Clinical trial NCT05459701: Dapagliflozin in Type 2 Diabetes Mellitus Patients (T2DM) With Nonalcoholic Fatty Liver Disease (NAFLD)
Official title: The Hepato-protective Effect of Dapagliflozin in Type 2 Diabetes Mellitus Patients (T2DM) With Nonalcoholic Fatty Liver Disease (NAFLD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Nonalcoholic Fatty Liver Disease
Type 2 Diabetes
Lead sponsor: Damanhour University
Sponsor class: OTHER
Collaborators: name: University of Alexandria
First posted: 2022-07-15
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, randomized (1:1), double-blind clinical trial, will be carried out on 50 patients who are candidate to detect the hepato-protective effect of Dapagliflozin on diabetic type 2 patients with non- alcoholic fatty disease (dapagliflozin 10 mg once daily for 24 - 48 weeks

-Patients will be randomly allocated into two equal groups (25 patients each); group (A) for controlled (placebo), and the other group (D) for Dapagliflozin.
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the effect of dapagliflozin on liver function of patient with NAFLD and T2DM.

Detailed description: 1. Ethical committee approval will be obtained from Ethics committee of Faculty of Pharmacy, Damanhour University.
2. Ethical committee approval will be obtained from Ethics committee of General Organization for Teaching Hospitals and Institutes.
3. About 50 patients who are candidate to detect the hepato-protective effect of Dapagliflozin on non- alcoholic fatty disease, will be recruited from Alexandria Teaching Hospital (EL-Mery), General Organization for Teaching Hospitals and Institutes.
4. All participants should agree to take part in this clinical study and will provide informed consent.
5. Demographic data; age (year), sex (female/male), weight (kg), height (cm), BMI (kg/m2) will be collected.
6. Venous blood samples (5 ml will be collected by a sterile syringe then placed in a suitable sterile tube to be centrifuged, the serum will be reserved and stored at -80°C until the analysis) before, and after receiving medication (Dapagliflozin).
7. Measuring outcome:

   1. The biochemical tests will be done on the patients are alanine aminotransferase (ALT), aspartate aminotransferase (AST), homeostasis model assessment of insulin resistance (HOMA-IR), Hemoglobin A1C (HbA1C), Low-density lipoproteins (LDL), High-density lipoproteins (HDL), Triglycerides (TG), liver fibrosis score, and complete blood count (CBC).
   2. The molecular tests will be done on the patient are soluble vascular cell adhesion molecule-1 (Svcam-1), adipocytes (e.g. adiponectin, leptin).
8. The ultrasound screening will be done at first examination.
9. Statistical tests appropriate to the study design will be conducted to evaluate the significance of the results.
10. Results, conclusion, discussion and recommendations will be given.

Eligibility criteria: Inclusion Criteria:

1. Type 2 diabetes mellitus patients.
2. HbA1C \< 8.5.
3. Patients were They were having fatty liver changes on abdominal ultrasound and mild to moderate elevation of serum liver enzymes.
4. BMI more than 30

Exclusion Criteria:

1. Patients with a history of alcohol, smoking, uncontrolled diabetes.
2. (HbA1c \> 9.0).
3. Pregnancy.
4. Lactation.
5. Hemochromatosis.
6. Thyroid disorders.
7. Renal dysfunction.
8. Cardiac problem.
9. Chronic liver and decompensated liver disease in the form of hepatitis B and C.

Primary outcomes:
measure: leptin (ng/ml)
timeFrame: 6 months
measure: adiponectin (pg/ml)
timeFrame: 6 months
measure: VCAM-1 (ng/ml)
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Damanhūr
country: Egypt
facility: Rehab Hussein Werida
state: Elbehairah
Study officials:
affiliation: Damanhour University
name: Rehab H Werida, Ass Prof.
role: STUDY_CHAIR
affiliation: Damanhour University
name: Amira B. Kassem, Lecturer
role: PRINCIPAL_INVESTIGATOR
affiliation: Damanhour University
name: Yasmin Essam, Bachlor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chiba Y, Yamada T, Tsukita S, Takahashi K, Munakata Y, Shirai Y, Kodama S, Asai Y, Sugisawa T, Uno K, Sawada S, Imai J, Nakamura K, Katagiri H. Dapagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, Acutely Reduces Energy Expenditure in BAT via Neural Signals in Mice. PLoS One. 2016 Mar 10;11(3):e0150756. doi: 10.1371/journal.pone.0150756. eCollection 2016.
citation: Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, Takasu T, Imamura M, Li Q, Tomiyama H, Kobayashi Y, Noda A, Sasamata M, Shibasaki M. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol. 2013 Sep 5;715(1-3):246-55. doi: 10.1016/j.ejphar.2013.05.014. Epub 2013 May 23.
citation: Ohki T, Isogawa A, Toda N, Tagawa K. Effectiveness of Ipragliflozin, a Sodium-Glucose Co-transporter 2 Inhibitor, as a Second-line Treatment for Non-Alcoholic Fatty Liver Disease Patients with Type 2 Diabetes Mellitus Who Do Not Respond to Incretin-Based Therapies Including Glucagon-like Peptide-1 Analogs and Dipeptidyl Peptidase-4 Inhibitors. Clin Drug Investig. 2016 Apr;36(4):313-9. doi: 10.1007/s40261-016-0383-1.