Back to resultsStudy of Decompensated Alcoholic Cirrhosis Treatment by Stem Cells
Primary Purpose
Alcoholic Cirrhosis
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Conventional therapy plus low dose UCMSCs treatment
Conventional therapy plus medium dose UCMSCs treatment
Conventional therapy plus high dose UCMSCs treatment
Sponsored by
About this trial
This is an interventional treatment trial for Alcoholic Cirrhosis
Eligibility Criteria
Inclusion Criteria:
- Age 18~60 years old;
- The subject was diagnosed as decompensated alcoholic liver cirrhosis, according to the Guidelines for the Diagnosis and Treatment of Liver Cirrhosis and the Guidelines for the Prevention and Treatment of Alcoholic Liver Disease (2018);
- The subject was previously diagnosed but treatment is ineffective;
- Liver function was in child Pugh grade A or MELD score < 12;
- Intermittent albumin supplementation and diuretic treatment are required;
- The subject's Albumin level is less than 35g/L, total bilirubin is smaller than 10 times of the upper limit of normal value (hepatocyte hepatitis), or smaller than 15 times of the upper limit of normal value (cholestatic hepatitis or hepatocyte combined with cholestatic hepatitis), prothrombin activity is over 40% (grade II or lower hepatic encephalopathy has been controlled);
- No history of gastrointestinal hemorrhage in the past month;
- The subject understand and voluntarily sign the informed consent.
Exclusion Criteria:
- The subject is allergic physique, with a history of drug or food allergies, especially those who are allergic to umbilical cord mesenchymal stem cells and any components in excipients;
- The subject suffer acute attack of gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome or infection;
- The subject suffer systemic infection or severe infection during screening;
- Abnormal laboratory examinations results, including blood routine: peripheral blood white blood cell count <2.0×10^9/L or >12×10^9/L, hemoglobin (Hb) is less than 70% lower limit of the normal value, platelets <50×10^9/L ; Liver function: ALT or AST> 5 times the upper limit of normal; Renal function: Serum Creatinine (sCr)> 1.5 times the upper limit of normal; in case of abnormality, test shall be repeated;
- Those who were positive for Hepatitis B surface Antigen (HBsAg) or Hepatitis C virus (HCV) antibody, Human Immunodeficiency Virus (HIV) antibody or syphilis antibody during screening;
- Subjects suffer from serious, progressive, or uncontrolled diseases of important organs (including cardiovascular system, liver, lung and kidney), and other autoimmune diseases, malignant tumors, or a history of previous tumors, as well as other diseases that researchers believe that they are not suitable to participate in this clinical study.
- Subject who has received stem cell therapy within 6 months before the screening;
- Subject who has received biotherapy or participated in other clinical studies within 3 months before screening;
- Female subjects who are pregnant, lactating, or premenopausal subject who failed to take medically approved non-drug contraceptive measures (such as intrauterine device, condom, female sterilization) during treatment and within 6 months after the treatment; or have a pregnancy plan within 6 months after the end of the study;
- Male subjects who fail to take medically approved non-drug contraceptive measures (such as male sterilization or condom) during the treatment period and within 6 months after the end of the treatment;
- Other factors that the researchers believe are not suitable for entering the study.
Sites / Locations
- Yantai Yuhuangding HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Low dose umbilical cord mesenchymal stem cells (UCMSCs)
Medium dose UCMSCs
High dose UCMSCs
Arm Description
Outcomes
Primary Outcome Measures
Severity and incidence of adverse events (SIAE) on the 3rd day after the first administration
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
1 week SIAE after the first administration
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
3 weeks SIAE after the first administration
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
3 week SIAE after the the second administration
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
1 month SIAE after the last administration
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
3 months SIAE after the last administration
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
6 months SIAE after the last administration
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
12 months SIAE after the last administration
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
24 months SIAE after the last administration
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
Secondary Outcome Measures
Child-Pugh score (effectiveness evaluation index)
The Child-Pugh grading standard is a grading standard commonly used in clinical practice to quantitatively evaluate the liver reserve function of patients with liver cirrhosis. Grading: 5~6 points for Grade A, 7~9 points for Grade B and 10~15 points for grade C;
Note:
For Primary Biliary Cirrhosis (PBC) or Primary Sclerosing Cholangitis (PSC): total bilirubin (umol/L): 17~68 is 1 point, 68~170 is 1 point, and >170 is 1 point; The Child-Pugh grading standard has been widely recognized by clinicians, and provides a specific clinical reference for the selection of treatment options for patients with liver cirrhosis and has important clinical value.
Survival rate (effectiveness evaluation index)
Overall survival rate of participants in this study.
