Autologous Stem Cells for the Treatment of No Option Critical Limb Ischemia
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.
研究概览
详细说明
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.
Study Design: Open label, uncontrolled, non-randomized, dose escalation study. Sample Size: 9 Method of Participant Assignment:Sequential administration of 3 escalating doses of autologous bone marrow-derived mesenchymal stem cells.
Examination Points: Day 0, 7, 30, 90, 180, 365 and 730 Primary Outcome: Serious adverse events that are attributable to intervention. Secondary Outcomes :Amputation free survival, median time to amputation, TcPo2, ABI, pain scale, ulcer healing, quality of life assessments, collateral vessel formation detected by MRI at 12 months.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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Galway
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Galway City、Galway、爱尔兰
- Galway University Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
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of any study-related procedure not part of standard medical care, and with the understanding that consent may be withdrawn at any time without prejudice to future medical care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
Exclusion Criteria:
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
- Pregnancy
- 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
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学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:顺序分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:low dose cohort
20 million hMSCs .
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其他名称:
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实验性的:mid dose cohort
40 million hMSCs
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其他名称:
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实验性的:high dose cohort
80 million hMSCs .
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其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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The number of Serious Adverse Events that are attributable to the treatment
大体时间:12 months
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The number of Serious Adverse Events that are attributable to the MScs
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12 months
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The severity of Serious Adverse Events that are attributable to the treatment
大体时间:12 months
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The number of Serious Adverse Events that are attributable to the MScs
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12 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Amputation free survival
大体时间:12 months
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Efficacy measured by the presence or absence of the target limb
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12 months
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median time to amputation,
大体时间:12 months
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Efficacy measured by the duration from time of cell administration to time of amputation if applicable.
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12 months
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Change in Transcutaneous Pressure of Oxygen TcPO2
大体时间:12 months
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Efficacy will be determined by improvement from baseline in mmHg
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12 months
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Change in Ankle Brachial Index
大体时间:12 months
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"Ankle Brachial Index: An indicator of peripheral perfusion measured by dividing Ankle Pressure (mmHg) by brachial pressure (mmHg) (normal ABI is 1.0 ).
Efficacy outcome will be measured by improvement from baseline .
The higher the ABI, the better the outcome."
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12 months
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Collateral vessel formation
大体时间:12 months
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Efficacy will be determined the presence of collateral vessel formation as detected by MRI
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12 months
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Change in Ischemic rest pain
大体时间:12 months.
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Efficacy will be determined by decrease in score from baseline as measured by verbal analogue scale (0 = no pain, 10 = worst pain in life)
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12 months.
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Change in Ulcer size
大体时间:12 months.
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Efficacy will be determined by decrease in the surface area from baseline as measured by ImageJ software and or complete healing of the ulcer
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12 months.
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Change in Quality of Life
大体时间:12 months.
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Efficacy will be measured using the EQ 5D Quality of Life assessment tool
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12 months.
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合作者和调查者
调查人员
- 首席研究员:Timothy O Brien, PhD、NUIG
出版物和有用的链接
一般刊物
- Mohamed SA, Howard L, McInerney V, Hayat A, Krawczyk J, Naughton S, Finnerty A, Holohan M, Duffy A, Moloney T, Kavanagh E, Burke P, Liew A, Tubassam M, Walsh SR, O'Brien T. Autologous bone marrow mesenchymal stromal cell therapy for "no-option" critical limb ischemia is limited by karyotype abnormalities. Cytotherapy. 2020 Jun;22(6):313-321. doi: 10.1016/j.jcyt.2020.02.007. Epub 2020 Apr 6.
- EU Clinical Trials Register Clinical trial results 2013-003447-37 version 1 EU-CTR publication date: of 21 01 January 2021
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
20 million hMSCs的临床试验
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University of Miami暂时不可用中风,缺血性 | 中风,急性 | 间充质干细胞 | 急性缺血性中风 | 中风/脑部发作美国
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University of MiamiNational Heart, Lung, and Blood Institute (NHLBI); The Emmes Company, LLC完全的
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Million Marker Wellness, Inc.完全的
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Joshua M HareNational Heart, Lung, and Blood Institute (NHLBI)完全的
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Ihsan M Salloum, MD, MPHNational Institute on Alcohol Abuse and Alcoholism (NIAAA)招聘中
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Medical College of WisconsinChildren's Hospital and Health System Foundation, Wisconsin招聘中急性淋巴细胞白血病 | 急性淋巴细胞白血病,儿科 | 急性淋巴细胞白血病,复发 | 急性淋巴细胞白血病复发 | 缓解失败的急性淋巴细胞白血病 | 急性淋巴细胞白血病未达到缓解美国
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Medical College of WisconsinChildren's Hospital and Health System Foundation, Wisconsin完全的