Clinical trial NCT04746599: Autologous Fat Grafting in the Treatment of Critical Limb Ischaemia
Official title: Autologous Fat Grafting in the Treatment of Critical Limb Ischaemia Non Suitable for Revascularization: The Adipose Tissue - Critical Limb Ischaemia (ADIPOCLI) Trial Protocol
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Critical Limb Ischemia
Peripheral Arterial Disease - PAD
Ischemic Ulcer
Ischemic Feet
Diabetic Foot
Scleroderma, Systemic
Thrombo Angiitis Obliterans
Ischemic Leg
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
First posted: 2021-02-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Critical Limb Ischaemia (CLI) is a condition characterized by chronic ischemic at-rest pain, ulcers, or gangrene for more than 2 weeks in one or both legs, attributable to objectively proven arterial occlusive disease.CLI is associated with a high risk of lower amputation, diminished quality of life and mortality. Revascularization by either bypass surgery or endovascular recanalization is considered the first-choice treatment in patients with CLI.

Revascularization is not always possible because patients with CLI often have severe comorbidities or because it is not technically feasible.

On the basis of their well-recognized regenerative and angiogenetic properties, cell therapy with autologous bone marrow-derived mesenchymal stem cells (BMMSCs) has been proposed and tested in different animal models and in some human pathological conditions characterized by peripheral ischemia and wound formation.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Age \> 18
* Established diagnosis of CLI according to TransAtlantic InterSociety Consensus (TASC II) guidelines
* Ankle oxygen partial pressure \< 40 mmHg with no ischaemic lesions or \< 60 mmHg with ischaemic lesions
* Tibial injections site free from ulcers
* Absence of comorbidities responsible for life expectancy \< 6 months
* Non suitability for surgery (comorbidities or angiographic results)
* Informed consent taken

Exclusion Criteria:

* Age \< 18 years
* Inability of understanding and signing informed consent
* Tibial injections sites involved by ulcers
* Life expectancy \< 6 months
* Unwillingness to attend follow up
* Any of the following: women who are or may be pregnant or women hoping to become pregnant; women who are breastfeeding; men whose partners hope to become pregnant during the treatment period

Primary outcomes:
measure: Pain reduction
timeFrame: 7 days
Secondary outcomes:
measure: Limb salvage
timeFrame: 30 days
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore di Milano
Study officials:
affiliation: Fondazione IRCCS Cà Granda Ospedale Maggiore
name: Santi Trimarchi, Prof
role: PRINCIPAL_INVESTIGATOR
References: