Efficacy of Empagliflozin and Pioglitazone in Diabetic Patients With NAFLD

• ClinicalTrials.gov Identifier: NCT05942963
• Recruitment Status: Not yet recruiting
• First Posted: July 12, 2023
• Last Update Posted: July 12, 2023
• Sponsor: Jinnah Postgraduate Medical Centre
• Information provided by (Responsible Party): ZA, Jinnah Postgraduate Medical Centre

Study Description

Brief Summary:

This clinical trial will yield results about the therapeutic effect of combining pioglitazone with SGLT2i in people suffering from NAFLD associated with T2DM. Study participants will be asked to fill out a few questions on proforma that will obtain demographic information as well as information relating to their health. In addition, some blood tests will be done following standard procedures.

Condition or disease	Intervention/treatment	Phase
Non-Alcoholic Fatty Liver Disease; Type2diabetes	Drug: Empagliflozin 10 MG; Drug: Pioglitazone 15mg; Drug: Metformin	Phase 4

Detailed Description:

This is a randomized clinical trial conducted to compare the efficacies of pioglitazone and empagliflozin in people suffering from NAFLD associated with T2DM.

Randomization will be done using card randomization. Four different color-coded cards will be kept. Any card will be randomly picked for the patient fulfilling inclusion criteria and will be treated according to the allocated treatment arm mentioned on the card

Written informed consent will be obtained from the immediate attendant of the patient. All ethical considerations will be followed.

Our research has been approved by Jinnah Sindh Medical University, Karachi. For this approval, the investigators have made every effort to ensure the confidentiality of research data collected from all our participants in this survey. The information collected will be stored with the investigators only in the form of de-identified information and will be retained in a secure place under lock and key. Any results that will be generated will be presented on a collective basis, and will not contain the participants name or any other personal details.

Data entry and analysis will be done using SPSS Software version 23. Study analysis will be done using the principle of intention to treat. The mean scores will be compared pre and post-intervention using paired t-test. The association of age, gender, and grade of fatty liver will be compared with different groups using correlation and regression models. All analyses will be at a confidence Interval of 95% and a p-value <.05.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: PEARL-DM: Efficacy of Empagliflozin and Pioglitazone in Diabetic Patients With NAFLD; Randomized Controlled Trial From Pakistan.
• Estimated Study Start Date: October 2023
• Estimated Primary Completion Date: April 2024
• Estimated Study Completion Date: April 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group A; SOC+ Empagliflozin + Pioglitazone	Drug: Empagliflozin 10 MG; 10-25 mg/day; Drug: Pioglitazone 15mg; 15-45 mg/day; Drug: Metformin; 1000mg-2850mg/ day
Experimental: Group B; SOC +Empagliflozin	Drug: Empagliflozin 10 MG; 10-25 mg/day; Drug: Metformin; 1000mg-2850mg/ day
Experimental: Group C; SOC+ Pioglitazone	Drug: Pioglitazone 15mg; 15-45 mg/day; Drug: Metformin; 1000mg-2850mg/ day
Active Comparator: Group D; SOC only	Drug: Metformin; 1000mg-2850mg/ day

Outcome Measures

Primary Outcome Measures :

1. A change in liver steatosis will be assessed through fibro CAP score. [ Time Frame: Will be assessed at enrollment. ]
   Fibro-controlled attenuation parameter (fibro CAP). The parameter range is commonly between 100 and 400 dB/m, and the greater the reading worse will be the outcome.
2. A change in liver steatosis will be assessed through fibro CAP score. [ Time Frame: Will be assessed at 168th day post enrollment. ]
   Fibro-controlled attenuation parameter (fibro CAP). The parameter range is commonly between 100 and 400 dB/m, and the greater the reading worse will be the outcome.

Secondary Outcome Measures :

