Clinical trial NCT06326203: Cell Therapy for Lower Limb Ulcers in Patients With Critical Limb Ischemia
Official title: Randomized, Prospective, Controlled, Single-center, Open-label Phase II Clinical Trial Aimed at Evaluating the Safety and Efficacy of Autologous Mesenchymal Stem Cell Therapy for Lower Limb Ulcers in Patients With Critical Limb Ischemia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Peripheral Arterial Disease
Leg Ulcer
Lead sponsor: UPECLIN HC FM Botucatu Unesp
Sponsor class: OTHER
Collaborators: name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
First posted: 2024-03-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Peripheral arterial disease (PAD) can progress to critical limb ischemia (CLI) of the affected lower limb, characterized by pain at rest, ulcerations or gangrene, with a high risk of amputation. In this phase, the best treatment is arterial limb revascularization, but this is not always possible or even effective for promoting pain relief, healing of ulcers or preventing amputations, in addition to the high socioeconomic cost caused by the disease. Recent advances in cell therapy represent a promising supporting alternative for the treatment of PAD in cases where conventional alternatives have run out. Objective: To evaluate the safety and efficacy of cell therapy with expanded autologous mesenchymal stem cells in the treatment of patients with PAD with CLI and chronic arterial ulcers. Methods: An open randomized clinical study will be performed with 2 groups of 20 patients with CLI: in group 1, a fragment of abdominal fat tissue (10g) will be collected to obtain mesenchymal stem cells, which will be expanded and applied using subcutaneous perilesional injection in the affected lower limb, in addition to the application in the form of a personalized curative biological on the wounds. Group 2 will receive conventional treatment with a Hydrogel dressing with essential fatty acids. Periodic clinical evaluations, complementary exams and photographic record will be carried out. The main outcome of effectiveness will be partial or total wound healing. Safety outcomes will be monitored for infections, gangrene, amputations and deaths. Participants will be monitored for 120 days. Major amputation cases will not be included. An independent external evaluator and blind to the groups will evaluate the results. It is an innovative procedure with high impact and financial return for SUS, in view of the high prevalence of the disease and the high socioeconomic impact of the disease when it progresses to limb amputation.


Eligibility criteria: Inclusion Criteria:

* Absence of distal pulses in the leg (anterior tibial and posterior tibial) and presence or absence of popliteal pulse.
* Peripheral Arterial Disease (PAD).
* Having foot or leg ulcer(s) (distal third) with a minimum area of 1cm2 and a maximum of 3 ulcers totaling up to 20cm2 in the lower limb.
* Having previously received conventional dressing treatment for ulcer indicating no improvement over a minimum period of 3 weeks (antibiotic therapy - if necessary - local care such as mechanical, surgical or chemical debridements - if necessary, dressings).
* PAD with IC classified as Fontaine IV and Rutherford 5.
* Having Ankle Brachial Index (ABI) \<0.9 in infragenicular arteries (anterior tibial, posterior tibial, and fibular) or ABI\>1.3 in one or more infragenicular arteries when suffering from chronic DMT2 (disease duration \> 5 years) not subjected to revascularization treatment or subjected to partial revascularization treatment or treatment failure (stenosis or occlusion) in the last 12 months.
* Inability to revascularize the affected limb (do not have visible infragenicular arteries for surgical approach) and or incomplete revascularization of this limb (undergone endovascular and or surgical treatment that was not able to restore infragenicular pulses) and defined by the doctor that the best available treatment from the surgical vascular point of view has already been performed and was not successful in promoting ulcer healing.
* Drug treatment for PAD and for comorbidities.
* Availability to attend medical appointments.

Exclusion criteria:

* Being pregnant or in the puerperium.
* Having a healed ulcer during the screening period.
* Having signs of systemic infection or active infection in the arterial ulcer or infection of surgical prostheses (bypass, pins, screws). They may be eligible again if they have been successfully treated with antibiotics and the infectious focus has been removed.
* Having an ulcer with devitalized tissue (necrosis). They may be eligible again if they have undergone successful surgical debridement or minor amputations (amputation of toes or limited to the forefoot).
* Having neoplasia and/or being in chemotherapy or radiotherapy treatment or in remission for less than 6 months.
* Being on colchicine or immunomodulators.
* Having infectious diseases such as Human Immunodeficiency Virus (HIV), Hepatitis B and C viruses, Human T-cell Lymphotropic Virus (HTLV); due to the risk of contagion during the manipulation of biological material in the laboratory.
* Having undergone amputation at the level of the leg or thigh in the limb intended to be studied.
* Having COVID-19, diagnosed less than 4 weeks ago.

Primary outcomes:
measure: Major Amputation
timeFrame: 120 days
measure: Ulcer Healing
timeFrame: 7, 30, 60, 90 and 120 days
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: São Paulo State University
name: Francisco J de Oliveira Filho, M.D.
role: PRINCIPAL_INVESTIGATOR
References: