Back to resultsEffect of Imatinib in Advance Liver Fibrosis Patients
Primary Purpose
Liver Fibrosis
Status
Active
Phase
Phase 1
Locations
Iran, Islamic Republic of
Study Type
Interventional
Intervention
Imatinib 200mg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Liver Fibrosis
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
Sites / Locations
- Research Institute of Gastroenterology & Liver Diseases
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Imatinib Drug
Placebo
Arm Description
Standard medication of liver fibrosis + Imatinib 200 mg 1 time a day.
Standard medication of liver fibrosis + placebo as a control group.
Outcomes
Primary Outcome Measures
Assessment of liver fibrosis score changes from baseline to 6 months
by the FibroScan system
Secondary Outcome Measures
Alanine aminotransferase serum levels changes in baseline, 3 months and 6months
Serology testing
Aspartate aminotransferase serum levels changes in baseline, 3 months and 6months
Serology testing
Albumin levels changes in baseline, 3 months and 6months
Serology testing
Bilirubin levels changes in baseline, 3 months and 6months
Serology testing
Detecting changes of Tumor necrosis factor (TNF)-alpha from baseline to 6 months
Serology testing of the serum inflammation markers
Detecting changes of Interleukin-6 from baseline to 6 months
Serology testing of the serum inflammation markers
Blood sugar changes in baseline, 3 months and 6months
Blood test
Fasting insulin changes in baseline, 3 months and 6months
Blood test
Complete blood count changes in baseline, 3 months and 6months
Blood test
International normalized ratio (INR) changes in baseline, 3 months and 6months
Blood test
Prothrombin time (PT) changes in baseline, 3 months and 6months
Blood test
Full Information
NCT ID
NCT05224128
First Posted
January 8, 2022
Last Updated
January 24, 2022
Sponsor
Research Institute for Gastroenterology and Liver Diseases (RIGLD)
1. Study Identification
Unique Protocol Identification Number
NCT05224128
Brief Title
Effect of Imatinib in Advance Liver Fibrosis Patients
Official Title
A Phase I/II, Randomized, Double-Blind Intervention Trial for Evaluating the Safety and Efficacy of Imatinib in Subjects With Advance Fibrosis
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 20, 2021 (Actual)
Primary Completion Date
February 2, 2022 (Anticipated)
Study Completion Date
September 2, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Research Institute for Gastroenterology and Liver Diseases (RIGLD)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Imatinib Drug
Arm Type
Experimental
Arm Description
Standard medication of liver fibrosis + Imatinib 200 mg 1 time a day.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Standard medication of liver fibrosis + placebo as a control group.
Intervention Type
Drug
Intervention Name(s)
Imatinib 200mg
Other Intervention Name(s)
Trade name Gleevec or other name STI-571
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Assessment of liver fibrosis score changes from baseline to 6 months
Description
by the FibroScan system
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Alanine aminotransferase serum levels changes in baseline, 3 months and 6months
Description
Serology testing
Time Frame
every 3 months for 6 months
Title
Aspartate aminotransferase serum levels changes in baseline, 3 months and 6months
Description
Serology testing
Time Frame
every 3 months for 6 months
Title
Albumin levels changes in baseline, 3 months and 6months
Description
Serology testing
Time Frame
every 3 months for 6 months
Title
Bilirubin levels changes in baseline, 3 months and 6months
Description
Serology testing
Time Frame
every 3 months for 6 months
Title
Detecting changes of Tumor necrosis factor (TNF)-alpha from baseline to 6 months
Description
Serology testing of the serum inflammation markers
Time Frame
6 months
Title
Detecting changes of Interleukin-6 from baseline to 6 months
Description
Serology testing of the serum inflammation markers
Time Frame
6 months
Title
Blood sugar changes in baseline, 3 months and 6months
Description
Blood test
Time Frame
every 3 months for 6 months
Title
Fasting insulin changes in baseline, 3 months and 6months
Description
Blood test
Time Frame
every 3 months for 6 months
Title
Complete blood count changes in baseline, 3 months and 6months
Description
Blood test
Time Frame
every 3 months for 6 months
Title
International normalized ratio (INR) changes in baseline, 3 months and 6months
Description
Blood test
Time Frame
every 3 months for 6 months
Title
Prothrombin time (PT) changes in baseline, 3 months and 6months
Description
Blood test
Time Frame
every 3 months for 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
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.
Facility Information:
Facility Name
Research Institute of Gastroenterology & Liver Diseases
City
Tehran
ZIP/Postal Code
1985714711
Country
Iran, Islamic Republic of
12. IPD Sharing Statement
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Effect of Imatinib in Advance Liver Fibrosis Patients
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