Critical Limb IschemiaPhase 1/2NCT01472289

Safety and Efficacy of Autologous Bone Marrow Mononuclear Cells in Patients With Severe Critical Limb Ischemia

A Phase 1/2 study testing Autologous Bone Marrow Mononuclear cells (BMMNCs) in people with Critical Limb Ischemia, run by TotipotentSC Scientific Product Pvt. Ltd. at 1 site in India.

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 purpose of this study is to evaluate the safety and efficacy of the concentrated autologous bone marrow derived stem cells for the treatment of Critical Limb Ischemia patients. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Critical Limb Ischemia
What is being tested?: Autologous Bone Marrow Mononuclear cells (BMMNCs)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 17 participants
Where: 1 siteIndia
Study dates: Feb 2011to Jul 2013
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Atherosclerotic ischemic peripheral vascular disease (PVD) or Thromboangiitis Obliterans with severe Critical Limb Ischemia (Rutherford Category 4 and 5: ischemic pain at rest and minor tissue loss and Fontaine Class 4: Ischemic ulcers or gangrene, whivh may be dry or humid).
A non-surgical candidate for revascularization e.g. prior vascular reconstruction, inability to locate a suitable vein for grafting, diffuse multi- segment disease, or extensive infra-popliteal disease not amenable to a vascular graft.
Major amputation recommended patients due to severe life threatening PAD.
Subjects must be on maximal tolerated medical therapy for peripheral vascular disease including A) Cessation of smoking B) Referral to endocrinologist for control of HgA1c to < 8% mg/dl, C) control of hyperlipidemia with statins or other anti-hyperlipidemic drugs as indicated, D) control of hypertension as indicated E) Antiplatelet therapy with aspirin and / or cilostazol (unless medically contraindicated, e.g. bleeding or allergy).
Ankle Brachial Pressure Index (ABI) ≤ 0.6 or ankle systolic pressure ≤ 60 mm Hg or TcPO2 ≤ 35 mmHg in the foot.
Subjects who are able to understand the requirements of the study, and willing to provide voluntary written informed consent, which abide by the study requirements, and agree to return for required follow-up visits.

Who cannot join

Subjects with CLI suitable for surgical or percutaneous revascularization and Subjects with acute and chronic inflammatory condition.
CLI patient requiring amputation proximal to trans-metatarsal level
Subjects with spreading (wet) gangrene
Subjects with gait disturbance for reasons other than CLI.
Subjects with poorly controlled diabetes mellitus.
Subjects diagnosed with Thromboangiitis Obliterans (Buerger's Disease) who are smokers and are unwilling or unable to quit smoking or the physician feels the smoking cessation is doubtful.

Show all 18Show fewer

Subjects having moderate to severe COPD with GOLD Classification IIb or III.
Uncontrolled congestive heart failure or Subjects with left ventricular ejection fraction < 25% or AHA Stage C or D heart failure or NYHA Class IV CHF
Stroke or myocardial infarction within last 3 months.
Subjects who are contraindicated for CT Angiogram.
Illnesses or conditions that are uncontrolled or whose control, in the opinion of the Principal Investigator, may be jeopardized by participation in this study or by the complications of this therapy.
Documented terminal illness or cancer or any concomitant disease process with a life expectancy of less than 1 year.
Subjects already enrolled in another investigational drug trial or completed within 3 months.
History of severe alcohol or drug abuse within 3 months of screening.
Hb% < 10 gm%; Serum creatinine ≥ 2.0mg%; Serum total bilirubin ≥2.0mg%; HbA1c > 8.0%.
Women of child bearing potential; pregnant and lactating women.
Subjects with a) myocardial infarction within the last 30 days or left ventricular ejection fraction < 35%, B) Subjects with a cerebrovascular accident within the last 6 months.
INR > 1.5 at the time of Bone Marrow harvest.

Trial locations and contacts

1 site in 1 country.

India1 site

Fortis Escorts Heart Institute & Research Centre
New Delhi, New Delhi

Other trials in India

About this study

Official title: To Study and Demonstrate the Safety and Efficacy of RES-Q Prepared Bone Marrow Mononuclear Cells Injected Into Ischemic Tissue of Patients With Non-Reconstructable Critical Limb Ischemia (CLI).

The purpose of this study is to evaluate the safety and efficacy of the concentrated autologous bone marrow derived stem cells for the treatment of Critical Limb Ischemia patients.