Liver function (effectiveness evaluation index)
Indicators: Alanine transaminase (AST), Alanine transaminase (ALT)
The Model for End-Stage Liver Disease (MELD) score (effectiveness evaluation index)
MELD is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill), used for liver transplant candidates age 12 and older. It gives each person a 'score' (number) based on how urgently he or she needs a liver transplant within the next three months.
The number is calculated by a formula using three routine lab test results:
MELD score = 3.8×ln[bilirubin (mg/dl)] + 11.2×ln(INR) + 9.6×ln[Scr(mg/dl)] + 6.4×(Cause: Bile or alcoholic 0, other 1) Bilirubin (mg/dl) = Bilirubin (μmol/L)/17.1 Scr(mg/dl) = Scr(μmol/L)/88.4
KPS score (effectiveness evaluation index)
KPS score is the Karnofsky (Karen, KPS, percentile method) functional status scoring standard. The higher the score, the better the health status, and the more the patient able to tolerate the side effects of treatment, hence a better curative effect. It is generally believed that a Karnofsky score above 80 is independent, which means the patient is able to take care of himself. Karnofsky score between 50 to 70 stands for a semi-independent status, that is, the patient is semi-self-care. A score of 50 means the patients require help from others. Those with a score greater than 80 are in better postoperative state and have a longer survival period.
The lower the score, the worse the health status. If the score is less than 60, many effective anti-tumor treatments cannot be implemented.
Detection of Blood Coagulation Index of PT (effectiveness evaluation index)
To test the blood coagulation index of Prothrombin time (PT);
Detection of Blood Coagulation Index of APTT (effectiveness evaluation index)
To test the blood coagulation index of activated partial thromboplastin time (APTT);
Detection of Blood Coagulation Index of TT (effectiveness evaluation index)
To test the blood coagulation index of thrombin time (TT);
Detection of Blood Coagulation Index of FIB (effectiveness evaluation index)
To test the blood coagulation index of fibrinogen (FIB);
Full Information
NCT ID
NCT05155657
First Posted
November 19, 2021
Last Updated
March 26, 2023
Sponsor
Yantai Yuhuangding Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05155657
Brief Title
Study of Decompensated Alcoholic Cirrhosis Treatment by Stem Cells
Official Title
A Pilot Clinical Study to Evaluate Safety, Tolerability and Preliminary Efficacy of Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cell in the Treatment of Decompensated Alcoholic Cirrhosis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 13, 2022 (Actual)
Primary Completion Date
December 25, 2024 (Anticipated)
Study Completion Date
December 25, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yantai Yuhuangding Hospital
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
The main purpose of this study is to evaluate the safety and tolerance of umbilical cord mesenchymal stem cells (UCMSCs) in patients with decompensated alcoholic cirrhosis, and to provide dose basis for subsequent clinical study design. We will also explore the possible mechanism of UCMSCs in the treatment of decompensated alcoholic cirrhosis (DAC).
Detailed Description
This study adopted a single-center, single-arm, single-dose combined multiple-dose administration, and dose-escalation clinical trial design to evaluate the safety, tolerability and preliminary effectiveness of UCMSCs in the treatment of patients with decompensated liver cirrhosis. Patients were recruited into three different dose groups, and 12 subjects were enrolled in each group. The subjects of each group will receive 0.5×10^6 cells/kg, 1.0×10^6 cells/kg, and 2.0×10^6 cells/kg respectively. According to the principle of dose escalation, subjects preset to low-dose will receive the administration first. Each group will receive only one corresponding dose for safety and tolerability check. The subjects will be observed for 21 days after the initial dose due to limited proliferation or differentiation potential and relatively low immunogenicity of mesenchymal stem cell products. The safety measures will be discussed by the Data Safety and Monitoring Board (DSMB) to determine whether subjects who have received a single dose will proceed with subsequent injections. Once all subjects in the lower-dose group have completed the initial administration and observed for 21 days. The DSMB will decided whether to proceed with the next-dose group. All subjects will receive routine drug treatment during the study. Primary endpoint: incidence and severity of cell therapy related adverse events from the beginning of treatment to the end of the follow-up. Secondary end point of the study includes: the change in Model For End-Stage Liver Disease (MELD) score of the subjects from baseline, at 1, 3, 6 and 12 months after the last administration; the overall survival rate at the 12th month after the last administration; Changes in liver function compared with baseline at 1, 3, 6 and 12 months after the last administration; changes of child Pugh score compared with baseline at 1, 3, 6 and 12 months after the last administration; and the change of Karnofsky Performance Status Scale (KPS) score from baseline at 1, 3, 6 and 12 months after the last administration.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholic Cirrhosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
Outcomes Assessor
Allocation
Non-Randomized
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Low dose umbilical cord mesenchymal stem cells (UCMSCs)
Arm Type
Experimental
Arm Title
Medium dose UCMSCs
Arm Type
Experimental
Arm Title
High dose UCMSCs
