Hepatitis CPhase 3NCT05465434
Study to Evaluate the Possible Antifibrotic Effect of Zinc Sulphate in Chronic HCV Patient Receiving Direct Acting Anti-viral Therapy.
A Phase 3 study testing Zinc Supplement in people with Hepatitis C, run by Tanta University at 1 site in Egypt.
Trial summary
This study aims to evaluate the possible antifibrotic effect of zinc sulphate in chronic HCV patient receiving direct acting anti-viral therapy Read more about this study
- Who is it for?
- Ages 19 to 65 years
- Conditions the study is for
- Hepatitis C
- What is being tested?
- Zinc Supplement
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Aug 2022to 30 Aug 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • Patients with fibrosis stage (F1\&F2) post chronic HCV infection.
- Age > 18 and < 65 years.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
Read the 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.
- Conditions
- Hepatitis C
- Being tested
- Zinc Supplement
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zinc SupplementDrug
Zinc sulphate 50 mg
| Study group | Role | What they receive |
|---|---|---|
| Group 2 | Active comparator | 25 patients will receive 50mg Zinc Sulphate plus the standard direct acting anti-viral therapy for 3 months. Receives: Drug: Zinc Supplement |
| Group 1 | No intervention | 25 patients will receive their standard direct acting anti-viral therapy for 3 months |
What is being measured
The primary outcome is the main question the study is designed to answer.
Abdominal Ultrasonography
Assessment the change in the degree of liver fibrosis post treatment and compare their results before and post treatment
Measured: 3 months
Serum fibronectin level
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
Measured: 3 months
Serum transforming growth factor - beta 1 (TGF- β1) level
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)
Measured: 3 months
Fibrosis-4 (FIB-4) Score
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
Measured: 3 months
AST to Platelet Ratio Index (APRI) score
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)
Measured: 3 months
Serum hyaluronic acid level
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
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2022
- Study start1 Aug 2022
- Primary completion1 Jan 2023
- Study completion30 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by Tanta UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tanta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dina Samir Ahmed Attalla, Tanta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05465434
- Sponsor's protocol ID
- Clinical hepatology
- Status last verified
- Oct 2023
- First submitted
- 13 Jul 2022
- Last updated
- 17 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
El-Haggar SM, Attalla DS, Elhelbawy M, El-Afify DR. A randomized clinical study to evaluate the possible antifibrotic effect of zinc sulfate in chronic HCV patient receiving direct-acting anti-viral therapy. Inflammopharmacology. 2025 Jan;33(1):329-339. doi: 10.1007/s10787-024-01628-3. Epub 2025 Jan 9.
PubMed 39789197
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Evaluate the Possible Antifibrotic Effect of Zinc Sulphate in Chronic HCV Patient Receiving Direct Acting Anti-viral Therapy
- ClinicalTrials.gov ID
- NCT05465434
- Acronym / sponsor ID
- Clinical hepatology
- Conditions
- Hepatitis C
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Tanta UniversityUniversity, hospital or other
- Study start
- 1 Aug 2022 (actual)
- Primary completion
- 1 Jan 2023 (actual)
- Study completion
- 30 Aug 2023 (actual)
- First posted
- 19 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to evaluate the possible antifibrotic effect of zinc sulphate in chronic HCV patient receiving direct acting anti-viral therapy
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 design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 2 | Active comparator | Drug: Zinc Supplement25 patients will receive 50mg Zinc Sulphate plus the standard direct acting anti-viral therapy for 3 months. |
| Group 1 | No intervention | –25 patients will receive their standard direct acting anti-viral therapy for 3 months |
Who may qualify
- Ages
- 19 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- • Patients with fibrosis stage (F1\&F2) post chronic HCV infection.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zinc SupplementZinc sulphate 50 mg | Drug | Group 2 |
Primary outcome
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
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
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)
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
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)
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2023.
- Derived from this study: PubMed 39789197El-Haggar SM, Attalla DS, Elhelbawy M, El-Afify DR. A randomized clinical study to evaluate the possible antifibrotic effect of zinc sulfate in chronic HCV patient receiving direct-acting anti-viral therapy. Inflammopharmacology. 2025 Jan;33(1):329-339. doi: 10.1007/s10787-024-01628-3. Epub 2025 Jan 9.
- Chronic hepatitis C and liver fibrosis , Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic valueLink provided by the sponsor.
- Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives , ummarize cellular drivers and molecular mechanisms of fibrogenesis in chronic liver diseases and discuss their impact for the development of urgently needed anti-fibrotic therapies.Link provided by the sponsor.
- Sustained virological response in patients with HCV treated with daclatasvir plus sofosbuvir, with or without ribavirinLink provided by the sponsor.
- Ledipasvir/Sofosbuvir versus Daclatasvir/Sofosbuvir for the Treatment of Chronic Hepatitis C Genotype 4 PatientsLink provided by the sponsor.
- Associations between Zinc Deficiency and Metabolic Abnormalities in Patients with Chronic Liver DiseaseLink provided by the sponsor.
- Zinc and protein metabolism in chronic liver diseasesLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Zinc Supplement in people with Hepatitis C, run by Tanta University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Abdominal Ultrasonography (time frame: 3 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05465434, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2023.