Liver FibrosisPhase 1/2NCT05224128
Effect of Imatinib in Advance Liver Fibrosis Patients
A Phase 1/2 study testing Imatinib 200mg in people with Liver Fibrosis, run by Research Institute for Gastroenterology and Liver Diseases (RIGLD) at 1 site in Iran.
Trial summary
When a recurrent, long-term injury and inflammation of the liver causes an excessive accumulation of damaged tissue, a dangerous condition called liver fibrosis develops. Most chronic liver diseases eventually lead to fibrosis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Fibrosis
- What is being tested?
- Imatinib 200mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteIran
- Study dates
- 20 Feb 2021to 2 Sep 2022
- Phase
- Phase 1/2
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females between18-75 years old with a clinically confirmed diagnosis of Fibrosis with grade 3-4 by Metavir score.
- BMI >25
- Negative alcohol screen
- Able to understand and willing to voluntarily sign an informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) authorization.
Who cannot join
- Known cardiovascular disease.
- Requiring any of the following medications during the duration of the study:History of cirrhosis based on imaging or clinical criteria and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding.
- History of hepatocellular carcinoma (HCC)
- History of malignancy within the past 5 years or ongoing malignancy other than basal cell carcinoma, or resected noninvasive cutaneous squamous carcinoma at the time of Screening visit.
- Active, serious infections that requires parenteral antibiotic or antifungal therapy within 30 days prior to Screening visit.
- Females who are pregnant or breastfeeding.
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- Current or anticipated treatment with radiation therapy, cytotoxic chemotherapeutic agents and immunomodulating agents (such as systemic corticosteroids, interleukins, interferons).
- Use of any experimental medications within the last 6 months of Screening Visit.
- Familial dyslipidemia Weight loss of >5% within 6 months prior to Screening, based on subject's reporting Currently or participated in a weight loss program within the last 6 months.
- Any history of bariatric surgery Diabetes mellitus Type I.
- Daily alcohol intake >20 ml (2 units)/day for women and 30 ml (3 units)/day for men (on average), as per Alcohol Use Disorders Identification Test (AUDIT) questionnaire at Screening and plan to consume the same alcohol amount referenced above during the trial.
- Use of any immunosuppressive medication, anti-inflammatory monoclonal antibody treatment, or chronic systemic corticosteroids >10 mg prednisone-equivalent concurrently or within 1 year prior to Screening.
- Uncontrolled or clinically unstable thyroid disease, in the judgment of the Principal Investigator.
- History or presence of hepatitis B or C or human immunodeficiency virus (HIV) Uncontrolled arterial hypertension.
- Any severe, acute, or chronic medical or psychiatric condition that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or in compliance with the requirements of the study, or may interfere with the interpretation of study results and, in the investigator's opinion, would make the subject inappropriate for entry into this study.
- Subjects who have previously received imatinib or who have history of hypersensitivity, allergy, intolerance or contraindication to imatinib.
Trial locations and contacts
1 site in 1 country.
Iran1 site
Research Institute of Gastroenterology & Liver Diseases
Tehran, 1985714711
About this study
Official title: A Phase I/II, Randomized, Double-Blind Intervention Trial for Evaluating the Safety and Efficacy of Imatinib in Subjects With Advance Fibrosis
When a recurrent, long-term injury and inflammation of the liver causes an excessive accumulation of damaged tissue, a dangerous condition called liver fibrosis develops. Most chronic liver diseases eventually lead to fibrosis. Activated hepatic stellate cells (aHSC) play an important role in the development of hepatic fibrosis. Inhibiting the proliferation of stellate cells and preventing their differentiation and activation is an ideal strategy for ameliorating hepatic fibrosis. Hence imatinib have been prescribed as a promising drug to limit the progression of liver fibrosis as a clinical inhibitor of tyrosine kinase which can affect the two main pathways leading to hepatic stellate cells activation.
Read the detailed description
Liver fibrosis can be categorized as a serious health problem worldwide. It is widely recognized that activated hepatic stellate cells (HSC) play a pivotal role in pathological development of liver fibrosis. The activated hepatic stellate cells (aHSCs) are main producers of ECM, which play a significant role in scarring process of the liver derived from variety of etiologies, such as hepatitis B or C virus infection, chronic alcohol abuse, non-alcoholic steatohepatitis, cholestasis, and autoimmune hepatitis. Due to lack of effective treatments, chronic liver diseases and liver fibrosis can eventually progress to liver cirrhosis and even liver cancer. Inhibition of the stellate cell proliferation, differentiation and prevention of its activation is appealing as an ideal strategy for ameliorating hepatic fibrosis. A platelet-derived growth factor (PDGF) is the most potent proliferating stimulus for HSC. Imatinib mesylate (Gleevec), a clinically used PDGF receptor (PDGFR) tyrosine kinase inhibitor could be a promising molecular targeted approach to limit the liver fibrosis development. IL-6/STAT3 is one the pivotal signaling pathways for the activation of HSCs. Herein in our previous study we found that Imatinib upregulates miR-124 and interferes simultaneously with STAT3-HLF-IL-6 pathway. However, due to effective role of imatinib in blocking two important liver fibrosis related pathways, pharmacokinetics of imatinib in patients with liver fibrosis have never been assessed. This study is a phase I/II, double blind labeled, randomized, double arms clinical trial. Consequently, this phase I/II trial was initiated to evaluate the safety and efficacy of imatinib in patients with advanced liver fibrosis. 20 patients with clinical and/or pathologic diagnosis of liver fibrosis grade 3-4 will be registered at Taleghani hospital (Tehran). 10 patients will receive standard medication and imatinib for 24 weeks at the dose of 200mg/day orally. Another 10 patients will be treated with standard medication of liver fibrosis and placebo of imatinib drug as a control group.
