Overview
Decompensated cirrhosis has a high overall mortality rate. There is a large unmet need for safe and alternative therapeutic potions. This clinical trial is to inspect the efficiency and safety of mesenchymal stem cells (MSCs) therapy for decompensated cirrhosis.
Description
Decompensated cirrhosis has a high overall mortality rate. Liver transplantation is still the most effective treatment for decompensated cirrhosis. However, the shortage of matched liver sources, high costs, and rejection after liver transplantation restrict the development of liver transplantation.
Mesenchymal stem cells (MSC) are a kind of pluripotent stem cells belonging to mesoderm, which mainly exist in connective tissue and organ interstitium. At present, MSC can be isolated and prepared from bone marrow, fat, synovium, bone, muscle, lung, liver, pancreas and amniotic fluid and umbilical cord blood . Due to its wide range of sources and self-proliferation and differentiation ability, MSCs have therapeutic potential for many diseases, including acute and chronic liver diseases.
In recent years, our team has carried out a series of clinical trials using umbilical cord-derived MSCs to treat patients with end-stage liver disease, decompensated cirrhosis, primary biliary cholangitis, and status after liver transplantation and found that MSCs therapy can significantly improve patient liver function, reduce post-transplantation rejection, reduce complications, improve quality of life, and improve survival. Other investigators have also found in clinical trials with MSCs from different sources that treatment with MSCs can improve MELD scores or liver function levels to varying degrees. However, some studies have found no significant difference between the treatment group and the control group, and MSCs may differentiate into hepatic stellate cells and have the risk of promoting liver fibrosis, it is believed that MSCs do not favor the improvement of liver function in these studies. Therefore, the therapeutic effects of MSCs need to be further validated by larger multicenter randomized controlled clinical trials.
The investigators will do a prospective, double-blind, muliticenter, randomised trial to assess treatment with three intravenous doses of MSCs compared with placebo. 140 decompensated cirrhosis patients will be recruited in China. 70 patients will receive i.v. transfusion 3 times of MSCs and the standard of care as the treated group. In addition, the 70 patients will receive placebo and standard of care as control group.
Eligibility
Inclusion Criteria:
- Patients with a bounded single non-restorable upper tooth in the anterior maxilla (15-25) FDI (El Ebiary et al., 2023b)
- Patients with an age range of 21 to 65 years old (Levine et al., 2022)
- Patients with good oral hygiene with BoP ≤ 10 % (Chapple et al., 2018)
- Compliant patients willing to follow up to one year.
- Remaining labial bone thickness ≥ 1mm measured on C.B.C.T. and confirmed on the day of surgery after tooth extraction and before final implant placement.
Exclusion Criteria:
- The presence of acute/active infection related to the non-restorable tooth (Block et al., 2009) cited in (Soegiantho et al., 2023)
- Presence of labial bone defect as fenestration/dehiscence (Crespi et al., 2008) cited in (Soegiantho et al., 2023)
- Large cyst or pathological lesion related to the tooth (Tallarico et al., 2016-2017) cited in (Soegiantho et al., 2023); (Morton, Wismeijer, Chen, Hamilton, Wittneben, Casentini, Gonzaga, Lazarin, Martin, Molinero-Mourelle, et al., 2023)
- History of radiation to the maxilla (Cannizzaro et al., 2010) cited in (Soegiantho et al., 2023)
- History of bisphosphonate therapy or other anti-resorptive agents (Cannizzaro et al., 2010) cited in (Soegiantho et al., 2023)
- Uncontrolled systemic or metabolic disease. (Cecchinato et al., 2015) cited in (Soegiantho et al., 2023)
- Patients with parafunctional habits or active periodontitis (Cannizzaro et al., 2010) cited in (Soegiantho et al., 2023) 8- Tobacco abuse (\>10 cigarettes per day) (Canullo et al., 2010) cited in (Soegiantho et al., 2023)
9- Alcohol abuse (Block et al., 2009) cited in (Soegiantho et al., 2023)
