Umbilical Cord Mesenchymal Stem Cells for Patients With Autoimmune Hepatitis
Ключови думи
Резюме
Описание
Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory disease of the liver characterized by elevation of IgG, presence of characteristic autoantibodies, and histological feature of interface hepatitis. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. However, current treatment strategies are complicated by frequent relapse after drug withdrawal, medication intolerance, and refractory disease. Alternative medical therapy may be need for AIH.
The potential for stem cells to differentiate into hepatocytes cells was recently confirmed. In particular, bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been applicated in the clinic for treat several human disease such as GVHD, cardiac injury and brain injury, and displayed good tolerance and efficiency. Recently, umbilical cord-derived MSCs (UC-MSC) has also been used to treat severe autoimmune diseases, such as immune thrombocytopenia, systemic lupus erythematosus, and therapy-resistant rheumatoid arthritis.
The purpose of this study is to learn whether and how UC-MSC can improve the disease condition in patients with autoimmune hepatitis (AIH). This study will also look at how well UC-MSC is tolerated and its safety in AIH patients
Participants in the study will be randomly assigned to one of two treatment arms:
Arm A: Participants will receive 12 weeks of UC-MSC treatment plus conventional treatment (combination of corticosteroids and azathioprine) Arm B: Participants will receive 12 weeks of placebo plus conventional treatment. (combination of corticosteroids and azathioprine) UC-MSC will be prepared according to standard procedures and is collected in plastic bags containing anticoagulant. UC-MSCs are given via i.v. under sonography monitoring. After cell therapy, patients are followed up at week 12, 24, 36, 48, 72, 96. The evaluation of some clinical parameters such as the level of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-globulin, total bilirubin (TB), prothrombin time (PT), albumin (ALB), prealbumin (PA) and IgG, are detected at these time points. MELD score, Liver histology, treatment side effects, relapse rate and clinical symptoms were also observed simultaneously.
Дати
| Последна проверка: | 04/30/2013 |
| Първо изпратено: | 08/04/2012 |
| Очаквано записване подадено: | 08/08/2012 |
| Първо публикувано: | 08/09/2012 |
| Изпратена последна актуализация: | 05/29/2013 |
| Последна актуализация публикувана: | 05/30/2013 |
| Действителна начална дата на проучването: | 09/30/2011 |
| Приблизителна дата на първично завършване: | 09/30/2014 |
| Очаквана дата на завършване на проучването: | 09/30/2014 |
Състояние или заболяване
Интервенция / лечение
Other: Conventional plus UC-MSC treatment
Other: Conventional plus placebo treatment
Фаза
Групи за ръце
| Arm | Интервенция / лечение |
|---|---|
| Experimental: Conventional plus UC-MSC treatment Participants will receive conventional treatment plus a dose of UC-MSC from day 0 through the week 12 study visit.
Participants will then be followed until the week 96 study visit. | Other: Conventional plus UC-MSC treatment Received conventional treatment and taken i.v., once per 4 week, at a dose of 1×106 UC-MSC/kg body weight for 12 weeks. |
| Experimental: Conventional plus placebo treatment Participants will receive conventional plus placebo treatment from day 0 through the week 12 study visit. Participants will then be followed until the week 96 study visit. | Other: Conventional plus placebo treatment Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks |
Критерии за допустимост
| Възрасти, отговарящи на условията за проучване | 18 Years Да се 18 Years |
| Полове, допустими за проучване | All |
| Приема здрави доброволци | Да |
| Критерии | Inclusion Criteria: 1. Written informed consent 2. Autoimmune hepatitis (according to the criteria defined by the international autoimmune hepatitis Group ,Hepatology, 2008;48:169-176) 3. Negative pregnancy test (female patients in fertile age) Exclusion Criteria: 1. Hepatocellular carcinoma or other Malignancies 2. Pregnant or lactating women 3. Viral Hepatitis ( HAV,HBV,HCV, et al ) 4. Vital organs failure (Cardiac, Renal or Respiratory, et al) 5. Sepsis 6. Active thrombosis in the portal or hepatic veins |
Резултат
Първични изходни мерки
1. Liver Histology change [baseline and 96 weeks]
2. Serum alanine aminotransferase (ALT) [0,12, 24, 36, 48, 72, 96 weeks after treatment]
Вторични изходни мерки
1. Serum AST [At baseline and at week 12, 24, 36, 48, 72, 96]
2. Serum Tbil [At baseline and at week 12, 24, 36, 48, 72, 96]
3. Serum immunoglobulin G (IgG) [At baseline and at week 12, 24, 36, 48, 72, 96]
4. Serum γ-globulin [At baseline and at week 12, 24, 36, 48, 72, 96]
5. MELD score [At base line and at week 12, 24, 36, 48, 72, 96]
6. Number of participants with treatment side effects [At base line and at week 12, 24, 36, 48, 72, 96]
7. Number of participants with improvement of clinical symptoms [At base line and at week 12, 24, 36, 48, 72, 96]
