Study to Evaluate the Possible Antifibrotic Effect of Zinc Sulphate in Chronic HCV Patient Receiving Direct Acting Anti-viral Therapy.

October 14, 2023 updated by: Dina Samir Ahmed Attalla, Tanta University

Study to Evaluate the Possible Antifibrotic Effect of Zinc Sulphate in Chronic HCV Patient Receiving Direct Acting Anti-viral Therapy

This study aims to evaluate the possible antifibrotic effect of zinc sulphate in chronic HCV patient receiving direct acting anti-viral therapy

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury.

Removal or elimination of the causative agent such as control or cure of viral infection has shown that liver fibrosis is reversible. Thus, there is a huge unmet medical need for anti-fibrotic therapies to prevent liver disease progression and Hepatocellular Carcinoma (HCC) development. However, while many anti-fibrotic candidate agents have shown robust effects in experimental animal models, but uptill now, no approved therapy exists for liver fibrosis.

The once-daily oral combination of Daclatasvir 60 mg and Sofosbuvir 400 mg once daily, for the treatment of non-cirrhotic naïve patients with chronic hepatitis C virus genotype 4 infection for 12 weeks, is effective and well tolerated in these patients.

Zinc, an essential trace element, is involved in the enzymatic activities and structural maintenance of numerous enzymes and proteins, and it has various physiological roles in the body. Specifically, zinc works as a growth factor and exerts immunomodulatory , antioxidant, anti-apoptotic and anti-inflammatory effects.

Zinc deficiency is prevalent in cirrhosis patients, whereas nitrogen metabolic disorders, particularly hypoalbuminemia, can be an indicator of zinc deficiency.

Zinc supplementation therapy has a great benefit in the management of chronic liver disease and seems to improve liver pathology and reduce the incidence of liver fibrosis and HCC.

It has been found that zinc supplementation inhibited liver inflammation and fibrosis in bile duct ligation (BDL) mice through selective suppression of M1 macrophages.

Therefore, oral zinc supplementation is recommended as a means of suppressing HCC development in patients who have achieved sustained virological response (SVR) after direct acting antiviral therapies (DAAs) treatment . Zinc is a powerful supplement not only to increase SVR in non-responders but also to improve hepatic functions and fibrosis.

Fibronectin (FN), which is produced by hepatic stellate cells (HSCs), is a multifunctional glycoprotein and extracellular matrix (ECM) component that is present in the cell membrane and cytoplasm and associated with cell cycle progression, participates in cell adhesion and proliferation, and has an important role in fibrotic progression, excessive FN deposition occurs prior to collagen deposition.

Fibronectin expression was gradually increased in response to TGFβstimulation of HSCs, It is a good noninvasive marker for the assessment of liver fibrosis in patients with chronic HCV.

Transforming growth factor (TGF)-β is a master profibrogenic cytokine and a promising target to treat fibrosis.

Hyaluronic acid is a chief component of the extracellular matrix (ECM) of connective tissues and plays the main structural role in the formation of ECM. The most important organ involved in the synthesis of hyaluronic acid is the liver and the results of clinical studies have shown its high diagnostic sensitivity in the pathological processes of the liver.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Shibīn Al Kawm, Egypt
        • National Liver Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • • Patients with fibrosis stage (F1&F2) post chronic HCV infection.

    • Age > 18 and < 65 years.

Exclusion Criteria:

  • Patients with prior history of liver transplantation.
  • Patients with prior history of hepatocellular carcinoma.
  • Patients coinfected with HIV or HBV.
  • Patients with any malignancies.
  • Pregnant and lactating women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group 2
25 patients will receive 50mg Zinc Sulphate plus the standard direct acting anti-viral therapy for 3 months.
Drug: Zinc Supplement
Zinc sulphate 50 mg
No Intervention: Group 1
25 patients will receive their standard direct acting anti-viral therapy for 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Abdominal Ultrasonography
Time Frame: 3 months
Assessment the change in the degree of liver fibrosis post treatment and compare their results before and post treatment
3 months
Serum fibronectin level
Time Frame: 3 months
Fibronectin (FN), which is produced by hepatic stellate cells (HSCs), participates in cell adhesion and proliferation, and has an important role in fibrotic progression, excessive FN deposition occurs prior to collagen deposition
3 months
Serum transforming growth factor - beta 1 (TGF- β1) level
Time Frame: 3 months
Transforming growth factor (TGF)-β is a good noninvasive marker for the assessment of liver fibrosis in patients with chronic HCV and also considered as a master profibrogenic cytokine and a promising target to treat fibrosis (15)
3 months
Fibrosis-4 (FIB-4) Score
Time Frame: 3 months

The Fibrosis 4 score is a non-invasive scoring system based on several laboratory tests (AST/ALT/Platelets) that help to non-invasively estimate the amount of scarring in the liver. This score has been studied in liver disease due to Hepatitis C and Non-alcoholic steatohepatitis (NASH)

FIB-4 = (Age (years)XAST Level (U/L))/(Platelet Count (〖10〗^9/L) X √(ALT (U/L)))

FIB-4>3.25 confirms the presence of advanced fibrosis (F4)

FIB-4<1.45 exclude the presence of advanced fibrosis (F3-F4)

Values between 1.45 and 3.25 did not fully discriminate fibrosis and would need an additional method to predict liver fibrosis
3 months
AST to Platelet Ratio Index (APRI) score
Time Frame: 3 months

The APRI model was developed as a simple, easily calculated method to predict significant, severe fibrosis (or cirrhosis) and has been tested in persons with HCV mono-infection and those with HCV and HIV Co-infection

APRI = (AST Level /AST (Upper Limit of Normal))/(Platelet Count (〖10〗^9/L) )X100

If the score is less than or equal to 0.5, the liver is either completely free of fibrosis (F0), or has a tiny bit of scarring (F1 or F2 by METAVIR Score).

If the score is 1.5 or greater, the liver has scarring and likely some cirrhosis (F3 or F4 by METAVIR Score)
3 months
Serum hyaluronic acid level
Time Frame: 3 months
Hyaluronic acid is a chief component of the extracellular matrix (ECM) of connective tissues and The most important organ involved in the synthesis of hyaluronic acid is the liver
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tanta University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2022

Primary Completion (Actual)

January 1, 2023

Study Completion (Actual)

August 30, 2023

Study Registration Dates

First Submitted

July 13, 2022

First Submitted That Met QC Criteria

July 16, 2022

First Posted (Actual)

July 19, 2022

Study Record Updates

Last Update Posted (Actual)

October 17, 2023

Last Update Submitted That Met QC Criteria

October 14, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Clinical hepatology

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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