Ignite Creation Date:
2024-05-05 @ 5:21 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00434616
Status:
UNKNOWN
Last Update Posted:
2011-04-06
First Post:
2007-02-09
Brief Title:
Autologous Bone Marrow Stem Cell Transplantation for Critical Limb-threatening Ischemia
Sponsor:
Franziskus-Krankenhaus
Organization:
Franziskus-Krankenhaus
Study Overview
Official Title:
Security and Effectiveness of Autologous Bone Marrow Stem Cell Transplantation to Avoid Amputations in Patients With Limb-threatening Ischemia A Multicentric Randomized Placebo-controlled Double-blind Study
Status:
UNKNOWN
Status Verified Date:
2011-04
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BONMOT
Brief Summary:
Critical limb ischemia is a condition where the blood circulation in the limbs in most cases the legs is decreased so that pain and non healing wounds ensue Mostly this is a sequel of arteriosclerosis andor diabetes If surgical and other methods for the improvement of blood supply for the leg have failed or are not possible most of these patients will proceed to amputation of the leg
Bone marrow contains cells which can induce and augment the growth of new small arteries called collateral arteries It has been shown in animals and in some case series that the transplantation of a concentrate of the patients own bone marrow with stem cells into the ischemic limb can improve the blood circulation via the induction of collateral growth However it is not known if this bone-marrow stem cell induced collateral growth is sufficient to avoid otherwise necessary amputations
Therefore we conduct a study to compare the efficiency of concentrated bone marrow cells injected into the critically ischemic limb compared to a placebo procedure where only saline is injected We think that the transplantation of autologous bone marrow will reduce the number of necessary leg amputations reduce pain and induce wound healing In this investigation patients with limb threatening ischemia are randomly allocated either to the bone marrow group or to the placebo group Patients in the bone marrow group will have their bone marrow harvested under sedation and the bone marrow cells are concentrated The cell concentrate will then be injected directly into the muscle of the diseased leg Patients in the placebo group will undergo sedation as well but no bone marrow harvest is done and saline is injected into the ischemic leg The procedure will require about 15-2 hours and the subjects will be admitted to a participating vascular Centre Monthly examinations up to three months after the bone-marrow or placebo procedure are done After the follow-up of three months the rate of death and amputations and the wound healing process are compared between groups Adverse and serious adverse events will be recorded during this time period Diagnostic studies will be obtained to measure blood flow in the treated leg during the follow up period and include skin oxygen measurements pressure recordings in the leg and arteriography Also quality of life pain and wound healing will be assessed
After completion of the three months study participation subjects who have been treated with placebo will be able to receive open-label bone marrow transplantation therapy
Bone marrow contains cells which can induce and augment the growth of new small arteries called collateral arteries It has been shown in animals and in some case series that the transplantation of a concentrate of the patients own bone marrow with stem cells into the ischemic limb can improve the blood circulation via the induction of collateral growth However it is not known if this bone-marrow stem cell induced collateral growth is sufficient to avoid otherwise necessary amputations
Therefore we conduct a study to compare the efficiency of concentrated bone marrow cells injected into the critically ischemic limb compared to a placebo procedure where only saline is injected We think that the transplantation of autologous bone marrow will reduce the number of necessary leg amputations reduce pain and induce wound healing In this investigation patients with limb threatening ischemia are randomly allocated either to the bone marrow group or to the placebo group Patients in the bone marrow group will have their bone marrow harvested under sedation and the bone marrow cells are concentrated The cell concentrate will then be injected directly into the muscle of the diseased leg Patients in the placebo group will undergo sedation as well but no bone marrow harvest is done and saline is injected into the ischemic leg The procedure will require about 15-2 hours and the subjects will be admitted to a participating vascular Centre Monthly examinations up to three months after the bone-marrow or placebo procedure are done After the follow-up of three months the rate of death and amputations and the wound healing process are compared between groups Adverse and serious adverse events will be recorded during this time period Diagnostic studies will be obtained to measure blood flow in the treated leg during the follow up period and include skin oxygen measurements pressure recordings in the leg and arteriography Also quality of life pain and wound healing will be assessed
