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Effect of Mesenchymal Stem Cells-derived Exosomes in Decompensated Liver Cirrhosis

Primary Purpose

Decompensated Liver Cirrhosis

Status
Recruiting
Phase
Phase 2
Locations
Iran, Islamic Republic of
Study Type
Interventional
Intervention
MSC-derived exosomes
Sponsored by
Research Institute for Gastroenterology and Liver Diseases (RIGLD)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Decompensated Liver Cirrhosis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Able to understand and willing to voluntarily sign an informed consent form (ICF) authorization. Males or females between 18-75 years old with a clinically confirmed diagnosis of Liver cirrhosis with any etiology, except viral cirrhosis. Child score class B or C. Exclusion Criteria: Known cardiovascular disease. a) History of hepatocellular carcinoma (HCC). b) 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. c) Active, serious infections that require 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. Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing and protocol requirements. 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. 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 with 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.

Sites / Locations

  • Research Institute of Gastroenterology & Liver DiseasesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Exosome

Arm Description

Standard medication + MSC-derived exosomes at a final dose of 40mg in three weeks

Outcomes

Primary Outcome Measures

Liver function by MELD score
Calculation of MELD score based on patient's laboratory values for serum creatinine, bilirubin, international normalized ratio for prothrombin time, and sodium.
Liver function by MELD score
Calculation of MELD score based on patient's laboratory values for serum creatinine, bilirubin, international normalized ratio for prothrombin time, and sodium.
Liver function by MELD score
Calculation of MELD score based on patient's laboratory values for serum creatinine, bilirubin, international normalized ratio for prothrombin time, and sodium.
Liver function by CHILD score
Calculation of CHILD score based on patient's laboratory values for serum bilirubin, albumin, international normalized ratio for prothrombin time, ascites, and encephalopathy.
Liver function by CHILD score
Calculation of CHILD score based on patient's laboratory values for serum bilirubin, albumin, international normalized ratio for prothrombin time, ascites, and encephalopathy.
Liver function by CHILD score
Calculation of CHILD score based on patient's laboratory values for serum bilirubin, albumin, international normalized ratio for prothrombin time, ascites, and encephalopathy.

Secondary Outcome Measures

Change in liver enzyme AST
Blood test
Change in liver enzyme ALT
Blood test
international normalized ratio (INR) for prothrombin time
Blood test
Bilirubin
Blood test

Full Information

First Posted
April 7, 2023
Last Updated
May 12, 2023
Sponsor
Research Institute for Gastroenterology and Liver Diseases (RIGLD)
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1. Study Identification

