National Collaborative Centre for Hepatic Regenerative Medicine (NC-CHRM): Phase I Study on Safety and Efficacy of Mesenchymal Stem-Cell (MSC) Therapy in Non-Viral Acute-on-Chronic Liver Failure (ACLF)

Официальное название

National Collaborative Centre for Hepatic Regenerative Medicine (NC-CHRM): To Study the Safety and Efficacy of Mesenchymal Stem-Cell Therapy in the Management of Non-viral ACLF Patients: Phase-I Clinical Study

Обзор

Liver disease deaths are rising, but transplants remain scarce in India. With over 100,000 needed annually and only \~2,500 performed, non-transplant options are urgently needed. Regenerative therapy, especially MSCs, shows promise but lacks validation, particularly for non-viral Acute on Chronic Liver Failure (ACLF). The proposed NC-CHRM aims to develop and validate MSC-based therapy to promote native liver regeneration and offer a safe, effective, transplant-free treatment.

Подробное описание

The incidence of deaths from chronic liver diseases (CLD) and cirrhosis are rapidly increasing globally, including India. Liver transplant is the only curative option. Unfortunately, transplant is often not feasible. There is a need for nearly 100,000 liver transplants every year in India, though, only about 2,500 transplants are being done at present across the country. There is therefore, a huge unmet need of developing non-transplant options for chronic liver disease patients. In this regard emerging science of regenerative therapy holds great promises but therapeutic benefit of these therapies is limited due to lack of clinical validation.

Novelty: Liver failure is failure of regeneration hence, potentiating native liver repair and regeneration can serve as potential non-transplant approaches. Others and the investigators have shown in experimental studies that mesenchymal stem cells (MSCs) can improve hepatic regeneration. MSC therapy trials in decompensated cirrhosis and viral ACLF in Korea, China and Japan have shown promise but their utility in non-viral ACLF is limited. In the proposed National Collaborative Centre for Hepatic Regenerative Medicine (NC-CHRM) the investigators will use this novel regenerative medicine approaches MSC for management of acute liver failure in non-viral ACLF to develop safe and effective regenerative therapy clinical protocol for transplant free management of liver failure in cirrhosis. Using integrated cellular, molecular and functional analysis the investigators will also establish their mechanism of action and identify biomarker to access therapeutic response.

Вмешательства

• Препарат umbilical cord Mesenchymal Stem Cell
  To test the safety and tolerability of ucMSC 1 million/kg will be given intra-venously once a week for 4 week in 10 ACLF patients. 250 ml normal saline will be infused 30 minutes prior to ucMSCs infusion. The fresh ucMSCs will be taken from ILBS cGMP facility and will be infused through IV canula peripherally over 30 minutes followed by a further 250 ml normal saline over 20-30 minutes.

Первичные конечные точки

• Safety of ucMSC infusion in non-viral ACLF patients defined as proportion of patients completing the protocolized doses of MSC without major adverse effects requiring discontinuation. [Срок оценки: Day 28 and Day 90]

Вторичные конечные точки (4)

• Proportion of patients developing minor adverse effects [Срок оценки: Day 28 and Day 90]
• Feasibility of ucMSC isolation and therapy Improvement in APASL ACLF Research Consortium (AARC) and MELD score from baseline at day 28 and day 90 [Срок оценки: Day 28 and day 90]
• Incidence of sepsis (assessed by positive culture reports) [Срок оценки: Day 28 and Day 90]
• Incidence of renal dysfunction (evaluated by urine output and kidney function tests [KFTs]) [Срок оценки: Day 28 and 90]

Критерии участия

Критерии включения

• ACLF patients with Model for End-Stage Liver Disease (MELD) >18 or APASL ACLF Research Consortium (AARC) grade 2 or more with (no or single extrahepatic organ dysfunction or failure having no option of liver transplant).

Критерии исключения

• Age <18 or >65 yrs
• Patients with active sepsis
• Patients with hepatic venous outflow tract obstruction (HVOTO) or Extrahepatic portal vein obstruction (EHPVO)
• Hepatocellular carcinoma (beyond Milan) or any extrahepatic malignancy
• Active bleed (mucosal or variceal) or severe coagulopathy (platelets <20,000 or INR>4)
• Patients with refractory shock requiring norepinephrine >0.5ug/kg/min
• Patients with severe Acute Respiratory Distress Syndrome (ARDS) with Pa02/Fi02 <150
• Patients with retroviral infections
• Autoimmune hepatitis
• Viral etiology of liver disease
• Co-existent Hepatitis B, Hepatitis C, HIV
• Chronic kidney disease
• Multiorgan failure or disseminated intravascular coagulation (DIC)
• Patients improving on standard medical treatment
• Patients on immunosuppressive medications
• Pregnancy or active breastfeeding
• Known severe cardiopulmonary diseases (structural or valvular heart disease, coronary artery disease, coronary pulmonary disease, chronic kidney disease)
• Lack of informed consent

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07131540 · ILBS-ACLF-70

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