Evaluating the Efficacy and Safety of Roflumilast in Patients with NASH

Tanta University

Status and phase: Completed; Phase 2

Conditions: Non-Alcoholic Steatohepatitis (NASH)

Treatments: Drug: Roflumilast 500 Mcg Oral Tablet; Drug: Vitamin E capsule

Study type: Interventional

Funder types: Other

Identifiers

NCT06677788

35336/3/22

Details and patient eligibility

About

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.

Enrollment: 55 patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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55 participants in 2 patient groups

Roflumilast group (n=31)

Active Comparator group

Description:

Arm Description: 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 homeostatic model assessment for Insulin resistance (HOMA-IR) were also assessed.

Treatment:

Drug: Roflumilast 500 Mcg Oral Tablet

Vitamin E group or control group (n=24)

Active Comparator group

Description:

vitamin E group or control group (n=24) which received vitamin E 1000 mg once daily. 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 homeostatic model assessment for Insulin resistance (HOMA-IR) were also assessed.

Treatment:

Drug: Vitamin E capsule