A Phase 1b, Open Label, Uncontrolled, Non-randomized Dose-escalation Study to Examine the Safety of Intramuscular Autologous Transplantation of Escalating Doses of Mesenchymal Stem Cells to Patients With no Option Critical Limb Ischemia.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- The number of Serious Adverse Events that are attributable to the treatment
研究概览
简要总结
The trial is a phase 1b, open label, uncontrolled, non-randomized dose-escalation study of autologous bone marrow-derived MSCs. Following informed consent, patients who meet the criteria will be screened and enrolled. Up to 100 mls of bone marrow will be harvested from the participant from which MSCs will be culture expanded. In this dose escalation study, 3 participants on each cohort will be treated with a targeted dose of either 20 million hMSC; 40 million hMSC; or 80 million hMSC. The cells will be administered to the ischemic leg by 20 intramuscular injections of approximately 0.5ml per injection . Treatment groups will be completed sequentially, beginning with the lowest dose group.
详细描述
This is a phase 1b, open label, uncontrolled, non-randomized dose-escalation study to examine the safety of intramuscular autologous transplantation of escalating doses of mesenchymal stem cells to patients with no option critical limb ischemia.
Trial Aims and Objectives: To examine the safety of intramuscular transplantation of escalating doses of autologous bone marrow derived mesenchymal stem cells to patients with no option critical limb ischemia.
Patient Population: Patients with critical limb ischemia who are not candidates for revascularization.
Trial Setting:HRB Clinical Research Facility Galway and Galway University Hospitals.
Trial Intervention:Intramuscular delivery of autologous bone marrow-derived mesenchymal stem cells to patients with no option critical limb ischemia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Each patient must meet all of the following inclusion criteria to be enrolled into the study
- •Men and women between the ages of 18 and 85
- •Voluntary written informed consent, given before performance of any study-related procedure not part of standard medical care, and with the understanding that consent may be withdrawn at any time without prejudice to future medical care
- •Presented with CLI with rest pain or ulceration with no option for revascularization agreed by an expert panel including an interventional radiologist and vascular surgeon; CLI defined as persistent ischemic rest pain for greater than or equal to 2 weeks and/or ulceration or gangrene of the toe or foot
- •Estimated life expectancy > 6 months as deemed by patient's clinician and/or investigator
- •Suitable candidate for a bone marrow aspiration, deemed by Consultant Haematologist
- •Chronic critical limb ischaemia with rest pain (Rutherford Class 4) or mild-to-moderate tissue loss (Rutherford Class 5) who are not candidates for revascularisation
- •Medically fit to undergo bone marrow harvest and stem cell intramuscular injection
- •One of the following haemodynamic parameters: ankle systolic pressure < 70 mmHg or ABI <0.9 TBI <0 .6 TcPO2 <60mmHg on room air
排除标准
- •Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
- •Has received prior therapy with MSCs
- •Has had previous amputation of the talus or above
- •Has failed revascularization within 2 weeks before entry to the study
- •Known Aortoiliac disease with > 50% stenosis
- •Contraindication to intramuscular procedure, including active infection in the affected limb, or wet gangrene or exposed bone or tendon in lower limb with CLI, or in the opinion of the attending clinician, is unsuitable for intramuscular procedure
- •Severe co-morbidity limiting 6 month survival of patients
- •Abnormal liver function as defined by AST and ALT > 2.5 fold the ULN and total bilirubin > 1.5 ULN
- •Significant cognitive impairment (Mini Mental Status Examination <22)
- •Presence of proliferative retinopathy (in participants with diabetes mellitus only)
- •Presence of poorly controlled diabetes mellitus with HbAIc > 10% within previous 3 months
- •HIV or HBsAg positive
- •Presence of acute coronary syndrome
- •Patient has known active malignancy
- •Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel
- •Patient taking other investigational drugs at the time of enrolment or within 28 days of enrolment
- •Rutherford class 6 CLI
- •Significant bone marrow dysfunction, based on assessment by Haematologist or an established diagnosis of myelodysplasia, or myeloproliferative disorder etc.
- •Bleeding diathesis, coagulopathy, thrombocytopenia etc.
- •Patients in whom delay incurred by attempts at limb salvage using MSCs will adversely affect prognosis in the opinion of the responsible attending clinician
- •Patients with known allergy to foetal bovine serum or trypsin
研究组 & 干预措施
mid dose cohort
40 million hMSCs
干预措施: 40 million hMSCs (Drug)
high dose cohort
80 million hMSCs .
干预措施: 80 million hMSCs (Drug)
low dose cohort
20 million hMSCs .
干预措施: 20 million hMSCs (Drug)
结局指标
主要结局
The number of Serious Adverse Events that are attributable to the treatment
时间窗: 12 months
The number of Serious Adverse Events that are attributable to the MScs
The severity of Serious Adverse Events that are attributable to the treatment
时间窗: 12 months
The number of Serious Adverse Events that are attributable to the MScs
次要结局
- Amputation free survival(12 months)
- median time to amputation,(12 months)
- Change in Ischemic rest pain(12 months.)
- Change in Transcutaneous Pressure of Oxygen TcPO2(12 months)
- Change in Ankle Brachial Index(12 months)
- Collateral vessel formation(12 months)
- Change in Ulcer size(12 months.)
- Change in Quality of Life(12 months.)
研究者
Professor Tim O Brien
Professor Tim o Brien
National University of Ireland, Galway, Ireland