Non-Alcoholic Steatohepatitis (NASH)
Conditions
Keywords
NASH, Roflumilast, LSM, TNF-α, MDA, TGF-ß1
Brief summary
Study type :clinical trial Main purpose :esnsure safety and efficacy of Roflumilast to treat patients with Non-Alcoholic Steatohepatitis Background and aim: Non-alcoholic fatty liver disease is the most prevalent chronic liver disease globally. There is no defined therapy for non-alcholic steatohepatitis (NASH), therefore this study aimed at evaluating the efficacy and safety of Roflumilast in patients with non-alcoholic NASH. Methods: This randomized controlled parallel study involved 55 patients with NASH who were randomized into vitamin E group or control group (n=24) which received vitamin E 1000 mg once daily and roflumilast group (n=31) which received roflumilast 500 μg once daily for three months. Patients were assessed at baseline and after intervention through liver stiffness measurement (LSM) using fibro-scan and through evaluation of serum levels of tumor necrosis factor -alpha (TNF-α), Malondialdehyde (MDA), transforming growth factor-beta 1 (TGF-ß1). In addition, liver enzymes, lipid panel, fasting blood glucose and fasting insulin level with subsequent calculation of the homeostatic model assessment for Insulin resistance (HOMA-IR) were also assessed.
Interventions
Patients in this group received roflumilast 500 μg once daily for three months.
vitamin E group or control group (n=24) which received vitamin E 1000 mg once daily
Sponsors
Tanta University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
This study was a randomized controlled parallel study. Patients were recruited from out-patient clinic of Tropical medicine department, Tanta university hospital, Tanta, Egypt. The study involved 55 patients with NASH who were randomized using sealed envelope methods with assignment codes for each available allocation into vitamin E group or control group (n=24) which received vitamin E 1000 mg once daily and roflumilast group (n=31) which received roflumilast 500 μg once daily. The study duration was 3 months whereas patients were assessed at baseline and 3 months after intervention. The study was conducted following the ethical standards of Helsinki declaration in 1964 and its later amendments. The study was approved by Research Ethical committee of Tanta University (approval code:35336/3/22).participants gave their written informed consent.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with Cytokeratine level \>240 IU/L. * Adult patient (age \> 18 years old). * Both sex. * Overweight and obese. * Patients with evidence of steatosis through imaging. * Patient with mild to moderate elevation in aminotransferase activity (\>2 ,but \<5 times upper limit of normal ). * Patient with Hepatic steatosis index (HSI) \> 36. * Patient with HAIR ( hypertension ,alanine aminotransferase level ,insulin resistance ) of 2 or 3. * Fibroscan score \>7Kpa and \< 12.5 Kpa (F2 - F3).
Exclusion criteria
* Alcohol consumer and smokers * Patients with Wilson's disease and hemochromatosis . * Patients with viral hepatitis. * Patients with cirrhosis . * Patients with inflammatory diseases . * Patients with other comorbid disease that elevate transaminases (congestive heart failure and malignancy). * Patients on medications that interfere with lipid and carbohydrate metabolism.. * Patients on stateogenic medications. * Pregnancy and lactating women. * Females on oral contraceptive pills.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in liver stiffness measurement (LSM) measured by fibroscan score | 12 weeks following the end of treatment | Liver Stiffness measurement (LSM) by fibro-scan. Transient elastography (Fibroscan, Echosens, Paris) was used to assess liver stiffness depending up-on the method formerly prescribed .Through a single independent operator, at least ten valid measurements were obtained for each patient. Results were included in the final analysis only if the following three criteria were met: at least ten valid measurements, success rate \>60% and the interquartile range (IQR)-to-liver stiffness ratio was ≤0.30. The median values of the validated measurements for each patient were representative to the liver stiffness and expressed in units of kilopascals (kPa) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The change in liver panel parameters | 3 months after treatment | Blood sample collection and biochemical measurement of Approximately 10 ml of venous blood was taken from each patient after overnight fasting by sterile venipuncture, without frothing and after minimal venous stasis using disposable syringes. Blood samples were delivered in a vacutainer serum separator tubes. Immediate centrifugation at 3000 rpm was performed and then the serum was separated and divided into two portions. The first portion was used for determination of fasting blood glucose (glucose oxidase method), liver enzymes aspartate transaminase AST, alanine transaminase ALT and gamma-glutamyl transaminase GGT (spectrophotometerially) and lipid panel (enzymatic colorimeteric method). |
| Improvement in HOMA IR | 12 weeks following the end of treatment | HOMA-IR is calculated as \[Fasting Insulin (μg/ml)\]\*\[Fasting Glucose (mmol/l)\]/22.5,HOMA-IR values between 0.5 and 1.4 are considered normal, ≥1.9 are indicative of early IR, and ≥2.9 indicate IR |
Countries
Egypt
Outcome results
None listed