Read the detailed description

A total of 15 patients suffering from end stage IV and V Rutherford /CLI in whom all previous therapeutic strategies failed (e.g. surgical revascularization) will be selected and undergo local transplantation of autologous BMMNCs. Conventional treatments include angioplasty and /or bypass to remove blood vessel blockage for restoring blood supply, along with prescribed medicines that aid in ulcer recovery and wound healing and debridement of damaged/infected tissue. Amputation is inevitable in many cases because some blood capillaries cannot be corrected and restenosis of vessels is very common. Cell therapies with mononuclear cells from patients own bone marrow is promising because these stem cells are capable of stimulating and regenerating capillaries and blood vessels (neovascularization).

This is a Phase Ib (feasibility study), prospective, non randomized and open labeled study aimed to find out the safety and efficacy of intramuscular autologous bone marrow mononuclear cells implantation in patients with chronic critical limb ischemia.

The efficacy/safety of this therapy will be assessed by using several endpoints such as (a) prevention of amputation, (b) wound healing and (c) degree of angiogenesis. In order to assess the limb ischemia, the measurements will be performed at pre- and post transplantation at a variety of time intervals. The measurements include: ABI-ankle brachial index, Transcutaneous partial pressure of Oxygen (TcPO2), 6 min walk test, Rest pain and intermittent Claudication assessment, Healing of ulcers/ wounds and angiography of the affected limb.

Conditions: Critical Limb Ischemia
Being tested: Autologous Bone Marrow Mononuclear cells (BMMNCs)
Keywords: CLI, Peripheral arterial disease
Medical subject headings: Chronic Limb-Threatening Ischemia, Peripheral Arterial Disease

What participants receive

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

Autologous Bone Marrow Mononuclear cells (BMMNCs)Other
Also called Autologous bone marrow mononuclear cell concentrate
Multiple intramuscular injections of concentrated bone marrow derived mononuclear cells (0.5 cc/injection) into the ischemic muscle of the affected limb.

Study groups in NCT01472289
Study group	Role	What they receive
BMMNC treated group	Experimental	Autologous bone marrow mononuclear cell concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) to be injected intramuscularly into multiple sites in the ischemic muscle tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc. Receives: Other: Autologous Bone Marrow Mononuclear cells (BMMNCs)

What is being measured

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

Number of Participants With Adverse Events as a Measure of Safety and Major Limb Amputation Free Survival Post BMMNC Administration
The Primary objective of this study was to determine the safety of intramuscular administration of concentrated autologous BMMNCs harvested, and processed using the Res-Q 60 technology (a point-of-care system). Safety measurements included close vigilance for major limb amputation free survival at 1, 3, 6 and 12 months post BMMNCs administration and stringent reporting of AEs and SAEs.
Measured: 1, 3, 6 and 12 Months

Secondary outcomes (6)

Degree of Angiogenesis Measured by the Number of Collateral Blood Vessels Formed at 12 Months
Measurement of blood supply facilitated by the formation of collateral blood vessels assessed by CT angiography after the procedure.
Measured: Baseline and 12 month
Measurement of Mean Change in Ankle Brachial Index From Baseline to 12 Months
ABI was used to provide a measure of blood flow in the lower limbs. It is the ratio of the blood pressure in the lower limbs to the blood pressure in the upper limbs. Compared to the upper limb, lower blood pressure in the lower limb is an indication of blocked arteries (peripheral vascular disease). The ABI was calculated by dividing the systolic blood pressure at the ankle by the systolic blood pressures in the arm. ABI test was performed at baseline, 1 month, 3 months, 6 months, and 12 months.
Measured: Baseline, 1, 3, 6 and 12 months
Measurement of Change in Transcutaneous Oxygen Pressure (TcPO2) From Baseline to 12 Months
TcPO2 was used to assess the partial pressure (tension) of oxygen in the capillaries of tissues of lower limbs. It was measured by applying a special set of electrodes to the skin. These electrodes contain photoelectric sensors capable of detecting the specific wavelengths of radiation emitted by oxygenated versus reduced hemoglobin.
Measured: Baseline, 1, 3, 6 and 12 months
Change in Rest Pain and Intermittent Claudication Assessment From Baseline to 12 Months
Rest pain is a burning sensation felt at rest, usually in the skin of the foot. It is a symptom of critical ischemia due to severe, chronic, and occlusive peripheral arterial disease (PAD). While, Intermittent Claudication is a crampy leg pain that occurs during exercise, especially walking. The pain is due to the insufficient blood flow in the legs (caused by blocked arteries). Intermittent claudication is the most prominent symptom of PAD.
Both Rest Pain assessment and Intermittent Claudication assessment was performed through Visual Analog Scale or Visual Analogue Scale (VAS). VAS is a psychometric (self-report) response scale that ranges from 0 to 10, where a mark of zero indicates no pain and a mark of 10 indicates worst possible pain.
Measured: Baseline, 1, 3, 6 and 12 months
Clinical Evaluation for the Presence of Ulcer and/or Gangrene in the Affected Limb From Baseline to 12 Months
Evaluation of the integument for ulceration, gangrene and other skin changes in the affected limb was performed at baseline and follow-up visits at 1 month, 3 months, 6 months, and 12 months.The ulceration and gangrene in the affected limb of the subjects was evaluated by visual clinical inspection.
Measured: Baseline, 1, 3, 6 and 12 months
Number of Participants Able to Walk From Baseline to 12 Months as Measured by 6-Minute Walk Test
Subjects were analyzed to see if they were able to walk any distance and the distance covered by patients in 6 minutes was measured to assess the functional changes from baseline. The American Thoracic Society has issued guidelines for the 6-minute walk test (6 MWT). The 6 MWT is safe, easy to administer, well tolerated, and reflects activities of daily living.
Measured: Baseline, 1, 3, 6 and 12 months

Timeline

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

Feb 2011Jul 2013

First posted16 Nov 2011 (estimated)
Study startFeb 2011
Primary completionJan 2013
Study completionJul 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Critical Limb IschemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01472289
Sponsor's protocol ID: TPSC/POC/BMSC/CLI/2010/1b
Other IDs: 050343290-0702201132855389
Status last verified: Oct 2015
First submitted: 18 Jul 2011
Last updated: 18 Nov 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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miRNAs in Critical Limb Ischemia (miRNACLI)
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Laser Atherectomy and Sirolimus-eluting Balloon Angioplasty for CLTI
Chronic Limb Threatening Ischemia
Recruiting
Radiotracer-Based Perfusion Imaging of Patients With Peripheral Arterial Disease
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RecruitingObservational study
Vessel Recoil in Specific CLTI Populations
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Not yet recruiting
DCB Outcomes After Non-Compliant Balloon Vessel Preparation With or Without Scoring in Patients With Femoropopliteal Arterial Disease
Femoropopliteal Disease, Drug Coated Balloon

All Critical Limb Ischemia trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: To Study and Demonstrate the Safety and Efficacy of RES-Q Prepared Bone Marrow Mononuclear Cells Injected Into Ischemic Tissue of Patients With Non-Reconstructable Critical Limb Ischemia (CLI).
ClinicalTrials.gov ID: NCT01472289
Acronym / sponsor ID: TPSC/POC/BMSC/CLI/2010/1b
Conditions: Critical Limb Ischemia
Keywords: CLI, Peripheral arterial disease
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: TotipotentSC Scientific Product Pvt. Ltd.Industry (pharma, biotech, devices)
Collaborators: Thermogenesis Corp.
Study start: Feb 2011
Primary completion: Jan 2013 (actual)
Study completion: Jul 2013 (actual)
First posted: 16 Nov 2011 (estimated)
Results: Posted 18 Nov 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to evaluate the safety and efficacy of the concentrated autologous bone marrow derived stem cells for the treatment of Critical Limb Ischemia patients.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
BMMNC treated group	Experimental	Other: Autologous Bone Marrow Mononuclear cells (BMMNCs)Autologous bone marrow mononuclear cell concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) to be injected intramuscularly into multiple sites in the ischemic muscle tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Atherosclerotic ischemic peripheral vascular disease (PVD) or Thromboangiitis Obliterans with severe Critical Limb Ischemia (Rutherford Category 4 and 5: ischemic pain at rest and minor tissue loss and Fontaine Class 4: Ischemic ulcers or gangrene, whivh may be dry or humid).
A non-surgical candidate for revascularization e.g. prior vascular reconstruction, inability to locate a suitable vein for grafting, diffuse multi- segment disease, or extensive infra-popliteal disease not amenable to a vascular graft.
Major amputation recommended patients due to severe life threatening PAD.
Subjects must be on maximal tolerated medical therapy for peripheral vascular disease including A) Cessation of smoking B) Referral to endocrinologist for control of HgA1c to < 8% mg/dl, C) control of hyperlipidemia with statins or other anti-hyperlipidemic drugs as indicated, D) control of hypertension as indicated E) Antiplatelet therapy with aspirin and / or cilostazol (unless medically contraindicated, e.g. bleeding or allergy).
Ankle Brachial Pressure Index (ABI) ≤ 0.6 or ankle systolic pressure ≤ 60 mm Hg or TcPO2 ≤ 35 mmHg in the foot.

