The goal of this study is to investigate the safety and efficacy of allogenic mesenchymal stem cells isolated from adipose tissue as the treatment for chronic wounds in diabetic foot syndrome in a double-blinded three armed setup.
Patients will be randomized and assigned to one of three study groups, and will receive according IMP solutions: 1) two doses of cell solution; 2) one dose of cell solution and one dose of placebo solution; 3) two doses of placebo solutions. During the study Patients will attend to weekly visits for routine monitoring and SOC treatment. The IMP solutions will be administered in two weeks intervals, on day 0 and day 14 of the treatment, and the control visits are scheduled on days 7, 21, 28, 35 and 42 - for a total of 7 visits during the active phase of the study. The follow-up visits will be performed 8, 26 and 52 weeks after the last visit in the active phase (day 42).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
105
ADSC/ASC will be administered twice, at two-week intervals - during V0 and V2 visits The first dose will be administered one week after the randomisation visit. Control visits after administration will be performed every week, up to V6 visit (up to 6 weeks after V0).
ADSC/ASC will be administered once, at the time of the second application patients will receive a placebo - during V0 and V2 visits The first dose will be administered one week after the randomisation visit. Control visits after administration will be performed weekly, up to V6 visit (up to 6 weeks after V0)
Change in wound size (%) at 6 weeks after first study treatment administration compared to baseline with the actual wound size measured by the independent assessor.
Percentage change in wound size, measured by an independent assessor using a standardized wound area measurement method. The calculation is based on the difference between the baseline wound size and the wound size at 6 weeks, expressed as a percentage of the baseline value.
Time frame: 6 weeks after the first administration
Type, frequency and severity of adverse events (assessed according CTCAE v5.0); change from baseline of laboratory parameters and selected vital signs of the participants.
Adverse events will be assessed based on type, frequency, and severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Changes from baseline in laboratory parameters and selected vital signs will be evaluated using standardized clinical measurement methods.
Time frame: 6 weeks after the first administration
Early efficacy of the allogenic ADSC/ASC defined as percentage of patients with significant clinical success defined as complete wound closure (100% epithelialization), or partial epithelialization of the wound (>50% epithelialization)
The percentage of patients achieving significant clinical success, defined as either complete wound closure (100% epithelialization) or partial epithelialization of the wound (\>50%). Wound epithelialization will be assessed using standardized wound assessment criteria by an independent assessor.
Time frame: 6 weeks after the first administration
Long-term efficacy of the allogenic ADSC/ASC defined as percentage of patients with significant clinical success defined as complete wound closure (100% epithelialization), or partial epithelialization of the wound (>50% epithelialization) over time.
The percentage of patients achieving significant clinical success, defined as either complete wound closure (100% epithelialization) or partial epithelialization of the wound (\>50%), assessed over time. Wound epithelialization will be evaluated using standardized wound assessment criteria by an independent assessor at predefined time points.
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Placebo will be administered twice, at two-week intervals - during V0 and V2 visits The first dose will be administered one week after the randomisation visit. Control visits after administration will be performed every week, up to V6 visit (up to 6 weeks after V0).
Time frame: Through study completion, an average of 1 year
The dynamics of wound healing defined as the time required for patients to reach the wound size reduction thresholds: 50% reduction of the wound; maximum reduction of the wound area (%); complete wound healing .
The time required for patients to achieve predefined wound size reduction thresholds, including 50% wound size reduction, maximum wound area reduction (percentage), and complete wound healing (100% epithelialization). Wound size will be measured using standardized wound assessment methods by an independent assessor at predefined time points.
Time frame: 6 weeks after the first administration and through study completion, an average of 1 year
Absolute change in the wound-associated pain perception over time assessed by the patient using visual analogue scale.
Evaluation of the wound-associated pain, assessed by the patient using visual analogue scale. The minimum value is 0 and means "no pain" and the maximum value is 10 and means "the worst possible pain". The lower value the better outcome.
Time frame: 6 weeks after the first administration and through study completion, an average of 1 year
Additional safety parameters such as wound infection requiring antibiotic treatment expressed as total number of patients, and number of antibiotic therapies per patient.
The total number of patients with wound infections requiring antibiotic treatment and the number of antibiotic therapy courses per patient. Infections will be assessed based on clinical criteria and standard medical guidelines.
Time frame: 6 weeks after the first administration and through study completion, an average of 1 year .
Changes in quality of life parameters assessed by the dedicated QoL questionnaire.
Evaluation of the patient's quality of life, assessed by the dedicated QoL questionnaire. The QoL questionnaire consists of 10 questions. Each question is scored 1 to 5. The minimum score is 10 and it means "the best possible state of health", and the maximum score is 50, which means ,,the worst possible state of health".
Time frame: 6 weeks after the first administration and through study completion, an average of 1 year