After completion of the three months study participation subjects who have been treated with placebo will be able to receive open-label bone marrow transplantation therapy
Detailed Description:
Peripheral arterial disease PAD represents very advanced arteriosclerosis It is not unusual for this condition to result in limb-threatening ischemia that usually results in amputation of the limb About 150000 thigh or calf amputations due to PAD are done annually in the United states
Treatment of critical limb threatening ischemia corresponding to Rutherford grade II or III consists of revascularization of the leg with critically reduced blood supply Depending on the localization and morphology of the occlusion surgical revascularization by means of bypass surgery or catheter-based percutaneous transluminal angioplasty PTA may be used even as a complementary procedure However successful revascularization is possible in only max 60 to 70 of the patients affected Patients with limb threatening ischemia which cannot be revascularized have a one-year amputation rate exceeding 80 and a 20-30 mortality
Several studies have shown that in less advanced PAD the implantation of a concentration of mononuclear cells harvested from the patients own bone marrow has been effective in developing collateral vessel formation translating into an improvement in PAD symptoms Additional clinical evidence that this simple safe and inexpensive therapy can induce therapeutic angiogenesis in the ischemic limb sufficient to prevent amputation would be valuable to both patients and clinicians
This study will evaluate the clinical potential for the implantation of a concentration of bone marrow mononuclear cells which contain stem cells for therapeutic angiogenesis through the augmented formation of collateral vessels in the ischemic limb It is a placebo-controlled 11 randomized study with a total of 90 patients included The placebo procedure consists of a sham bone marrow puncture where no bone marrow aspiration is done instead only a stab puncture of the skin is made
The bone marrow cell concentrate will be prepared point of care patient-side from an aspirate of 240 mL of bone marrow A concentrate volume of 40-50 mL will be injected into 40-50 sites in the muscles of the ischemic limb A blinded physician injects either the bone marrow cell concentrate or the visually identical placebo solution into the ischemic leg
Improvement in perfusion of the limb will be measured using clinical assessment and ankle-brachial-index ABI transcutaneous oxygen TcPO2 and contrast angiography Quality of life and pain will be assessed
Study participation ends for the subjects after a follow-up of three months with monthly visits After this clinical and perfusion status are recorded at least three-monthly up to two years after study inclusion
HYPOTHESIS
Implantation of Bone Marrow stem cell Aspirate Concentrate BMAC can be clinically effective in treating critical limb threatening ischemia so that the number of amputations can be reduced
Inclusion criteria
Presence of Critical Limb ischemia according to the guidelines of the Transatlantic Consensus Group TASC Rutherford grade II or III Perfusion is measured with absolute perfusion pressure and ankle-brachial index ABI and transcutaneous oxygen tension TcpO2 for inclusion ABI has to be less than or equal to 06 or absolute ankle pressure must be less than 60 mmHg If ABI is technically not feasible eg in patients with media calcification inclusion criteria are a tcpO2 value supine forefoot 44C of less than 20 mmHg if there is no tissue loss or a tcpO2 of less than 40 mmHg if there is tissue loss
No sufficient response to best standard care delivered for six weeks
No surgical or radiological interventional option for revascularisation as confirmed by a vascular surgeon and an interventional radiologist
Age older than 18 years
Signed informed consent
Absence of life-threatening complications from the ischemic limb
Exclusion criteria
Expected life span less than six months
Bone marrow diseases which preclude transplantation eg lymphoma leukemia myelodysplastic syndrome and others
Renal failure on hemodialysis
Life threatening complications of limb ischemia with the need for immediate limb amputation to avoid death or clinical deterioration
End points
Primary end point Major amputation above the ankle of the index limb after 3 months or persisting critical limb ischemia of the index limb after three months
Secondary end points
Wound healing wound size wound stage
Pain and analgesics use
Rutherford grade and stage
Walking distance treadmill if possible
Quality of life EQ-5D Questionnaire
Transcutaneous oxygen pressure TcpO2 ABI absolute ankle perfusion pressure
Collateral artery number as judged by contrast angiography after 3 months
Rate and extent of minor below the ankle amputations in the index limb
Treatment of critical limb threatening ischemia corresponding to Rutherford grade II or III consists of revascularization of the leg with critically reduced blood supply Depending on the localization and morphology of the occlusion surgical revascularization by means of bypass surgery or catheter-based percutaneous transluminal angioplasty PTA may be used even as a complementary procedure However successful revascularization is possible in only max 60 to 70 of the patients affected Patients with limb threatening ischemia which cannot be revascularized have a one-year amputation rate exceeding 80 and a 20-30 mortality
Several studies have shown that in less advanced PAD the implantation of a concentration of mononuclear cells harvested from the patients own bone marrow has been effective in developing collateral vessel formation translating into an improvement in PAD symptoms Additional clinical evidence that this simple safe and inexpensive therapy can induce therapeutic angiogenesis in the ischemic limb sufficient to prevent amputation would be valuable to both patients and clinicians
This study will evaluate the clinical potential for the implantation of a concentration of bone marrow mononuclear cells which contain stem cells for therapeutic angiogenesis through the augmented formation of collateral vessels in the ischemic limb It is a placebo-controlled 11 randomized study with a total of 90 patients included The placebo procedure consists of a sham bone marrow puncture where no bone marrow aspiration is done instead only a stab puncture of the skin is made
The bone marrow cell concentrate will be prepared point of care patient-side from an aspirate of 240 mL of bone marrow A concentrate volume of 40-50 mL will be injected into 40-50 sites in the muscles of the ischemic limb A blinded physician injects either the bone marrow cell concentrate or the visually identical placebo solution into the ischemic leg
Improvement in perfusion of the limb will be measured using clinical assessment and ankle-brachial-index ABI transcutaneous oxygen TcPO2 and contrast angiography Quality of life and pain will be assessed
Study participation ends for the subjects after a follow-up of three months with monthly visits After this clinical and perfusion status are recorded at least three-monthly up to two years after study inclusion
HYPOTHESIS
Implantation of Bone Marrow stem cell Aspirate Concentrate BMAC can be clinically effective in treating critical limb threatening ischemia so that the number of amputations can be reduced
Inclusion criteria
Presence of Critical Limb ischemia according to the guidelines of the Transatlantic Consensus Group TASC Rutherford grade II or III Perfusion is measured with absolute perfusion pressure and ankle-brachial index ABI and transcutaneous oxygen tension TcpO2 for inclusion ABI has to be less than or equal to 06 or absolute ankle pressure must be less than 60 mmHg If ABI is technically not feasible eg in patients with media calcification inclusion criteria are a tcpO2 value supine forefoot 44C of less than 20 mmHg if there is no tissue loss or a tcpO2 of less than 40 mmHg if there is tissue loss
No sufficient response to best standard care delivered for six weeks
No surgical or radiological interventional option for revascularisation as confirmed by a vascular surgeon and an interventional radiologist
Age older than 18 years
Signed informed consent
Absence of life-threatening complications from the ischemic limb
Exclusion criteria
Expected life span less than six months
Bone marrow diseases which preclude transplantation eg lymphoma leukemia myelodysplastic syndrome and others
Renal failure on hemodialysis
Life threatening complications of limb ischemia with the need for immediate limb amputation to avoid death or clinical deterioration
End points
Primary end point Major amputation above the ankle of the index limb after 3 months or persisting critical limb ischemia of the index limb after three months
Secondary end points
Wound healing wound size wound stage
Pain and analgesics use
Rutherford grade and stage
Walking distance treadmill if possible
Quality of life EQ-5D Questionnaire
Transcutaneous oxygen pressure TcpO2 ABI absolute ankle perfusion pressure
Collateral artery number as judged by contrast angiography after 3 months
Rate and extent of minor below the ankle amputations in the index limb
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| FKH 200 | None | None | None |