- Conditions
- Liver Fibrosis
- Being tested
- Imatinib 200mg, Placebo
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib 200mgDrug
Also called Trade name Gleevec or other name STI-571
Imatinib have to be taken 200mg/day orally for 24 weeks in a seated position with a meal or a large (at least 250 mL) glass of water
PlaceboDrug
Capsules (similar appearance with imatinib) without active substance have to be taken orally for 24 weeks in a seated position with a meal or a large (at least 250 mL) glass of water
| Study group | Role | What they receive |
|---|---|---|
| Imatinib Drug | Experimental | Standard medication of liver fibrosis + Imatinib 200 mg 1 time a day. Receives: Drug: Imatinib 200mg |
| Placebo | Placebo comparator | Standard medication of liver fibrosis + placebo as a control group. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of liver fibrosis score changes from baseline to 6 months
by the FibroScan system
Measured: 6 months
Secondary outcomes (11)
Alanine aminotransferase serum levels changes in baseline, 3 months and 6months
Serology testing
Measured: every 3 months for 6 months
Aspartate aminotransferase serum levels changes in baseline, 3 months and 6months
Serology testing
Measured: every 3 months for 6 months
Albumin levels changes in baseline, 3 months and 6months
Serology testing
Measured: every 3 months for 6 months
Bilirubin levels changes in baseline, 3 months and 6months
Serology testing
Measured: every 3 months for 6 months
Detecting changes of Tumor necrosis factor (TNF)-alpha from baseline to 6 months
Serology testing of the serum inflammation markers
Measured: 6 months
Detecting changes of Interleukin-6 from baseline to 6 months
Serology testing of the serum inflammation markers
Measured: 6 months
Blood sugar changes in baseline, 3 months and 6months
Blood test
Measured: every 3 months for 6 months
Fasting insulin changes in baseline, 3 months and 6months
Blood test
Measured: every 3 months for 6 months
Complete blood count changes in baseline, 3 months and 6months
Blood test
Measured: every 3 months for 6 months
International normalized ratio (INR) changes in baseline, 3 months and 6months
Blood test
Measured: every 3 months for 6 months
Prothrombin time (PT) changes in baseline, 3 months and 6months
Blood test
Measured: every 3 months for 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2022
- Study start20 Feb 2021
- Primary completion2 Feb 2022 (estimated)
- Study completion2 Sep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver FibrosisStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Research Institute for Gastroenterology and Liver Diseases (RIGLD)
- Sponsor type
- Research network
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05224128
- Sponsor's protocol ID
- 1112
- Status last verified
- Jan 2022
- First submitted
- 8 Jan 2022
- Last updated
- 4 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Randomized, Double-Blind Intervention Trial for Evaluating the Safety and Efficacy of Imatinib in Subjects With Advance Fibrosis
- ClinicalTrials.gov ID
- NCT05224128
- Acronym / sponsor ID
- 1112
- Conditions
- Liver Fibrosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Research Institute for Gastroenterology and Liver Diseases (RIGLD)Research network
- Study start
- 20 Feb 2021 (actual)
- Primary completion
- 2 Feb 2022 (estimated)
- Study completion
- 2 Sep 2022 (estimated)
- First posted
- 4 Feb 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.
When a recurrent, long-term injury and inflammation of the liver causes an excessive accumulation of damaged tissue, a dangerous condition called liver fibrosis develops. Most chronic liver diseases eventually lead to fibrosis. Activated hepatic stellate cells (aHSC) play an important role in the development of hepatic fibrosis. Inhibiting the proliferation of stellate cells and preventing their differentiation and activation is an ideal strategy for ameliorating hepatic fibrosis. Hence imatinib have been prescribed as a promising drug to limit the progression of liver fibrosis as a clinical inhibitor of tyrosine kinase which can affect the two main pathways leading to hepatic stellate cells activation.
Detailed description
Liver fibrosis can be categorized as a serious health problem worldwide. It is widely recognized that activated hepatic stellate cells (HSC) play a pivotal role in pathological development of liver fibrosis. The activated hepatic stellate cells (aHSCs) are main producers of ECM, which play a significant role in scarring process of the liver derived from variety of etiologies, such as hepatitis B or C virus infection, chronic alcohol abuse, non-alcoholic steatohepatitis, cholestasis, and autoimmune hepatitis. Due to lack of effective treatments, chronic liver diseases and liver fibrosis can eventually progress to liver cirrhosis and even liver cancer. Inhibition of the stellate cell proliferation, differentiation and prevention of its activation is appealing as an ideal strategy for ameliorating hepatic fibrosis. A platelet-derived growth factor (PDGF) is the most potent proliferating stimulus for HSC. Imatinib mesylate (Gleevec), a clinically used PDGF receptor (PDGFR) tyrosine kinase inhibitor could be a promising molecular targeted approach to limit the liver fibrosis development. IL-6/STAT3 is one the pivotal signaling pathways for the activation of HSCs. Herein in our previous study we found that Imatinib upregulates miR-124 and interferes simultaneously with STAT3-HLF-IL-6 pathway. However, due to effective role of imatinib in blocking two important liver fibrosis related pathways, pharmacokinetics of imatinib in patients with liver fibrosis have never been assessed. This study is a phase I/II, double blind labeled, randomized, double arms clinical trial. Consequently, this phase I/II trial was initiated to evaluate the safety and efficacy of imatinib in patients with advanced liver fibrosis. 20 patients with clinical and/or pathologic diagnosis of liver fibrosis grade 3-4 will be registered at Taleghani hospital (Tehran). 10 patients will receive standard medication and imatinib for 24 weeks at the dose of 200mg/day orally. Another 10 patients will be treated with standard medication of liver fibrosis and placebo of imatinib drug as a control group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Imatinib Drug | Experimental | Drug: Imatinib 200mgStandard medication of liver fibrosis + Imatinib 200 mg 1 time a day. |
| Placebo | Placebo comparator | Drug: PlaceboStandard medication of liver fibrosis + placebo as a control group. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males or females between18-75 years old with a clinically confirmed diagnosis of Fibrosis with grade 3-4 by Metavir score.
- BMI >25
- Negative alcohol screen
- Able to understand and willing to voluntarily sign an informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) authorization.
Key exclusion criteria (16 listed)
- Known cardiovascular disease.
- Requiring any of the following medications during the duration of the study:History of cirrhosis based on imaging or clinical criteria and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding.
- History of hepatocellular carcinoma (HCC)
- History of malignancy within the past 5 years or ongoing malignancy other than basal cell carcinoma, or resected noninvasive cutaneous squamous carcinoma at the time of Screening visit.
- Active, serious infections that requires parenteral antibiotic or antifungal therapy within 30 days prior to Screening visit.
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 |
|---|---|---|
| Imatinib 200mgAlso: Trade name Gleevec or other name STI-571Imatinib have to be taken 200mg/day orally for 24 weeks in a seated position with a meal or a large (at least 250 mL) glass of water | Drug | Imatinib Drug |
| PlaceboCapsules (similar appearance with imatinib) without active substance have to be taken orally for 24 weeks in a seated position with a meal or a large (at least 250 mL) glass of water | Drug | Placebo |
Primary outcome
Assessment of liver fibrosis score changes from baseline to 6 months
Time frame: 6 months
by the FibroScan system
11 secondary outcomes
Alanine aminotransferase serum levels changes in baseline, 3 months and 6months
Time frame: every 3 months for 6 months
Aspartate aminotransferase serum levels changes in baseline, 3 months and 6months
Time frame: every 3 months for 6 months
Albumin levels changes in baseline, 3 months and 6months
Time frame: every 3 months for 6 months
Bilirubin levels changes in baseline, 3 months and 6months
Time frame: every 3 months for 6 months
Detecting changes of Tumor necrosis factor (TNF)-alpha from baseline to 6 months
Time frame: 6 months
Detecting changes of Interleukin-6 from baseline to 6 months
Time frame: 6 months
Blood sugar changes in baseline, 3 months and 6months
Time frame: every 3 months for 6 months
Fasting insulin changes in baseline, 3 months and 6months
Time frame: every 3 months for 6 months
Complete blood count changes in baseline, 3 months and 6months
Time frame: every 3 months for 6 months
International normalized ratio (INR) changes in baseline, 3 months and 6months
Time frame: every 3 months for 6 months
Prothrombin time (PT) changes in baseline, 3 months and 6months
Time frame: every 3 months for 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2022.
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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 1/2 study testing Imatinib 200mg in people with Liver Fibrosis, run by Research Institute for Gastroenterology and Liver Diseases (RIGLD) at 1 site in Iran.
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 4 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 4 Feb 2022. 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 Iran. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Assessment of liver fibrosis score changes from baseline to 6 months (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Feb 2022.