Clinical trial NCT01480414: Side Effects of 4 Times Bone Marrow Mono Nuclear Transplantation in Patients With Ischemic Lower Limb
Official title: Evaluation the Side Effects of Repeated Bone Marrow Derived Mono Nuclear Stem Cells Transplantation in Patients With Lower Limb Ischemic Ulcer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ischemic Ulcer
Keywords: bone marrow mono nuclear stem cell ischemic ulcer
Lead sponsor: Royan Institute
Sponsor class: OTHER_GOV
First posted: 2011-11-28
Enrollment: 20
Sex: ALL
Minimum age (years): 20
Maximum age (years): 62
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Critical limb ischemia (CLI) results from severe occlusive disease that impairs distal limb perfusion to the point where oxygen delivery is no longer adequate to meet the metabolic needs of the tissue, even under resting conditions. The limits of peripheral artery disease (PAD) compensatory mechanisms, such as distal vasodilatation and collateral formation, have been exceeded at this point. PAD is a widespread disease, affecting up to 15% of all adults older than 55 years. Formation of true new blood vessels, or angiogenesis, and development of collateral vessels from preexisting blood vessels, or arteriogenesis, is important in the pathophysiology of vascular disease. By stimulating these processes the investigators might be able to provide an alternative treatment strategy for patients with lower limb ischemia. In response to tissue injury and remodeling, neovascularization usually occurs via the proliferation and migration of progenitor endothelial cells (EPC) from preexisting vasculature. Indeed, recent studies have shown that bone-marrow mononuclear cell (BM-MNC) implantation increases collateral vessel formation in patients with limb ischemia. So the investigators determine to evaluate the efficacy of repeated MNC transplantation in patients with ischemic lower limb.

Detailed description: In this study we transparent bone marrow derived mononuclear stem cells 4 times to the ischemic limb of 11 patients with PAD.first of all all the patients evaluate by physical examination,PFWD,ABI and serologic tests.then underwent bone marrow aspiration to take sample.In our lab the MNC are separated and divided in to equal doses.one of them inject to the ischemic foot and the othr one are freezed and inject after 3weeks.3 weeks after second injection again patient underwent bone marrow aspiration and the same process repeat.then after 4times transplantation,patients are followed up after 1,3,6,9,12 months after injection and evaluate by physical examination,PFWD,ABI and serologic tests.all the data are collected and analysed and the result will be shown.3 patients underwent cell transplantation just one time due to one time bone marrow aspiration.They are followed up after 1,3,6,9,12 months after injection and evaluate by physical examination,PFWD,ABI and serologic tests.at the end of the study patients with 4imes injection and 1time injection will be compared.

Eligibility criteria: Inclusion Criteria:

* Ischemic lower limb based on TASK guide line
* Rutherford score:2,3
* ABI\<0.6
* Absolute ankle pressure \< 60 mmHg
* Both gender
* Age:20-62years

Exclusion Criteria:

* EF\<30%
* Cr\>2
* HbA1c\>8%
* Bone marrow disorders:leukemia
* Cognitive disorders
* Infections
* MI with ST elevation during last month
* Malignancy
* Immunologic or rheumatologic disorders

Primary outcomes:
measure: side effects
timeFrame: 3months
Secondary outcomes:
measure: PFWD
timeFrame: 3months
measure: ABI
timeFrame: 3months
measure: size and depth of ulcer
timeFrame: 3months
measure: Amputation
timeFrame: 6months
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Royan Institute
Study officials:
affiliation: Head of Royan Institute
name: Hamid Gourabi, PhD
role: STUDY_CHAIR
affiliation: surgery scientist
name: mohammad zafarghandi, MD
role: STUDY_DIRECTOR
affiliation: head of Royan cell therapy center
name: Nasser Aghdami, MD,PhD
role: STUDY_DIRECTOR
affiliation: Surgery scientist
name: Behnam Molavi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Molavi B, Zafarghandi MR, Aminizadeh E, Hosseini SE, Mirzayi H, Arab L, Baharvand H, Aghdami N. Safety and Efficacy of Repeated Bone Marrow Mononuclear Cell Therapy in Patients with Critical Limb Ischemia in a Pilot Randomized Controlled Trial. Arch Iran Med. 2016 Jun;19(6):388-96.