1. change in SF-36 scores [ Time Frame: Quality of life will be assessed 84th day post enrollment. ]
   36-Item Short Form Survey (SF-36) assesses eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. A higher score defines a more favorable health state.
2. change in SF-36 scores [ Time Frame: Quality of life will be assessed at day 252 post enrollment. ]
   36-Item Short Form Survey (SF-36) assesses eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. A higher score defines a more favorable health state.
3. change in liver fibrosis will be assessed through the FIB-4 index. [ Time Frame: at enrollment. ]
   Fibrosis-4 index (FIB-4). Low scores will indicate better outcomes (less fibrosis).
4. change in liver fibrosis will be assessed through the FIB-4 index. [ Time Frame: 84th day post enrollment. ]
   Fibrosis-4 index (FIB-4). Low scores will indicate better outcomes (less fibrosis).
5. change in liver fibrosis will be assessed through the FIB-4 index. [ Time Frame: at 168th day post enrollment. ]
   Fibrosis-4 index (FIB-4). Low scores will indicate better outcomes (less fibrosis).
6. change in liver fibrosis will be assessed through the FIB-4 index. [ Time Frame: at day 252 post enrollment. ]
   Fibrosis-4 index (FIB-4). Low scores will indicate better outcomes (less fibrosis).
7. change in liver fibrosis will be assessed through the APRI Score [ Time Frame: at enrollment. ]
   AST to platelet ratio index (APRI) Score. Lower the value better the outcome (less fibrosis)
8. change in liver fibrosis will be assessed through the APRI Score [ Time Frame: 84th day post enrollment. ]
   AST to platelet ratio index (APRI) Score. Lower the value better the outcome (less fibrosis)
9. change in liver fibrosis will be assessed through the APRI Score [ Time Frame: at 168th day post enrollment. ]
   AST to platelet ratio index (APRI) Score. Lower the value better the outcome (less fibrosis)
10. change in liver fibrosis will be assessed through the APRI Score. [ Time Frame: at day 252 post enrollment. ]
    AST to platelet ratio index (APRI) Score. Lower the value better the outcome (less fibrosis)
11. change in liver fibrosis will be assessed through the NFS Score. [ Time Frame: at enrollment. ]
    NAFLD fibrosis score (NFS). Lower the value better the outcome (less fibrosis)
12. change in liver fibrosis will be assessed through the NFS Score. [ Time Frame: at 84th day post enrollment. ]
    NAFLD fibrosis score (NFS). Lower the value better the outcome (less fibrosis)
13. change in liver fibrosis will be assessed through the NFS Score. [ Time Frame: at 168th day post enrollment. ]
    NAFLD fibrosis score (NFS). Lower the value better the outcome (less fibrosis)
14. change in liver fibrosis will be assessed through the NFS Score. [ Time Frame: at day 252 post enrollment. ]
    NAFLD fibrosis score (NFS). Lower the value better the outcome (less fibrosis)
15. Change in hepatic steatosis through the FLI score. [ Time Frame: at enrollment. ]
    Fatty liver index (FLI). Lower the value better the outcome
16. Change in hepatic steatosis through the FLI score. [ Time Frame: at 84th day post enrollment. ]
    Fatty liver index (FLI). Lower the value better the outcome
17. Change in hepatic steatosis through the FLI score. [ Time Frame: at 168th day post enrollment. ]
    Fatty liver index (FLI). Lower the value better the outcome
18. Change in hepatic steatosis through the FLI score. [ Time Frame: at day 252 post enrollment. ]
    Fatty liver index (FLI). Lower the value better the outcome
19. Change in Insulin resistance will be assessed through HOMA-2IR/IR scale. [ Time Frame: at enrollment. ]
    homeostatic model assessment-2IR (HOMA-2IR/IR). The lower the value better the outcome.
20. Change in Insulin resistance will be assessed through HOMA-2IR/IR scale. [ Time Frame: at 84th day post enrollment. ]
    homeostatic model assessment-2IR (HOMA-2IR/IR). The lower the value better the outcome.
21. Change in Insulin resistance will be assessed through HOMA-2IR/IR scale. [ Time Frame: at 168th day post enrollment. ]
    homeostatic model assessment-2IR (HOMA-2IR/IR). The lower the value better the outcome
22. Change in Insulin resistance will be assessed through HOMA-2IR/IR scale. [ Time Frame: at day 252 post enrollment. ]
    homeostatic model assessment-2IR (HOMA-2IR/IR). The lower the value better the outcome.
23. Change in the LFT. [ Time Frame: At enrollment. ]
    Liver Function test (LFT) such as alanine transaminase, aspartate transaminase, bilirubin, albumin, alkaline phosphatase, gamma-glutamyl transferase .
24. Change in the LFT. [ Time Frame: 84th day post enrollment. ]
    Liver Function test (LFT) such as alanine transaminase, aspartate transaminase, bilirubin, albumin, alkaline phosphatase, gamma-glutamyl transferase .
25. Change in the LFT. [ Time Frame: at 168th day post enrollment. ]
    Liver Function test (LFT) such as alanine transaminase, aspartate transaminase, bilirubin, albumin, alkaline phosphatase, gamma-glutamyl transferase .
26. Change in the LFT. [ Time Frame: at day 252 post enrollment. ]
    Liver Function test (LFT) such as alanine transaminase, aspartate transaminase, bilirubin, albumin, alkaline phosphatase, gamma-glutamyl transferase .
27. Change in weight [ Time Frame: at enrollment. ]
    weight. lower the levels better the outcome.
28. Change in weight [ Time Frame: at 84th day post enrollment. ]
    weight. lower the levels better the outcome.
29. Change in weight [ Time Frame: at 168th day post enrollment. ]
    weight. lower the levels better the outcome.
30. Change in weight [ Time Frame: at day 252 post enrollment. ]
    weight. lower the levels better the outcome.
31. Change in random blood sugar [ Time Frame: at enrollment. ]
    random blood sugar
32. Change in random blood sugar [ Time Frame: at 84th day post enrollment. ]
    random blood sugar.
33. Change in random blood sugar [ Time Frame: at 168th day post enrollment. ]
    random blood sugar.
34. Change in random blood sugar [ Time Frame: at day 252 post enrollment. ]
    random blood sugar. lower the levels better the outcome.
35. Change in waist circumference [ Time Frame: at enrollment. ]
    waist circumference. lower the levels better the outcome.
36. Change in waist circumference [ Time Frame: at 84th day post enrollment. ]
    waist circumference. lower the levels better the outcome.
37. Change in waist circumference [ Time Frame: at 168th day post enrollment. ]
    waist circumference. lower the levels better the outcome.
38. Change in waist circumference [ Time Frame: at day 252 post enrollment. ]
    waist circumference. lower the levels better the outcome.
39. Change in HbA1c [ Time Frame: at enrollment. ]
    hemoglobin A1c (HbA1c).lower the levels better the outcome.
40. Change in HbA1c [ Time Frame: at 84th day post enrollment. ]
    hemoglobin A1c (HbA1c).lower the levels better the outcome.
41. Change in HbA1c [ Time Frame: at 168th day post enrollment. ]
    hemoglobin A1c (HbA1c).lower the levels better the outcome.
42. Change in HbA1c [ Time Frame: at day 252 post enrollment. ]
    hemoglobin A1c (HbA1c).lower the levels better the outcome.
43. Change in Body mass index [ Time Frame: at enrollment. ]
    Body mass index. lower the levels better the outcome.
44. Change in body mass index [ Time Frame: at 84th day post enrollment. ]
    body mass index. lower the levels better the outcome.
45. Change in body mass index [ Time Frame: at 168th day post enrollment. ]
    body mass index. lower the levels better the outcome.
46. Change in body mass index [ Time Frame: at day 252 post enrollment. ]
    body mass index. lower the levels better the outcome.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• T2DM patients with NAFLD glycated
• APRI scores of more than 1.5

Exclusion Criteria:

• Patients having type 1 diabetes
• evidence of advanced/decompensated cirrhosis (on the basis of a Child-Pugh score of more than 7 and MELD of more than 15)
• hepatocellular carcinoma (evidence on ultrasound or alpha-fetoprotein)
• patient suffering from acute or chronic hepatitis
• biliary disease
• HIV
• hemochromatosis
• autoimmune conditions (alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson's disease)
• renal dysfunction with GFR [eGFR] <30 mL/min/1.73m2
• history of alcohol ( male >30 g/d and female;20 g/d)
• history of cancer or undergoing treatment for cancer,
• use of amiodarone, tamoxifen, sodium valproate, corticosteroids, methotrexate, ursodeoxycholic acid, S-adenosyl methionine, betaine, silymarin, gemfibrozil
• using supplements including vitamin E, vitamin C, zinc, and selenium or antioxidant agents over the last 3 months
• history of cardiovascular events within the past 3 months
• pregnancy or breastfeeding
• contraindications to empagliflozin use (history of recurrent urogenital infections, current or previous gangrene, or hypersensitivity reaction to the molecule)
• history of bladder cancer
• morbid obesity (BMI greater than 35).

Contacts and Locations

Locations

Pakistan

Medical ICU, Jinnah Postgraduate Medical Centre

Karachi, Sindh, Pakistan, 71550

Sponsors and Collaborators

Jinnah Postgraduate Medical Centre

More Information

• Responsible Party: ZA, Associate professor, Jinnah Postgraduate Medical Centre
• ClinicalTrials.gov Identifier: NCT05942963
• Other Study ID Numbers: JSMU/IRB/2023/709
• First Posted: July 12, 2023
• Last Update Posted: July 12, 2023
• Last Verified: July 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases; Metformin; Pioglitazone; Empagliflozin; Hypoglycemic Agents; Physiological Effects of Drugs; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action