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| ID | Type | Description | Link |
|---|---|---|---|
| 050343290-0702201132855389 | Registry Identifier | Clinical Trials Registry - India (CTRI) |
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| Name | Class |
|---|---|
| Thermogenesis Corp. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Autologous Bone Marrow Mononuclear cells (BMMNCs) | Other | Multiple intramuscular injections of concentrated bone marrow derived mononuclear cells (0.5 cc/injection) into the ischemic muscle of the affected limb. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 1, 3, 6 and 12 Months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and 12 month |
| Measurement of Mean Change in Ankle Brachial Index From Baseline to 12 Months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Venkatesh Ponemone, PhD | TotipotentRX, Center for Cellular Medicine | Study Director |
| Kenneth Harris, MS | TotipotentRX, Centre for Cellular Medicine | Study Chair |
| Suhail Bukhari, MBBS, FNBE | Fortis Escorts Heart Institute and Research Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fortis Escorts Heart Institute & Research Centre | New Delhi | New Delhi | India |
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| ID | Title | Description |
|---|---|---|
| FG000 | BMMNC Treated Group | All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells (BMMNCs) concentrate prepared using the Res-Q 60 technology (a point of care system) and injected the concentrate intra-muscularly into multiple sites in the ischemic tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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A total of 17 subjects who met the eligibility criteria were enrolled in this study.
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| ID | Title | Description |
|---|---|---|
| BG000 | BMMNC Treated Group | All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) and injected intra-muscularly into multiple sites in the ischemic muscle of the affected limb at 0.5 cc/injection for a total of 15-20 cc. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Number | participants | 1, 3, 6 and 12 Months |
|
Adverse events were reported for the duration of the study, that is, from baseline to 12 Months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BMMNC Treated Group | All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) and injected intra-muscularly into multiple sites in the ischemic muscle of the affected limb at 0.5 cc/injection for a total of 15-20 cc. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Major Limb Amputation | Vascular disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Venkatesh Ponemone | TotipotentSC | +91-124-4976860 | venkatesh.ponemone@totipotentsc.com |
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| ID | Term |
|---|---|
| D000089802 | Chronic Limb-Threatening Ischemia |
| D058729 | Peripheral Arterial Disease |
| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
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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. |
| 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. | 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. | 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. | 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. | Baseline, 1, 3, 6 and 12 months |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) and injected intra-muscularly into multiple sites in the ischemic tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc. |
|
|
| Secondary | 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. | Efficacy measures were established by assessing CLI symptoms known to be reliable and valid. The efficacy endpoints were analyzed on per protocol (PP) basis (N=14). | Posted | Mean | Standard Deviation | Number of Vessels | Baseline and 12 month |
|
|
|
| Secondary | 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. | Efficacy measures were established by assessing CLI symptoms known to be reliable and valid. The efficacy endpoints were analyzed on per protocol (PP) basis (N=14). | Posted | Mean | Standard Deviation | Ratio | Baseline, 1, 3, 6 and 12 months |
|
|
|
| Secondary | 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. | The efficacy endpoints were analyzed on per protocol (PP) basis (N=14). | Posted | Mean | Standard Deviation | mmHg | Baseline, 1, 3, 6 and 12 months |
|
|
|
| Secondary | 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. | Efficacy measures were established by assessing CLI symptoms known to be reliable and valid. The efficacy endpoints were analyzed on per protocol (PP) basis (N=14). | Posted | Mean | Standard Deviation | scores on a scale | Baseline, 1, 3, 6 and 12 months |
|
|
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| Secondary | 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. | Efficacy measures were established by assessing CLI symptoms known to be reliable and valid. The efficacy endpoints were analyzed on per protocol (PP) basis (N=14). | Posted | Number | Participants | Baseline, 1, 3, 6 and 12 months |
|
|
|
| Secondary | 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. | Efficacy measures were established by assessing CLI symptoms known to be reliable and valid. The efficacy endpoints were analyzed on per protocol (PP) basis (N=14). | Posted | Number | Participants | Baseline, 1, 3, 6 and 12 months |
|
|
|
| 7 |
| 17 |
| 0 |
| 17 |
| Minor Limb Amputation | Vascular disorders | Systematic Assessment |
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| Death | Cardiac disorders | Systematic Assessment |
|
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| D002318 |
| Cardiovascular Diseases |
| D016491 | Peripheral Vascular Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007511 | Ischemia |
| Title | Measurements |
|---|---|
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| ABI at 6 Months |
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| ABI at 12 Months |
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| Title | Measurements |
|---|---|
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| TcPO2 at 6 Months |
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| TcPO2 at 12 Months |
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| Title | Measurements |
|---|---|
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| Rest Pain Score at 6 Months |
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| Rest Pain Score at 12 Months |
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| Intermittent Claudication Pain Score at Baseline |
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| Intermittent Claudication Pain Score at 1 Month |
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| Intermittent Claudication Pain Score at 3 Months |
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| Intermittent Claudication Pain Score at 6 Months |
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| Intermittent Claudication Pain Score at 12 Months |
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| Title | Measurements |
|---|---|
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| Ulcer and/or Gangrene present at 6 Months |
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| Ulcer and/ or Gangrene present at 12 Months |
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| Title | Measurements |
|---|---|
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| Subjects able to walk at 6 Months |
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| Subjects able to walk at 12 Months |
|