Clinical trial NCT05155657: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Alcoholic Cirrhosis
Lead sponsor: Yantai Yuhuangding Hospital
Sponsor class: OTHER
First posted: 2021-12-13
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age 18\~60 years old;
2. 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);
3. The subject was previously diagnosed but treatment is ineffective;
4. Liver function was in child Pugh grade A or MELD score \< 12;
5. Intermittent albumin supplementation and diuretic treatment are required;
6. 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);
7. No history of gastrointestinal hemorrhage in the past month;
8. The subject understand and voluntarily sign the informed consent.

Exclusion Criteria:

1. 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;
2. The subject suffer acute attack of gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome or infection;
3. The subject suffer systemic infection or severe infection during screening;
4. 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;
5. 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;
6. 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.
7. Subject who has received stem cell therapy within 6 months before the screening;
8. Subject who has received biotherapy or participated in other clinical studies within 3 months before screening;
9. 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;
10. 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;
11. Other factors that the researchers believe are not suitable for entering the study.

Primary outcomes:
measure: Severity and incidence of adverse events (SIAE) on the 3rd day after the first administration
timeFrame: The 3rd day after the first administration
measure: 1 week SIAE after the first administration
timeFrame: 1 week after the first administration
measure: 3 weeks SIAE after the first administration
timeFrame: 3 week after the first administration
measure: 3 week SIAE after the the second administration
timeFrame: 3 weeks after the the second administration
measure: 1 month SIAE after the last administration
timeFrame: 1 month after the last administration
measure: 3 months SIAE after the last administration
timeFrame: 3 months after the last administration
measure: 6 months SIAE after the last administration
timeFrame: 6 months after the last administration
measure: 12 months SIAE after the last administration
timeFrame: 12 months after the last administration
measure: 24 months SIAE after the last administration
timeFrame: 24 months after the last administration
Secondary outcomes:
measure: Child-Pugh score (effectiveness evaluation index)
timeFrame: 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.
measure: Survival rate (effectiveness evaluation index)
timeFrame: 12 months after the last administration.
measure: Liver function (effectiveness evaluation index)
timeFrame: 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.
measure: The Model for End-Stage Liver Disease (MELD) score (effectiveness evaluation index)
timeFrame: 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.
measure: KPS score (effectiveness evaluation index)
timeFrame: 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.
measure: Detection of Blood Coagulation Index of PT (effectiveness evaluation index)
timeFrame: 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.
measure: Detection of Blood Coagulation Index of APTT (effectiveness evaluation index)
timeFrame: 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.
measure: Detection of Blood Coagulation Index of TT (effectiveness evaluation index)
timeFrame: 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.
measure: Detection of Blood Coagulation Index of FIB (effectiveness evaluation index)
timeFrame: 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.
Other outcomes:
Locations:
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
Study officials:
affiliation: Yantai Yuhuangding Hospital
name: Jun Cui, MD
role: PRINCIPAL_INVESTIGATOR
References: