Autologous Stem Cells for the Treatment of No Option Critical Limb Ischemia

• Register: ClinicalTrials.gov
• Last refreshed on: 16 March 2021
• Main ID: NCT03455335
• Date of registration: 16/02/2018
• Prospective Registration: No
• Primary sponsor: National University of Ireland, Galway, Ireland
• Public title: Autologous Stem Cells for the Treatment of No Option Critical Limb Ischemia
• Scientific title: 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.
• Date of first enrolment: March 23, 2015
• Target sample size: 12
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03455335
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Ireland

Contacts

• Name: Timothy O Brien, PhD
• Affiliation: NUIG

Key inclusion & exclusion criteria

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may be withdrawn at any time without prejudice to future medical care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 exclusion criteria are not to be enrolled in the
study:

1. Has received prior therapy with MSCs

2. Has had previous amputation of the talus or above

3. Has failed revascularization within 2 weeks before entry to the study

4. Known Aortoiliac disease with > 50% stenosis

5. 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

6. Severe co-morbidity limiting 6 month survival of patients

7. Abnormal liver function as defined by AST and ALT > 2.5 fold the ULN and total
bilirubin > 1.5 ULN

8. Significant cognitive impairment (Mini Mental Status Examination <22)

9. Presence of proliferative retinopathy (in participants with diabetes mellitus only)

10. Presence of poorly controlled diabetes mellitus with HbAIc > 10% within previous 3
months

11. HIV or HBsAg positive

12. Presence of acute coronary syndrome

13. Patient has known active malignancy

14. Pregnancy

15. Likely inability to comply with the protocol or cooperate fully with the investigator
and site personnel

16. Patient taking other investigational drugs at the time of enrolment or within 28 days
of enrolment

17. Rutherford class 6 CLI

18. Significant bone marrow dysfunction, based on assessment by Haematologist or an
established diagnosis of myelodysplasia, or myeloproliferative disorder etc.

19. Bleeding diathesis, coagulopathy, thrombocytopenia etc.

20. Patients in whom delay incurred by attempts at limb salvage using MSCs will adversely
affect prognosis in the opinion of the responsible attending clinician

21. Patients with known allergy to foetal bovine serum or trypsin

-



Age minimum: 18 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Critical Limb Ischemia

Intervention(s)

Drug: 20 million hMSCs

Drug: 40 million hMSCs

Drug: 80 million hMSCs

Primary Outcome(s)

The number of Serious Adverse Events that are attributable to the treatment [Time Frame: 12 months]

The severity of Serious Adverse Events that are attributable to the treatment [Time Frame: 12 months]

Secondary Outcome(s)

Change in Transcutaneous Pressure of Oxygen TcPO2 [Time Frame: 12 months]

Change in Ischemic rest pain [Time Frame: 12 months.]

Collateral vessel formation [Time Frame: 12 months]

Change in Ankle Brachial Index [Time Frame: 12 months]

Change in Ulcer size [Time Frame: 12 months.]

Change in Quality of Life [Time Frame: 12 months.]

median time to amputation, [Time Frame: 12 months]

Amputation free survival [Time Frame: 12 months]

Secondary ID(s)

2013-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University Hospital of Limerick