The ADIPOCLI trial is an interventional monocentric trial in which the investigators will evaluate the safety, feasibility and potential efficacy of local administration of autologous adipose derived stromal/stem (ASCs) cell as treatment for pain and ulcers caused by CLI. If the results confirm safety, feasibility and show potential beneficial effects of the intervention regarding clinical parameters, a larger clinical research with longer follow up will be initiated focusing on efficacy. The objective of this clinical trial is to assess the efficacy and safety of ASCs inoculation in peri-tibial area, though reducing pain significantly in patients with CLI not eligible for revascularization.
Autologous fat grafting is widely used for soft-tissue augmentation and replacement in reconstructive and aesthetic surgery providing a biocompatible, natural and inexpensive method. Noteworthy, recent reports have identified adipose tissue as the tissue in the body that contains the highest percentage of adult stem cells. These adipose derived stem cells (ADSCs) can undergo multilineage differentiation and may be crucial for the surgery purpose of healing ulcers as they have potent regenerative effects on endothelium and immunomodulatory properties.
Adipose-derived stromal/stem cells (ASCs) are considered to be an attractive alternative to pluripotent cells with characteristics similar to BMMSCs. Compared with these latter cells, ASCs offer several advantages, including ease of isolation, less donor morbidity, relative abundance, and rapidity of expansion. Preliminary attempts with ASC cell therapy have been made to induce healing of ulcers developed in peripheral vascular diseases of some animal models and human disorders.
The benefits of peritibial inoculation of autologous adipose tissue are the reduction of ischemic pain, the improvement of skin and muscle perfusion, the suspension of major amputation interventions and the healing of trophic lesions if present.
The result of the intervention varies from individual to individual and depends on the engraftment of the transplanted material. In some cases the pain completely disappears. In others, the transplanted material may undergo varying degrees of reabsorption (from 50% to 70%) and therefore a new transplant may be necessary after some time (6-12 months).
The risks are linked to local complications of the procedure such as edema, ecchymosis, pain in the district of surgical aggression (the extent of these three manifestations varies from patient to patient, but are generally modest), dehiscence, bleeding of the wound, site infection surgical.
The study has a total duration of 24 months. The recruitment phase lasts 18 months. After the surgical procedure, the patient will be followed for 6 months, during which he will undergo outpatient visits at 7 and 21 days; then at 1, 3, and 6 months. At each visit, the patient will be assessed for the amount of pain and the transcutaneous oximetry value. As in the usual clinical practice and in the diagnostic-therapeutic path of the arteriopathic patient, instrumental examinations (measurement of the ankle-brachial pressure index - ABI, arterial ultrasound Doppler lower limbs) are performed at the enrollment, at the twenty-first day and 6 months after the procedure .
The investigators will include 20 patients with CLI who satisfy the inclusion criteria. Inclusion and exclusion criteria were designed to select patients with CLI, not suitable for revascularization and who are in reasonable health condition to allow trial participation. Study participants are recruited from our own outpatient population or emergency room. Baseline characteristics are collected during the first visit and include medical examination, ABI and TcPO2 evaluation and Doppler ultrasonography to study the arterial axis of the limb. If CLI is diagnosed, the patient is hospitalized and undergoes an angiography study. Quality of Lyfe test is administered at hospitalization and at follow up.
After angiogram, treatment of choice will be selected during the multidisciplinary vascular conference taking the individual condition of patients into account. Patients eligible for revascularization are submitted to open/endovascular surgery. Patient with CLI unsuitable for revascularization continue hospitalization being given best medical therapy, i.e. pain-killer drugs and prostanoids. Only to these class of patients an adjunctive treatment with local fat grafting is proposed. Information sheet is given to every patient after interview with investigators and informed consent is taken before the procedure.