Unique Protocol Identification Number
NCT05871463
Brief Title
Effect of Mesenchymal Stem Cells-derived Exosomes in Decompensated Liver Cirrhosis
Official Title
Clinical Trial Phase IIa, on Amelioration of Decompensated Liver Cirrhosis With Mesenchymal Stem Cells-derived Exosomes
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 26, 2023 (Anticipated)
Primary Completion Date
August 11, 2023 (Anticipated)
Study Completion Date
December 11, 2023 (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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. However, little is known about MSC-exosome therapy. We will evaluate the therapeutic potential of mesenchymal stem Cell-Exosomes as an alternative to cell therapy in Cirrhotic patients. This study examined the safety and efficacy of umbilical cord-derived MSC-exosomes in patients with decompensated LC.
Detailed Description
Liver fibrosis is the major cause of morbidity and mortality in patients with liver disorders. Liver fibrosis can be reverted with the removal of the underlying etiology. However, if chronic inflammation and injury persist, liver fibrosis is likely to progress to liver cirrhosis (LC). LC is generally characterized by the formation and accumulation of an extracellular matrix, which lead to the progressive distortion of the hepatic architecture. LC usually progresses irreversibly into a decompensated stage, which is characterized by a series of clinical manifestations, including ascites, variceal hemorrhage, and hepatic encephalopathy, while ascites is the most common clinical symptom in such patients. Although ascites might be treated with diuretics, periodic paracentesis, or a transjugular intrahepatic portosystemic shunt, liver transplantation is the only option that can improve the survival of these patients. However, the severe shortage of donor livers, high costs, and potential serious complications have restricted the availability of liver transplantation worldwide. Therefore, alternative strategies are under intense investigation. Mesenchymal stem cells (MSC) have self-renewal abilities and multidirectional differentiation potentials. They also interact with various types of immune cells, leading to immunomodulation. MSCs have been used therapeutically in clinical trials for graft-versus-host disease and appear to be effective in immune-mediated tissue injury, transplantation, and autoimmunity. In particular, MSCs have also been used to treat liver diseases in animal models and patients. Studies from animal models have shown that bone marrow-derived MSC (BM-MSC) infusion ameliorates liver fibrosis and reverses fulminant hepatic failure. In clinical trials, autologous MSC infusion has been demonstrated to be safe, feasible and can improve the liver function of some LC patients. In addition, BM-MSC from patients with chronic HBV infection suffer from proliferative deficiency and might not be the best choice. In contrast, human umbilical cord-derived MSC (UC-MSC) are free from these limitations related to autologous BM-MSC. In addition, UC-MSC can be obtained from the discarded UC, and therefore, can be produced on a large scale. It has been reported that human UC-MSC infusion can improve liver fibrosis in rats. It has been shown that UC-MSC have potential to be used in clinical scenarios for the treatment of human liver diseases. In the present study, the investigators examine the safety and efficacy of UC-MSC derived exosomes in decompensated LC patients. 15 enrolled patients will receive standard medication plus MSC-derived exosomes at a final dose of 40mg in three weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Decompensated Liver Cirrhosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Exosome
Arm Type
Experimental
Arm Description
Standard medication + MSC-derived exosomes at a final dose of 40mg in three weeks
Intervention Type
Biological
Intervention Name(s)
MSC-derived exosomes
Intervention Description
Patients will receive standard medication plus MSC-derived exosomes at a final dose of 40mg in three weeks. Standard medication includes: a) treatment of the underlying cause of cirrhosis such as drug treatment of hepatitis B and C. b) symptomatic treatment of port complications such as ascites, prevention of variceal bleeding, treatment and prevention of hepatic encephalopathy.
Primary Outcome Measure Information:
Title
Liver function by MELD score
Description
Calculation of MELD score based on patient's laboratory values for serum creatinine, bilirubin, international normalized ratio for prothrombin time, and sodium.
Time Frame
Baseline
Title
Liver function by MELD score
Description
Calculation of MELD score based on patient's laboratory values for serum creatinine, bilirubin, international normalized ratio for prothrombin time, and sodium.
Time Frame
after 2 months of the trial
Title
Liver function by MELD score
Description
Calculation of MELD score based on patient's laboratory values for serum creatinine, bilirubin, international normalized ratio for prothrombin time, and sodium.
Time Frame
after 4 months of the trial
Title
Liver function by CHILD score
Description
Calculation of CHILD score based on patient's laboratory values for serum bilirubin, albumin, international normalized ratio for prothrombin time, ascites, and encephalopathy.
Time Frame
Baseline
Title
Liver function by CHILD score
Description
Calculation of CHILD score based on patient's laboratory values for serum bilirubin, albumin, international normalized ratio for prothrombin time, ascites, and encephalopathy.
Time Frame
after 2 months of the trial
Title
Liver function by CHILD score
Description
Calculation of CHILD score based on patient's laboratory values for serum bilirubin, albumin, international normalized ratio for prothrombin time, ascites, and encephalopathy.
Time Frame
after 4 months of the trial
Secondary Outcome Measure Information:
Title
Change in liver enzyme AST
Description
Blood test
Time Frame
Baseline, after 2 and 4 months of the trial
Title
Change in liver enzyme ALT
Description
Blood test
Time Frame
Baseline, after 2 and 4 months of the trial
Title
international normalized ratio (INR) for prothrombin time
Description
Blood test
Time Frame
Baseline, after 2 and 4 months of the trial
Title
Bilirubin
Description
Blood test
Time Frame
Baseline, after 2 and 4 months of the trial

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: Able to understand and willing to voluntarily sign an informed consent form (ICF) authorization. Males or females between 18-75 years old with a clinically confirmed diagnosis of Liver cirrhosis with any etiology, except viral cirrhosis. Child score class B or C. Exclusion Criteria: Known cardiovascular disease. a) History of hepatocellular carcinoma (HCC). b) 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. c) Active, serious infections that require 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. Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing and protocol requirements. 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. 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 with 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kaveh Baghaei, Ph.D.
Phone
+98 21 2243 2516
Email
kavehbaghai@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Behzad Hatami, MD
Organizational Affiliation
Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti Medical University, Tehran, Iran
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Institute of Gastroenterology & Liver Diseases
City
Tehran
ZIP/Postal Code
1985714711
Country
Iran, Islamic Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kaveh Baghaei, Ph.D.
Phone
+98 21 2243 2516
Email
kavehbaghai@gmail.com
First Name & Middle Initial & Last Name & Degree
Behzad Hatami, MD
First Name & Middle Initial & Last Name & Degree
Kaveh Baghaei, PhD
First Name & Middle Initial & Last Name & Degree
Mohammadreza Zali, MD
First Name & Middle Initial & Last Name & Degree
Taha Aghajanzadeh, MS

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
It is not yet known if there will be a plan to make this available.

Learn more about this trial

Effect of Mesenchymal Stem Cells-derived Exosomes in Decompensated Liver Cirrhosis

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