Clinical trial NCT05072353: Effectiveness of the Autologous Adipose Tissue Harvested With SEFFICARE Method for Treatment of DFU Minor Amputation
Official title: Autologous Adipose Tissue Harvested With Superficial Enhanced Fluid Fat Injection (SEFFICARE) Method for Treatment of Diabetic Foot Ulcer Undergoing Minor Amputation (SEFFIDiFA): Proposal of Basic Research and Prospective Observational Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetic Foot
Diabetic Foot Ulcer
Amputation
Lead sponsor: Azienda Ospedaliero-Universitaria di Modena
Sponsor class: OTHER
Collaborators: name: University of Modena and Reggio Emilia
First posted: 2021-10-08
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective cohort study
Primary purpose: TREATMENT

Brief summary: Diabetic foot ulcers (DFU) are one of the complications of diabetes mellitus resulting from multiple causes such as neuropathy, ischemia, and infection that contribute to morbidity and amputation. The prevalence of DFU has been estimated to be 3 to 5 times higher than the overall population. Minor amputations (digital or transmetatarsal) are the treatment of choice in case of irreversible DFU. However, many minor amputations do not heal and require re-amputation. Improvements of healing rate after adipose stem cells (ASCs) injection through micro-fragmented autologous adipose tissue of the amputation stump following minor DFU amputation were demonstrated. The use of ASCs obtained from the superficial enhanced fluid fat injection technique (SEFFICARE) to improve the healing process after DFUs minor amputation is the object of the present study.

A single-center non-randomized prospective observational study will be performed.

The recruited patients will undergo local injection of superficial enhanced fluid fat after a lower limb minor amputation. Laboratory analysis to evaluate the composition of the tissue and stromal cell components harvested from adipose tissue with SEFFICARE system by using digital droplets PCR. These data will serve for making associations between the clinical outcome and characteristics of the cell population administered to each patient.

Detailed description: Diabetic foot ulcers (DFU) are one of the complications of diabetes mellitus resulting from multiple causes such as neuropathy, ischemia, and infection that contribute to morbidity and amputation. The prevalence of DFU has been estimated to be 3 to 5 times higher than the overall population. Minor amputations (digital or transmetatarsal) are the treatment of choice in case of irreversible DFU. However, many minor amputations do not heal and require re-amputation. Improvements of healing rate after adipose stem cells (ASCs) injection through micro-fragmented autologous adipose tissue of the amputation stump following minor DFU amputation were demonstrated. The use of ASCs obtained from the superficial enhanced fluid fat injection technique (SEFFICARE) to improve the healing process after DFUs minor amputation is the object of the present study.

STUDY DESIGN: Single-center non-randomized prospective observational cohort study.

TREATMENT: Local injection of superficial enhanced fluid fat after a lower limb minor amputation. Laboratory analysis to evaluate the composition of the tissue and stromal cell components harvested from adipose tissue with SEFFICARE system by using digital droplets PCR. These data will serve for making associations between the clinical outcome and characteristics of the cell population administered to each patient.

INCLUSION CRITERIA:

* type-1 and type-2 diabetes mellitus
* age \>18-years
* both sexes
* chronic diabetic distal ulcers/gangrene (digital or forefoot) intended as W-grade 1 to 3 according to WifI classification;
* absence of active vascular issues or patients undergoing lower extremity revascularization to improve peripheral perfusion intended as I-grade 0 to 2 according to WIfi classification;
* absence of infection signs or presence of soft tissue infection intended as fI-grade 0 to 2 according to Wifi classification, without radiologic signs of bone infection (negative X-ray for osteolytic lesions); SAMPLE SIZE: The correct sample size was calculated considering as primary endpoint the proportion of the healing stump. The sample size was calculated with the Score Z test comparing one proportion based on literature results to a reference value. Using a significance level of 0.05, power of 0.8, setting the H0 proportion of 0.80 and the Ha of 0.6 respectively, the result was 36 subjects. An additional 10% of subjects was considered taking into account eventual drop-out during the study. The final sample size inflated to 40 patients.

ENDPOINTS: Primary endpoint: percentage of stump healing; Secondary endpoints:

* mean time for complete healing;
* evaluation of risk factors afflicting healing/failure;
* evaluation of reintervention (time elapsed since index operation, type, and indication);
* the prevalence of peripheral diabetic polyneuropathy at baseline;
* the percentage change in the pain score of NRS;
* health-related quality of life evaluation, intended as changing of the SF-36 score;
* collection of eventual adverse events related to the treatment procedure and eventual posthoc analysis.
* evaluation of the adipose harvested tissue composition and stromal cell components STATISTICAL ANALYSIS: The categorical endpoints, i.e., the difference in the healing rate will be assessed with the chi-square test or Fisher's exact test. The continuous variables will be calculated by Kaplan-Meier curves and log-rank test. A univariate and multivariate logistic regression analysis will be applied to identify influencing factors on the categorical endpoints. To test the influence of multiple variables on continuous data, one/two-way ANOVA will be performed with Bonferroni's post-test.

Eligibility criteria: Inclusion Criteria:

* type-1 and type-2 diabetes mellitus
* age \>18-years
* both sexes
* chronic diabetic distal ulcers/gangrene (digital or forefoot) intended as W-grade 1 to 3 according to WifI classification;
* absence of active vascular issues or patients undergoing lower extremity revascularization to improve peripheral perfusion intended as I-grade 0 to 2 according to WIfi classification;
* absence of infection signs or presence of soft tissue infection intended as fI-grade 0 to 2 according to Wifi classification, without radiologic signs of bone infection (negative X-ray for osteolytic lesions);

Exclusion Criteria:

* extensive ulcers with deep involving proximal forefoot and/or deep, full-thickness heel ulcer, with calcaneal involvement (W-grade 3 according to WifI classification);
* active vascular issues \[I-grade 3 according to Wifi classification\];
* ulcers with signs of moderate and/or severe infection (osteomyelitis and/or sepsis) \[fI-grade 3 according to WifI classification\];
* severe comorbidities such as severe heart failure, liver failure, and/or psychiatric disorder;
* previous oncological treatments (past 5 years) or ongoing and/or neoplastic lesions;
* corticosteroid therapy;
* coagulopathy;
* infection of the harvesting site;
* local anesthetic allergy;
* immunosuppressive therapy.

Primary outcomes:
measure: Healing
timeFrame: 6 months
Secondary outcomes:
measure: healing time change
timeFrame: 1, 2, 3, 4, 5, 6 months
measure: risk factors afflicting healing/failure
timeFrame: 0 month
measure: reintervention
timeFrame: 6 months
measure: diabetic peripheral neuropathy
timeFrame: 0 month
measure: health-related quality of life change
timeFrame: 1, 2, 3, 4, 5, 6 months
measure: adverse events related to the treatment procedure
timeFrame: 6 months
measure: amount of adipose stem cells used for grafting
timeFrame: 1 month
Other outcomes:
Locations:
city: Modena
country: Italy
facility: Ospedale Civile di Baggiovara (Modena), Azienda Ospedaliero-Universitaria di Modena, Università di Modena e Reggio Emilia
state: Emilia-Romagna
Study officials:
affiliation: University of Modena and Reggio Emilia
name: Roberto Silingardi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Modena and Reggio Emilia
name: Manuela Simoni, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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