Critical Limb Ischemia
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUG20 million hMSCs
DRUG40 million hMSCs
DRUG80 million hMSCs
Sponsors
University Hospital of Limerick
National University of Ireland, Galway, Ireland
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Advanced Therapeutic Medicinal Product ( ATMP) Bone Marrow Derived Mesenchymal Stem Cells
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Each patient must meet all of the following inclusion criteria to be enrolled into the study 1. Men and women between the ages of 18 and 85 2. 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 3. 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 4. Estimated life expectancy \> 6 months as deemed by patient's clinician and/or investigator 5. Suitable candidate for a bone marrow aspiration, deemed by Consultant Haematologist 6. 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 7. Medically fit to undergo bone marrow harvest and stem cell intramuscular injection 8. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The number of Serious Adverse Events that are attributable to the treatment | 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 | 12 months | The number of Serious Adverse Events that are attributable to the MScs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Transcutaneous Pressure of Oxygen TcPO2 | 12 months | Efficacy will be determined by improvement from baseline in mmHg |
| Change in Ankle Brachial Index | 12 months | 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. |
| Collateral vessel formation | 12 months | Efficacy will be determined the presence of collateral vessel formation as detected by MRI |
| Amputation free survival | 12 months | Efficacy measured by the presence or absence of the target limb |
| Change in Ulcer size | 12 months. | Efficacy will be determined by decrease in the surface area from baseline as measured by ImageJ software and or complete healing of the ulcer |
| Change in Quality of Life | 12 months. | Efficacy will be measured using the EQ 5D Quality of Life assessment tool |
| Change in Ischemic rest pain | 12 months. | Efficacy will be determined by decrease in score from baseline as measured by verbal analogue scale (0 = no pain, 10 = worst pain in life) |
| median time to amputation, | 12 months | Efficacy measured by the duration from time of cell administration to time of amputation if applicable. |
Countries
Ireland
Outcome results
None listed