Key exclusion criteria (18 listed)

Subjects with CLI suitable for surgical or percutaneous revascularization and Subjects with acute and chronic inflammatory condition.
CLI patient requiring amputation proximal to trans-metatarsal level
Subjects with spreading (wet) gangrene
Subjects with gait disturbance for reasons other than CLI.
Subjects with poorly controlled diabetes mellitus.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Autologous Bone Marrow Mononuclear cells (BMMNCs)Also: Autologous bone marrow mononuclear cell concentrateMultiple intramuscular injections of concentrated bone marrow derived mononuclear cells (0.5 cc/injection) into the ischemic muscle of the affected limb.	Other	BMMNC treated group

Primary outcome

Number of Participants With Adverse Events as a Measure of Safety and Major Limb Amputation Free Survival Post BMMNC Administration
Time frame: 1, 3, 6 and 12 Months
The Primary objective of this study was to determine the safety of intramuscular administration of concentrated autologous BMMNCs harvested, and processed using the Res-Q 60 technology (a point-of-care system). Safety measurements included close vigilance for major limb amputation free survival at 1, 3, 6 and 12 months post BMMNCs administration and stringent reporting of AEs and SAEs.

6 secondary outcomes

Degree of Angiogenesis Measured by the Number of Collateral Blood Vessels Formed at 12 Months
Time frame: Baseline and 12 month
Measurement of Mean Change in Ankle Brachial Index From Baseline to 12 Months
Time frame: Baseline, 1, 3, 6 and 12 months
Measurement of Change in Transcutaneous Oxygen Pressure (TcPO2) From Baseline to 12 Months
Time frame: Baseline, 1, 3, 6 and 12 months
Change in Rest Pain and Intermittent Claudication Assessment From Baseline to 12 Months
Time frame: Baseline, 1, 3, 6 and 12 months
Clinical Evaluation for the Presence of Ulcer and/or Gangrene in the Affected Limb From Baseline to 12 Months
Time frame: Baseline, 1, 3, 6 and 12 months
Number of Participants Able to Walk From Baseline to 12 Months as Measured by 6-Minute Walk Test
Time frame: Baseline, 1, 3, 6 and 12 months

Results and safety

Results posted to the registry on 18 Nov 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
BMMNC Treated Group	17	15

Primary outcome: Number of Participants With Adverse Events as a Measure of Safety and Major Limb Amputation Free Survival Post BMMNC Administration

Time frame: 1, 3, 6 and 12 Months. Number. Unit: participants

Measure	BMMNC Treated Group n = 17
Major Limb Amputation Free Survival Rate	14
Major Amputation	3
Minor Amputation	2
Unrelated Death	2
Total Adverse Events	7

Population analysed: All the safety end points in the study were analyzed on the ITT population. Out of 17 subjects, adverse events were reported for seven subjects. Of the seven subjects, three underwent major amputation, two reported minor amputation, and two died due to cardiac arrest (unrelated death). Furthermore, major limb amputation free survival rate was 14.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were reported for the duration of the study, that is, from baseline to 12 Months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
BMMNC Treated Group	7 of 17 (41.2%)	0 of 17 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Critical Limb Ischemia

RecruitingObservational study
miRNAs in Critical Limb Ischemia (miRNACLI)
Critical Limb Ischemia
Active, not recruitingObservational study
Laser Atherectomy and Sirolimus-eluting Balloon Angioplasty for CLTI
Chronic Limb Threatening Ischemia
Recruiting
Radiotracer-Based Perfusion Imaging of Patients With Peripheral Arterial Disease
Peripheral Artery Disease, Diabetes Mellitus
RecruitingObservational study
Vessel Recoil in Specific CLTI Populations
Chronic Limb Threatening Ischemia
Not yet recruiting
DCB Outcomes After Non-Compliant Balloon Vessel Preparation With or Without Scoring in Patients With Femoropopliteal Arterial Disease
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Venkatesh Ponemone, PhD study director

TotipotentRX, Center for Cellular Medicine

Kenneth Harris, MS study chair

TotipotentRX, Centre for Cellular Medicine

Suhail Bukhari, MBBS, FNBE principal investigator

Fortis Escorts Heart Institute and Research Centre

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Autologous Bone Marrow Mononuclear cells (BMMNCs) in people with Critical Limb Ischemia, run by TotipotentSC Scientific Product Pvt. Ltd. at 1 site in India.

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 6 inclusion and 18 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 18 Nov 2015. 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 India. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Adverse Events as a Measure of Safety and Major Limb Amputation Free Survival Post BMMNC Administration (time frame: 1, 3, 6 and 12 Months). 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 NCT01472289.

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 18 Nov 2015.