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Conventional therapy plus low dose UCMSCs treatment
Intervention Description
Patients will receive the conventional therapy plus low dose UCMSCs treatment (0.5×10^6 UCMSCs/kg body)
Intervention Type
Biological
Intervention Name(s)
Conventional therapy plus medium dose UCMSCs treatment
Intervention Description
Patients will receive conventional therapy plus medium dose UCMSCs treatment (1×10^6 UCMSCs/kg body)
Intervention Type
Biological
Intervention Name(s)
Conventional therapy plus high dose UCMSCs treatment
Intervention Description
Patients will receive conventional therapy plus high dose UCMSCs treatment (2×10^6 UCMSCs/kg body)
Primary Outcome Measure Information:
Title
Severity and incidence of adverse events (SIAE) on the 3rd day after the first administration
Description
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
Time Frame
The 3rd day after the first administration
Title
1 week SIAE after the first administration
Description
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
Time Frame
1 week after the first administration
Title
3 weeks SIAE after the first administration
Description
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
Time Frame
3 week after the first administration
Title
3 week SIAE after the the second administration
Description
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
Time Frame
3 weeks after the the second administration
Title
1 month SIAE after the last administration
Description
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
Time Frame
1 month after the last administration
Title
3 months SIAE after the last administration
Description
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
Time Frame
3 months after the last administration
Title
6 months SIAE after the last administration
Description
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
Time Frame
6 months after the last administration
Title
12 months SIAE after the last administration
Description
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
Time Frame
12 months after the last administration
Title
24 months SIAE after the last administration
Description
According to the evaluation criteria of common adverse events (CTCAE v5.0), any AE occurred in all subjects during the clinical study, including abnormalities in clinical symptoms and vital signs and abnormalities in laboratory examination was observed.
Time Frame
24 months after the last administration
Secondary Outcome Measure Information:
Title
Child-Pugh score (effectiveness evaluation index)
Description
The Child-Pugh grading standard is a grading standard commonly used in clinical practice to quantitatively evaluate the liver reserve function of patients with liver cirrhosis. Grading: 5~6 points for Grade A, 7~9 points for Grade B and 10~15 points for grade C;
Note:
For Primary Biliary Cirrhosis (PBC) or Primary Sclerosing Cholangitis (PSC): total bilirubin (umol/L): 17~68 is 1 point, 68~170 is 1 point, and >170 is 1 point; The Child-Pugh grading standard has been widely recognized by clinicians, and provides a specific clinical reference for the selection of treatment options for patients with liver cirrhosis and has important clinical value.
Time Frame
At baseline, 3, 7 and 21 days after the first administration, 21 days after the second administration (if any), and 1, 3, 6 and 12 months after the last administration.
Title
Survival rate (effectiveness evaluation index)
Description
Overall survival rate of participants in this study.
Time Frame
12 months after the last administration.
Title
Liver function (effectiveness evaluation index)
Description
Indicators: Alanine transaminase (AST), Alanine transaminase (ALT)
Time Frame
Baseline, 3, 7, and 21 days after the first administration, 21 days after the second administration (if any), and 1, 3, 6, and 12 months after the last administration.
Title
The Model for End-Stage Liver Disease (MELD) score (effectiveness evaluation index)
Description
MELD is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill), used for liver transplant candidates age 12 and older. It gives each person a 'score' (number) based on how urgently he or she needs a liver transplant within the next three months.
The number is calculated by a formula using three routine lab test results:
MELD score = 3.8×ln[bilirubin (mg/dl)] + 11.2×ln(INR) + 9.6×ln[Scr(mg/dl)] + 6.4×(Cause: Bile or alcoholic 0, other 1) Bilirubin (mg/dl) = Bilirubin (μmol/L)/17.1 Scr(mg/dl) = Scr(μmol/L)/88.4
Time Frame
Baseline, 3, 7, and 21 days after the first administration, 21 days after the second administration (if any), and 1, 3, 6, and 12 months after the last administration.
Title
KPS score (effectiveness evaluation index)
Description
KPS score is the Karnofsky (Karen, KPS, percentile method) functional status scoring standard. The higher the score, the better the health status, and the more the patient able to tolerate the side effects of treatment, hence a better curative effect. It is generally believed that a Karnofsky score above 80 is independent, which means the patient is able to take care of himself. Karnofsky score between 50 to 70 stands for a semi-independent status, that is, the patient is semi-self-care. A score of 50 means the patients require help from others. Those with a score greater than 80 are in better postoperative state and have a longer survival period.
The lower the score, the worse the health status. If the score is less than 60, many effective anti-tumor treatments cannot be implemented.
Time Frame
Baseline, 3, 7, and 21 days after the first administration, 21 days after the second administration (if any), and 1, 3, 6, and 12 months after the last administration.
