Decompensated Liver CirrhosisPhase 2NCT05871463
Effect of Mesenchymal Stem Cells-derived Exosomes in Decompensated Liver Cirrhosis
A Phase 2 study testing MSC-derived exosomes in people with Decompensated Liver Cirrhosis, run by Research Institute for Gastroenterology and Liver Diseases (RIGLD) at 1 site in Iran.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Decompensated Liver Cirrhosis
- What is being tested?
- MSC-derived exosomes
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteIran
- Study dates
- 26 May 2023to 11 Dec 2023
- Phase
- Phase 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
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Iran1 site, 1 recruiting
- Recruiting
Research Institute of Gastroenterology & Liver Diseases
Tehran, 1985714711
Kaveh Baghaei, Ph.D., +98 21 2243 2516, kavehbaghai@gmail.com
Behzad Hatami, MD
About this study
Official title: Clinical Trial Phase IIa, on Amelioration of Decompensated Liver Cirrhosis With Mesenchymal Stem Cells-derived Exosomes
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.
Read the 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.
- Conditions
- Decompensated Liver Cirrhosis
- Being tested
- MSC-derived exosomes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSC-derived exosomesBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Exosome | Experimental | Standard medication + MSC-derived exosomes at a final dose of 40mg in three weeks Receives: Biological: MSC-derived exosomes |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline
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.
Measured: after 2 months of the trial
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.
Measured: after 4 months of the trial
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.
Measured: Baseline
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.
Measured: after 2 months of the trial
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.
Measured: after 4 months of the trial
Secondary outcomes (4)
Change in liver enzyme AST
Blood test
Measured: Baseline, after 2 and 4 months of the trial
Change in liver enzyme ALT
Blood test
Measured: Baseline, after 2 and 4 months of the trial
international normalized ratio (INR) for prothrombin time
Blood test
Measured: Baseline, after 2 and 4 months of the trial
Bilirubin
Blood test
Measured: Baseline, after 2 and 4 months of the trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2023
- Study start26 May 2023 (estimated)
- Primary completion11 Aug 2023 (estimated)
- Study completion11 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Decompensated Liver CirrhosisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Research Institute for Gastroenterology and Liver Diseases (RIGLD)
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Behzad Hatami, MD, Principal investigator, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti Medical University, Tehran, Iran
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05871463
- Sponsor's protocol ID
- 1208
- Status last verified
- May 2023
- First submitted
- 7 Apr 2023
- Last updated
- 23 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It is not yet known if there will be a plan to make this available.
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial Phase IIa, on Amelioration of Decompensated Liver Cirrhosis With Mesenchymal Stem Cells-derived Exosomes
- ClinicalTrials.gov ID
- NCT05871463
- Acronym / sponsor ID
- 1208
- Conditions
- Decompensated Liver Cirrhosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Research Institute for Gastroenterology and Liver Diseases (RIGLD)Research network
- Study start
- 26 May 2023 (estimated)
- Primary completion
- 11 Aug 2023 (estimated)
- Study completion
- 11 Dec 2023 (estimated)
- First posted
- 23 May 2023 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Exosome | Experimental | Biological: MSC-derived exosomesStandard medication + MSC-derived exosomes at a final dose of 40mg in three weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
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 |
|---|---|---|
| MSC-derived exosomesPatients 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. | Biological | Exosome |
Primary outcome
Liver function by MELD score
Time frame: Baseline
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
Time frame: after 2 months of the trial
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
Time frame: after 4 months of the trial
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
Time frame: Baseline
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
Time frame: after 2 months of the trial
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
Time frame: after 4 months of the trial
Calculation of CHILD score based on patient's laboratory values for serum bilirubin, albumin, international normalized ratio for prothrombin time, ascites, and encephalopathy.
4 secondary outcomes
Change in liver enzyme AST
Time frame: Baseline, after 2 and 4 months of the trial
Change in liver enzyme ALT
Time frame: Baseline, after 2 and 4 months of the trial
international normalized ratio (INR) for prothrombin time
Time frame: Baseline, after 2 and 4 months of the trial
Bilirubin
Time frame: Baseline, after 2 and 4 months of the trial
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2023.
- Individual participant dataSharing planned: Undecided. It is not yet known if there will be a plan to make this available.
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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.
Behzad Hatami, MD principal investigator
Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti Medical University, Tehran, Iran
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MSC-derived exosomes in people with Decompensated Liver Cirrhosis, 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 3 inclusion and 15 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 23 May 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 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. 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 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?
Contact Kaveh Baghaei, Ph.D. (+98 21 2243 2516, kavehbaghai@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liver function by MELD score (time frame: Baseline). 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?
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 23 May 2023.