Evaluating the Efficacy and Safety of Roflumilast in Patients with NASH

NCT06677788 | Completed Phase 2 FDA Drug

• 1 other identifier: 35336/3/22
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Alcoholic Steatohepatitis (NASH)

Keywords

NASH; Roflumilast; LSM; TNF-α; MDA; TGF-ß1

Outcome Measures

Primary Outcomes (1)

• Change in liver stiffness measurement (LSM) measured by fibroscan score

  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)

  12 weeks following the end of treatment

Secondary Outcomes (2)

• The change in liver panel parameters

  3 months after treatment

• Improvement in HOMA IR

  12 weeks following the end of treatment

Study Arms (2)

Roflumilast group (n=31)

ACTIVE COMPARATOR

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.

Drug: Roflumilast 500 Mcg Oral Tablet

Vitamin E group or control group (n=24)

ACTIVE COMPARATOR

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.

Drug: Vitamin E capsule

Interventions

Roflumilast 500 Mcg Oral Tablet DRUG

Patients in this group received roflumilast 500 μg once daily for three months.

Roflumilast group (n=31)

Vitamin E capsule DRUG

vitamin E group or control group (n=24) which received vitamin E 1000 mg once daily

Vitamin E group or control group (n=24)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Tanta University

Tanta, Gharbia Governorate, 6620010, Egypt

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Roflumilast; Tablets; Vitamin E

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Tarek Mohamed Mostafa, Professor of clinical pharmacy

  Faculty of Pharmacy , Tanta University, Tanta, Egypt

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Model Details: 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.

Study Record Dates

• First Submitted: November 1, 2024
• First Posted: November 7, 2024
• Study Start: April 1, 2022
• Primary Completion: September 20, 2024
• Study Completion: October 15, 2024
• Last Updated: November 7, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact Mokhtaarsalem@gmail.com

Locations

EG (1)