Title
Detection of Blood Coagulation Index of PT (effectiveness evaluation index)
Description
To test the blood coagulation index of Prothrombin time (PT);
Time Frame
Baseline, 3, 7, and 21 days after the first administration, 21 days after the second administration (if any), and 1, 3, 6, and 12 months after the last administration.
Title
Detection of Blood Coagulation Index of APTT (effectiveness evaluation index)
Description
To test the blood coagulation index of activated partial thromboplastin time (APTT);
Time Frame
Baseline, 3, 7, and 21 days after the first administration, 21 days after the second administration (if any), and 1, 3, 6, and 12 months after the last administration.
Title
Detection of Blood Coagulation Index of TT (effectiveness evaluation index)
Description
To test the blood coagulation index of thrombin time (TT);
Time Frame
Baseline, 3, 7, and 21 days after the first administration, 21 days after the second administration (if any), and 1, 3, 6, and 12 months after the last administration.
Title
Detection of Blood Coagulation Index of FIB (effectiveness evaluation index)
Description
To test the blood coagulation index of fibrinogen (FIB);
Time Frame
Baseline, 3, 7, and 21 days after the first administration, 21 days after the second administration (if any), and 1, 3, 6, and 12 months after the last administration.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18~60 years old;
The subject was diagnosed as decompensated alcoholic liver cirrhosis, according to the Guidelines for the Diagnosis and Treatment of Liver Cirrhosis and the Guidelines for the Prevention and Treatment of Alcoholic Liver Disease (2018);
The subject was previously diagnosed but treatment is ineffective;
Liver function was in child Pugh grade A or MELD score < 12;
Intermittent albumin supplementation and diuretic treatment are required;
The subject's Albumin level is less than 35g/L, total bilirubin is smaller than 10 times of the upper limit of normal value (hepatocyte hepatitis), or smaller than 15 times of the upper limit of normal value (cholestatic hepatitis or hepatocyte combined with cholestatic hepatitis), prothrombin activity is over 40% (grade II or lower hepatic encephalopathy has been controlled);
No history of gastrointestinal hemorrhage in the past month;
The subject understand and voluntarily sign the informed consent.
Exclusion Criteria:
The subject is allergic physique, with a history of drug or food allergies, especially those who are allergic to umbilical cord mesenchymal stem cells and any components in excipients;
The subject suffer acute attack of gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome or infection;
The subject suffer systemic infection or severe infection during screening;
Abnormal laboratory examinations results, including blood routine: peripheral blood white blood cell count <2.0×10^9/L or >12×10^9/L, hemoglobin (Hb) is less than 70% lower limit of the normal value, platelets <50×10^9/L ; Liver function: ALT or AST> 5 times the upper limit of normal; Renal function: Serum Creatinine (sCr)> 1.5 times the upper limit of normal; in case of abnormality, test shall be repeated;
Those who were positive for Hepatitis B surface Antigen (HBsAg) or Hepatitis C virus (HCV) antibody, Human Immunodeficiency Virus (HIV) antibody or syphilis antibody during screening;
Subjects suffer from serious, progressive, or uncontrolled diseases of important organs (including cardiovascular system, liver, lung and kidney), and other autoimmune diseases, malignant tumors, or a history of previous tumors, as well as other diseases that researchers believe that they are not suitable to participate in this clinical study.
Subject who has received stem cell therapy within 6 months before the screening;
Subject who has received biotherapy or participated in other clinical studies within 3 months before screening;
Female subjects who are pregnant, lactating, or premenopausal subject who failed to take medically approved non-drug contraceptive measures (such as intrauterine device, condom, female sterilization) during treatment and within 6 months after the treatment; or have a pregnancy plan within 6 months after the end of the study;
Male subjects who fail to take medically approved non-drug contraceptive measures (such as male sterilization or condom) during the treatment period and within 6 months after the end of the treatment;
Other factors that the researchers believe are not suitable for entering the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jun Cui, MD
Phone
86 05356691999
Ext
82730
Email
cuijun89@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Peiwen Lian, PhD
Phone
86 05356691999
Ext
82708
Email
lianpeiwen@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun Cui, MD
Organizational Affiliation
Yantai Yuhuangding Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yantai Yuhuangding Hospital
City
Yantai
State/Province
Shandong
ZIP/Postal Code
264000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Cui, MD
Phone
86 05356691999
Ext
82730
Email
cuijun89@163.com
First Name & Middle Initial & Last Name & Degree
Peiwen Lian, PhD
Phone
86 05356691999
Ext
82708
Email
lianpeiwen@.qqcom
12. IPD Sharing Statement
Learn more about this trial
Study of Decompensated Alcoholic Cirrhosis Treatment by Stem Cells
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