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Trial registered on ANZCTR


Registration number
ACTRN12624000039583
Ethics application status
Approved
Date submitted
9/08/2023
Date registered
17/01/2024
Date last updated
17/01/2024
Date data sharing statement initially provided
17/01/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating the effect of Dapagliflozin on Alanine Transaminase Levels in Type 2 Diabetic Patients with Non Alcoholic Fatty Liver Disease
Scientific title
Evaluating the effect of Dapagliflozin on Alanine Transaminase Levels in Type 2 Diabetic Patients with Non Alcoholic Fatty Liver Disease
Secondary ID [1] 310350 0
None
Universal Trial Number (UTN)
U1111-1296-4355
Trial acronym
DAPA-ALT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Alcoholic Steatohepatitis 331083 0
Type 2 Diabetes Mellitus 331549 0
Condition category
Condition code
Metabolic and Endocrine 327872 327872 0 0
Diabetes
Oral and Gastrointestinal 327873 327873 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients fulfilling the inclusion criteria of this study and randomized to treatment group would be offered Dapagliflozin/ Metformin 5 mg/1000 mg (5 mg of Dapagliflozin and 1000 mg of Metformin) tablets per oral twice daily treatment for 12 weeks . The treatment will be given as home self administered. Adherence would be monitored by drug tablet return.
Intervention code [1] 326750 0
Treatment: Drugs
Comparator / control treatment
Patients fulfilling the inclusion criteria of this study and randomized to comparator group would be offered Sitagliptin/ Metformin 50 mg/1000 mg (50 mg of Sitagliptin and 1000 mg of Metformin) tablets per oral twice daily treatment for 12 weeks . The treatment will be given as home self administered. Adherence would be monitored by drug tablet return.
Control group
Active

Outcomes
Primary outcome [1] 335719 0
Change in Alanine Transaminase(ALT) level using ALT blood test.
Timepoint [1] 335719 0
Baseline and 12 weeks post commencement of intervention.
Secondary outcome [1] 425302 0
Glycated Hemoglobin HbA1C levels using Hemoglobin A1C (HbA1C) blood test.
Timepoint [1] 425302 0
Baseline and 12 weeks post commencement of intervention.
Secondary outcome [2] 425303 0
Change in Weight in kilograms checked in clinic on a digital scale.
Timepoint [2] 425303 0
Baseline and 12 weeks post commencement of intervention.
Secondary outcome [3] 425304 0
Urinary tract infections by urine dipstick test.
Timepoint [3] 425304 0
Baseline and 12 weeks post commencement of intervention.
Secondary outcome [4] 425305 0
Genital Mycotic infections by history suggesting these infections and clinical examination.
Timepoint [4] 425305 0
Baseline by history, between baseline and and 12 weeks post commencement of intervention by history and clinical examination if symptomatic, and 12 weeks post commencement of intervention by history alone.

Eligibility
Key inclusion criteria
1. Age 16 years or older.
2. Gender: Any
3. Patients already diagnosed as having type 2 diabetes mellitus (Fasting blood glucose of >126 mg/dl or HbA1C > 6.5 %) , having suboptimal glycemic control (HbA1C > 7%) on current treatment who are having Alanine Transaminase (ALT)levels > 40IU/L and ultrasonographical features of Non Alcoholic Fatty Liver Disease (NAFLD).
Minimum age
16 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with type 1 diabetes mellitus (Sodium-Glucose Co Transporter 2 (SGLT2) inhibitors (SGLT2 inhibitors may precipitate Diabetic Ketoacidosis)

2. Pregnancy (SGLT2 inhibitors not licensed).

3. Patients already on SGLT2 inhibitors

4. Patients having impaired renal function (estimated Glomerular Filtration rate of < 45ml/min/1.73m2),

5. Patients having chronic liver disease, positive viral serology for hepatitis B and C, history of alcohol consumption, having clinical features of hyperthyroidism, recent infections, history of cancer and evidence of gall-stones/cholecystitis on ultrasound,

6. Patients having recent (within 6 months) acute coronary syndrome

7. Cancer of any sort.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomization
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size would be 192. The sample size is calculated with the help of OpenEpi sample size calculator, With confidence level (1-a) equal to 95%., power of test of 80% and previously reported normalization of ALT levels in 80% patients taking Dapagliflozin and Metformin vs 61.5 % in Sitagliptin or Linagliptin and metformin ( Choi DH, Jung CH, Mok JO, Kim CH, Kang SK, Kim BY. Effect of Dapagliflozin on Alanine Aminotransferase Improvement in Type 2 Diabetes Mellitus with Non-alcoholic Fatty Liver Disease. Endocrinol Metab (Seoul). 2018 Sep;33(3):387-394. doi: 10.3803/EnM.2018.33.3.387. PMID: 30229578; PMCID: PMC6145967.) The data will be analyzed by using standard SPSS software version 23. Comparisons between two groups will be evaluated by independent-samples t test for continuous variables such as ALT levels, HbA1C, Weight and chi-square test for categorical variables such as gender. Changes in clinical and laboratory parameters within each group will be tested by paired t test. Side effects, such as the presence of urinary tract infections and genital infections would be evaluated with the use of McNemar test.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2024
Actual
Date of last participant enrolment
Anticipated
31/01/2025
Actual
Date of last data collection
Anticipated
30/04/2025
Actual
Sample size
Target
192
Accrual to date
Final
Recruitment outside Australia
Country [1] 25702 0
Pakistan
State/province [1] 25702 0
Khyber Pakhtunkhwa

