Clinical trial NCT05942963: Efficacy of Empagliflozin and Pioglitazone in Diabetic Patients With NAFLD
Official title: PEARL-DM: Efficacy of Empagliflozin and Pioglitazone in Diabetic Patients With NAFLD; Randomized Controlled Trial From Pakistan.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Non-Alcoholic Fatty Liver Disease
Type2diabetes
Lead sponsor: Jinnah Postgraduate Medical Centre
Sponsor class: OTHER_GOV
First posted: 2023-07-12
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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 \&lt;.05.

Eligibility 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 \[eGFR\] \&lt;30 mL/min/1.73m2
* history of alcohol ( male \&gt;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).

Primary outcomes:
measure: A change in liver steatosis will be assessed through fibro CAP score.
timeFrame: Will be assessed at enrollment.
measure: A change in liver steatosis will be assessed through fibro CAP score.
timeFrame: Will be assessed at 168th day post enrollment.
Secondary outcomes:
measure: change in SF-36 scores
timeFrame: Quality of life will be assessed 84th day post enrollment.
measure: change in SF-36 scores
timeFrame: Quality of life will be assessed at day 252 post enrollment.
measure: change in liver fibrosis will be assessed through the FIB-4 index.
timeFrame: at enrollment.
measure: change in liver fibrosis will be assessed through the FIB-4 index.
timeFrame: 84th day post enrollment.
measure: change in liver fibrosis will be assessed through the FIB-4 index.
timeFrame: at 168th day post enrollment.
measure: change in liver fibrosis will be assessed through the FIB-4 index.
timeFrame: at day 252 post enrollment.
measure: change in liver fibrosis will be assessed through the APRI Score
timeFrame: at enrollment.
measure: change in liver fibrosis will be assessed through the APRI Score
timeFrame: 84th day post enrollment.
measure: change in liver fibrosis will be assessed through the APRI Score
timeFrame: at 168th day post enrollment.
measure: change in liver fibrosis will be assessed through the APRI Score.
timeFrame: at day 252 post enrollment.
measure: change in liver fibrosis will be assessed through the NFS Score.
timeFrame: at enrollment.
measure: change in liver fibrosis will be assessed through the NFS Score.
timeFrame: at 84th day post enrollment.
measure: change in liver fibrosis will be assessed through the NFS Score.
timeFrame: at 168th day post enrollment.
measure: change in liver fibrosis will be assessed through the NFS Score.
timeFrame: at day 252 post enrollment.
measure: Change in hepatic steatosis through the FLI score.
timeFrame: at enrollment.
measure: Change in hepatic steatosis through the FLI score.
timeFrame: at 84th day post enrollment.
measure: Change in hepatic steatosis through the FLI score.
timeFrame: at 168th day post enrollment.
measure: Change in hepatic steatosis through the FLI score.
timeFrame: at day 252 post enrollment.
measure: Change in Insulin resistance will be assessed through HOMA-2IR/IR scale.
timeFrame: at enrollment.
measure: Change in Insulin resistance will be assessed through HOMA-2IR/IR scale.
timeFrame: at 84th day post enrollment.
measure: Change in Insulin resistance will be assessed through HOMA-2IR/IR scale.
timeFrame: at 168th day post enrollment.
measure: Change in Insulin resistance will be assessed through HOMA-2IR/IR scale.
timeFrame: at day 252 post enrollment.
measure: Change in the LFT.
timeFrame: At enrollment.
measure: Change in the LFT.
timeFrame: 84th day post enrollment.
measure: Change in the LFT.
timeFrame: at 168th day post enrollment.
measure: Change in the LFT.
timeFrame: at day 252 post enrollment.
measure: Change in weight
timeFrame: at enrollment.
measure: Change in weight
timeFrame: at 84th day post enrollment.
measure: Change in weight
timeFrame: at 168th day post enrollment.
measure: Change in weight
timeFrame: at day 252 post enrollment.
measure: Change in random blood sugar
timeFrame: at enrollment.
measure: Change in random blood sugar
timeFrame: at 84th day post enrollment.
measure: Change in random blood sugar
timeFrame: at 168th day post enrollment.
measure: Change in random blood sugar
timeFrame: at day 252 post enrollment.
measure: Change in waist circumference
timeFrame: at enrollment.
measure: Change in waist circumference
timeFrame: at 84th day post enrollment.
measure: Change in waist circumference
timeFrame: at 168th day post enrollment.
measure: Change in waist circumference
timeFrame: at day 252 post enrollment.
measure: Change in HbA1c
timeFrame: at enrollment.
measure: Change in HbA1c
timeFrame: at 84th day post enrollment.
measure: Change in HbA1c
timeFrame: at 168th day post enrollment.
measure: Change in HbA1c
timeFrame: at day 252 post enrollment.
measure: Change in Body mass index
timeFrame: at enrollment.
measure: Change in body mass index
timeFrame: at 84th day post enrollment.
measure: Change in body mass index
timeFrame: at 168th day post enrollment.
measure: Change in body mass index
timeFrame: at day 252 post enrollment.
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Medical ICU, Jinnah Postgraduate Medical Centre
state: Sindh
Study officials:
References: