Clinical trial NCT05041673: Anti-diabetic Drugs and Fatty Liver Management
Official title: Efficacy of Vildagliptin, Liraglutide and Empagliflozin in the Management of Fatty Liver Disease Among Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Fatty Liver, Nonalcoholic
Diabetes Mellitus, Type 2
Lead sponsor: Alexandria University
Sponsor class: OTHER
Collaborators: name: Eva Pharma
First posted: 2021-09-13
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Type 2 DM is one of the major risk factors for development of non-alcoholic fatty liver disease. The pooled prevalence of fatty liver among diabetics is 54% (95% CI 45%-64%). Until now there is no well-established treatment for fatty liver disease.

Study setting: Randomized controlled trial

Study population:

Patients with type 2 DM plus Fatty Liver.

Arms and Interventions

1. Experimental arms: Group 1: metformin +/- insulin +/- sulfonylurea Group 2: Metformin plus vildagliptin+/- insulin +/- sulfonylurea Group 3: Metformin plus liraglutide+/- insulin+/- sulfonylurea Group 4: Metformin plus empagliflozin +/- insulin +/- sulfonylurea

Detailed description: Rational: Type 2 DM is one of the major risk factors for development of non-alcoholic fatty liver disease. The pooled prevalence of fatty liver among diabetics is 54% (95% CI 45%-64%). Until now there is no well-established treatment for fatty liver disease.

Study setting: Randomized controlled trial

Study population:

Patients with type 2 DM plus Fatty Liver.

NAFLD diagnostic criteria:

* Fatty Liver Index (FLI) 60 or more plus Ultrasound features of fatty liver.

  - Inclusion criteria
  1. Age above 18. 2- HbA1C less than 10.

     Sample size: Based on the result reported by Armstrong et al, the proportion of patients on standard care who showed resolution of steatosis versus intervention group on liraglutide was 9% vs 39%, using power of 80%, precision of 5%, the minimal required sample size was 24 for each group and we increased it to 30 to compensate for drop-out. So, 120 subjects will be divided into 4 equal groups.

     Study Design: Interventional (Randomized Clinical Trial) Allocation: Randomized Intervention Model: Parallel Assignment Masking: No masking. Study duration: 12 months of follow up

     Data collection methods and tools

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  1. Filling the pre-designed structured interview questionnaire from patients that includes:

     * Demographic traits: age, sex, marital status, education, occupation and residency.
     * Habits: smoking, physical exercise, dietary habits, drug use.
     * Social history, focusing on smoking status, occupation, presence of children at home and plans for future pregnancy (as appropriate).
     * Drug history
  2. Clinical data about:

     * Present/ past/ family history on thyroid diseases, and autoimmune disease.
     * Comorbidities: hypertension, coronary heart disease, chronic obstructive air way disease (COPD), obesity and others.
     * Medications used: dose, frequency and route of administration.
     * Hospitalization.
     * Body measures: weight, height, body mass index (BMI), waist circumference.
     * Vital signs: pulse, blood pressure, heart rate.
     * The compliance was ascertained through direct questioning at each clinic visits and by inspecting her pill bottles.
     * Patient satisfaction and quality of life will be measured at baseline and at the end of Intervention.
  3. Investigations

     * Lab: HCV Ab, HBsAg, HBcAb, ALT, AST, GGT, FBS, HBA1c, PPBS, Fasting insulin, CBC, Cholesterol, LDL, HDL, TGs, uric acid.
     * Calculation of the following score FLI, NAFLD-LFS, FIB-4, NFS.
     * Imaging: ultrasound/FIBROSCAN/ MRI.
     * Adverse effects of the drugs were systematically identified by careful health interview and clinical examinations. T-Bil, AST, ALT, and hematological values were measured for evaluation at every outpatient clinic visit.

     Follow-up

     All patients were followed up for twelve months:
* Dietary follow up.
* Liver enzymes (ALT, AST and GGT) at least every 3 months and more if clinically indicated
* Scores follow up: NFS and FIB-4 every 3 months.
* Fibroscan at end of 1-year follow up.
* MRI at end of 1-year follow up.

Eligibility criteria: Inclusion Criteria:

* Type 2 DM with fatty liver disease.
* HbA1C less than 10.

Exclusion Criteria:

1. Alcohol intake.
2. BMI 40 or more.
3. CKD with e GFR less than 60.
4. chronic liver diseases (chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, hemochromatosis, alfa-1 antitrypsin deficiency)
5. Atherosclerotic cardiovascular disease.
6. Celiac disease.
7. Clinically evident liver cirrhosis.
8. Patients who have ever had medullary thyroid carcinoma (MTC) or who have a family member who has ever had and patients who have multiple endocrine neoplasia syndrome type 2 (MEN 2)

Primary outcomes:
measure: Change in steatosis as measured using CAP score (fibroscan) and MRI
timeFrame: 12 months
Secondary outcomes:
measure: Change in liver enzymes
timeFrame: 12 months
measure: Changes in fibrosis grade
timeFrame: 12 months
Other outcomes:
Locations:
city: Alexandria
country: Egypt
facility: Alexandria University.
Study officials:
References: