Autologous Bone Marrow Stem Cell Transplantation for Critical, Limb-threatening Ischemia

NCT00434616 | Unknown Phase 2

• 2 other identifiers: 2006-001825-24FKH 200
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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 and/or 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 patient's 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 1.5-2 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.

Conditions

Peripheral Vascular Disease; Diabetic Foot; Peripheral Arterial Occlusive Disease; Leg Ulcer; Gangrene; Ischemia

Keywords

angiogenesis; Arterial Occlusive Diseases; Leg Ulcer; Gangrene; Ischemia; PAOD; Amputation; bone marrow

Outcome Measures

Primary Outcomes (1)

• Major amputation of the index limb or persisting, unchanged critical limb ischemia

  3 months

Secondary Outcomes (9)

• Wound healing (wound size, wound stage)

  3 months

• Pain and analgesics use

  3 months

• Rutherford grade and stage

  3 months

• Walking distance (treadmill) if possible

  3 months

• Quality of life (EQ-5D Questionnaire)

  3 months

Study Arms (2)

1

PLACEBO COMPARATOR

saline injections

Biological: saline injection

2

ACTIVE COMPARATOR

autologous bone marrow transplantation into the ischemic leg

Procedure: Autologous bone marrow cell concentrate transplantation

Interventions

Autologous bone marrow cell concentrate transplantation PROCEDURE

bone marrow aspiration (240 ml), processing and reinjection

2

saline injection BIOLOGICAL

saline injections

1

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Expected life span less than six months
• Bone marrow diseases which preclude transplantation (eg lymphoma, leukaemia, 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

Sponsors & Collaborators

• Franziskus-Krankenhaus: lead
• Klinikum Karlsbad-Langensteinbach: collaborator
• Stiftungsklinikum Boppard: collaborator
• Krankenhaus der Barmherzigen Brüder Trier: collaborator

Study Sites (1)

Franziskus Hospital Berlin Vascular Center

Berlin, State of Berlin, D 10787, Germany

Location

Related Publications (7)

• Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T; Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet. 2002 Aug 10;360(9331):427-35. doi: 10.1016/S0140-6736(02)09670-8.

  PMID: 12241713 BACKGROUND

• Durdu S, Akar AR, Arat M, Sancak T, Eren NT, Ozyurda U. Autologous bone-marrow mononuclear cell implantation for patients with Rutherford grade II-III thromboangiitis obliterans. J Vasc Surg. 2006 Oct;44(4):732-9. doi: 10.1016/j.jvs.2006.06.023. Epub 2006 Aug 22.

  PMID: 16926085 BACKGROUND

• Iba O, Matsubara H, Nozawa Y, Fujiyama S, Amano K, Mori Y, Kojima H, Iwasaka T. Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs. Circulation. 2002 Oct 8;106(15):2019-25. doi: 10.1161/01.cir.0000031332.45480.79.

  PMID: 12370229 BACKGROUND

• Nizankowski R, Petriczek T, Skotnicki A, Szczeklik A. The treatment of advanced chronic lower limb ischaemia with marrow stem cell autotransplantation. Kardiol Pol. 2005 Oct;63(4):351-60; discussion 361. English, Polish.

  PMID: 16273471 BACKGROUND

• Hernandez P, Cortina L, Artaza H, Pol N, Lam RM, Dorticos E, Macias C, Hernandez C, del Valle L, Blanco A, Martinez A, Diaz F. Autologous bone-marrow mononuclear cell implantation in patients with severe lower limb ischaemia: a comparison of using blood cell separator and Ficoll density gradient centrifugation. Atherosclerosis. 2007 Oct;194(2):e52-6. doi: 10.1016/j.atherosclerosis.2006.08.025. Epub 2006 Sep 18.

  PMID: 16982058 BACKGROUND

• Lawall H, Bramlage P, Amann B. Stem cell and progenitor cell therapy in peripheral artery disease. A critical appraisal. Thromb Haemost. 2010 Apr;103(4):696-709. doi: 10.1160/TH09-10-0688. Epub 2010 Feb 19.

  PMID: 20174766 BACKGROUND

• Amann B, Luedemann C, Ratei R, Schmidt-Lucke JA. Autologous bone marrow cell transplantation increases leg perfusion and reduces amputations in patients with advanced critical limb ischemia due to peripheral artery disease. Cell Transplant. 2009;18(3):371-80. doi: 10.3727/096368909788534942. Epub 2009 Apr 2.

  PMID: 19500466 BACKGROUND

Related Links

• Home page of Berlin Vascular Center

MeSH Terms

Conditions

Peripheral Vascular Diseases; Diabetic Foot; Peripheral Arterial Occlusive Disease 1; Leg Ulcer; Gangrene; Ischemia; Arterial Occlusive Diseases

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Diabetic Angiopathies; Foot Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies; Necrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Berthold Amann, MD

  Franziskus Hospital, Berlin Vascular Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 9, 2007
• First Posted: February 13, 2007
• Study Start: April 1, 2007
• Primary Completion: April 1, 2011
• Study Completion: July 1, 2011
• Last Updated: April 6, 2011

Record last verified: 2011-04

Locations

DE (1)