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Critical Limb IschemiaPhase 1NCT03455335

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

A Phase 1 study testing 20 million hMSCs, 40 million hMSCs and 80 million hMSCs in people with Critical Limb Ischemia, run by National University of Ireland, Galway, Ireland at 1 site in Ireland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Critical Limb Ischemia
What is being tested?
20 million hMSCs, 40 million hMSCs and 80 million hMSCs
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteIreland
Study dates
23 Mar 2015to 31 Oct 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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of any study-related procedure not part of standard medical care, and with the understanding that consent may be withdrawn at any time without prejudice to future medical care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
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  • 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

Who cannot join

  • 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
Show all 23Show fewer
  • 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
  • -

Trial locations and contacts

1 site in 1 country.

Ireland1 site

  • Galway University Hospital

    Galway, Galway, 0

Other trials in Ireland

About this study

Official 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.

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.

Read the 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.

Being tested
20 million hMSCs, 40 million hMSCs, 80 million hMSCs
Medical subject headings
Chronic Limb-Threatening Ischemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 20 million hMSCsDrug

    Also called 20 million hMSCs intramuscularly

  • 40 million hMSCsDrug

    Also called 40 million hMSCs intramuscularly

  • 80 million hMSCsDrug

    Also called 80 million hMSCs intramuscularly

Study groups in NCT03455335
Study groupRoleWhat they receive
low dose cohortExperimental20 million hMSCs .
Receives: Drug: 20 million hMSCs
mid dose cohortExperimental40 million hMSCs
Receives: Drug: 40 million hMSCs
high dose cohortExperimental80 million hMSCs .
Receives: Drug: 80 million hMSCs

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The number of Serious Adverse Events that are attributable to the treatment

    The number of Serious Adverse Events that are attributable to the MScs

    Measured: 12 months

  2. The severity of Serious Adverse Events that are attributable to the treatment

    The number of Serious Adverse Events that are attributable to the MScs

    Measured: 12 months

Secondary outcomes (8)

  1. Amputation free survival

    Efficacy measured by the presence or absence of the target limb

    Measured: 12 months

  2. median time to amputation,

    Efficacy measured by the duration from time of cell administration to time of amputation if applicable.

    Measured: 12 months

  3. Change in Transcutaneous Pressure of Oxygen TcPO2

    Efficacy will be determined by improvement from baseline in mmHg

    Measured: 12 months

  4. Change in Ankle Brachial Index

    "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."

    Measured: 12 months

  5. Collateral vessel formation

    Efficacy will be determined the presence of collateral vessel formation as detected by MRI

    Measured: 12 months

  6. Change in Ischemic rest pain

    Efficacy will be determined by decrease in score from baseline as measured by verbal analogue scale (0 = no pain, 10 = worst pain in life)

    Measured: 12 months.

  7. Change in Ulcer size

    Efficacy will be determined by decrease in the surface area from baseline as measured by ImageJ software and or complete healing of the ulcer

    Measured: 12 months.

  8. Change in Quality of Life

    Efficacy will be measured using the EQ 5D Quality of Life assessment tool

    Measured: 12 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Mar 2018
  2. Study start23 Mar 2015
  3. Primary completion31 Oct 2019
  4. Study completion31 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Advanced Therapeutic Medicinal Product ( ATMP) Bone Marrow Derived Mesenchymal Stem Cells
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03455335
Sponsor's protocol ID
2013-001
Status last verified
Mar 2021
First submitted
16 Feb 2018
Last updated
4 Mar 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32273232

  • EU Clinical Trials Register Clinical trial results 2013-003447-37 version 1 EU-CTR publication date: of 21 01 January 2021

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 20 million hMSCs, 40 million hMSCs and 80 million hMSCs in people with Critical Limb Ischemia, run by National University of Ireland, Galway, Ireland at 1 site in Ireland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The number of Serious Adverse Events that are attributable to the treatment (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03455335, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2021.

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