Funding & Sponsors
Funding source category [1] 314556 0
Hospital
Name [1] 314556 0
MTI Lady Reading Hospital
Country [1] 314556 0
Pakistan
Primary sponsor type
Hospital
Name
MTI Lady Reading Hospital
Address
MTI Lady Reading Hospital, Peshawar, Post code 25000.
Country
Pakistan
Secondary sponsor category [1] 316514 0
None
Name [1] 316514 0
Address [1] 316514 0
Country [1] 316514 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313593 0
Institutional Review Board MTI Lady Reading Hospital
Ethics committee address [1] 313593 0
MTI Lady Reading Hospital, Peshawar, Post code 25000.
Ethics committee country [1] 313593 0
Pakistan
Date submitted for ethics approval [1] 313593 0
06/09/2022
Approval date [1] 313593 0
22/09/2022
Ethics approval number [1] 313593 0
496/LRH/MTI

Summary
Brief summary
Both Sitagliptin and Dapagliflozin are widely used as adjuncts to Metformin in Type 2 Diabetes Mellitus (T2DM) patients in those having suboptimal glycemic control. It is estimated that Non-alcoholic fatty liver disease (NAFLD) affects approximately more than half of those with T2DM. Hepatic steatosis caused by NAFLD leads to increased levels of hepatic aminotransferases such that alanine aminotransferase (ALT) levels are more than those of aspartate aminotransferase (AST). To our knowledge no study on Dapagliflozin vs Sitagliptin in addition to Metformin has been carried out in Pakistan to see their effect on patients with T2DM and Non Alcoholic Steatohepatitis in terms of improvement of liver enzymes. The objective of this study is therefore to study the effect of Dapagliflozin 10 mg vs Sitagliptin 100 mg in addition to Metformin 2000 mg on ALT levels of T2DM patients who had more than Upper Limit Normal ALT and suboptimal glycemic control and having ultrasonographical evidence of NAFLD.
ALT levels of patients who meet the inclusion criteria would be collected at baseline and repeated at 12 weeks interval after treatment with either 10 mg /day of Dapagliflozin or 100 mg/day of Sitagliptin in addition to 2000 mg of Metformin/day. Similarly baseline and 12 weeks post treatment weight, HbA1C levels, Urinary Tract Infections and Genital Mycotic infection of these two groups would be recorded. Any particular difference between these parameters among these two groups would be found after completion of the trial using the statistical methods explained previously.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128678 0
Dr Nauman Wazir
Address 128678 0
Department of Diabetes and Endocrinology, MTI Lady Reading hospital, Peshawar, Post code 25000.
Country 128678 0
Pakistan
Phone 128678 0
+923369190857
Fax 128678 0
Email 128678 0
nauman.wazir@lrh.edu.pk
Contact person for public queries
Name 128679 0
Dr Nauman Wazir
Address 128679 0
Department of Diabetes and Endocrinology, MTI Lady Reading hospital, Peshawar, Post code 25000.
Country 128679 0
Pakistan
Phone 128679 0
+923369190857
Fax 128679 0
Email 128679 0
nauman.wazir@lrh.edu.pk
Contact person for scientific queries
Name 128680 0
Dr Nauman Wazir
Address 128680 0
Department of Diabetes and Endocrinology, MTI Lady Reading hospital, Peshawar, Post code 25000.
Country 128680 0
Pakistan
Phone 128680 0
+923369190857
Fax 128680 0
Email 128680 0
nauman.wazir@lrh.edu.pk

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data underlying published results only
When will data be available (start and end dates)?
Immediately following publication, no end date.
Available to whom?
Case-by-case basis at the discretion of Primary Sponsor, etc.
Available for what types of analyses?
IPD meta-analyses
How or where can data be obtained?
Access subject to approvals by Principal Investigator
Dr. Nauman Wazir
nauman.wazir@lrh.edu.pk


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
19971Informed consent form    386405-(Uploaded-09-08-2023-20-42-40)-Study-related document.pdf
19972Ethical approval    386405-(Uploaded-09-08-2023-20-43-50)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.