Aug 1, 2022
Status verified
Sep 2024
Primary completion
Jan 23, 2024
Completion
Jul 23, 2024

Study Design

Enrollment
100 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Diabetic Group 1
    25 diabetic patients will be prescribed on dapagliflozin 10 mg - once daily (OD) - to be taken orally (PO) for 24 weeks
  • Active Comparator: Diabetic Group 2
    25 diabetic patients will be prescribed on Pioglitazone 30 mg - once daily (OD) - to be taken orally (PO) for 24 weeks
  • Experimental: Non-diabetic Group 1
    25 non-diabetic patients will be prescribed on dapagliflozin 10 mg - once daily (OD) - to be taken orally (PO) for 24 weeks.
  • Active Comparator: Non-diabetic Group 2
    25 non-diabetic patients will be prescribed on Pioglitazone 30 mg - once daily (OD) - to be taken orally (PO) for 24 weeks

Primary Outcome Measure

Histological Features (Liver Biopsy) [ Time Frame: Baseline and 24th week ]

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