Diabetic Foot Ulcer
Conditions
Keywords
adipose-derived mesenchymal stem cells, chronic wounds, diabetes, foot ulcer
Brief summary
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.
Detailed description
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).
Interventions
BIOLOGICALA - Allogenic ADSC cells in fibrin solution - two times administration ADSC/ASC
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).
BIOLOGICALB - Allogenic ADSC cells in fibrin solution - one time administration of ADSC/ASC, one time of placebo
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)
OTHERC - Standard care in diabetic foot ulcer with aplication of fibrin gel to cover wound surface.
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).
Sponsors
Medical Research Agency, Poland
Medical University of Warsaw
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Patients will be allocated to one of the following arms: Double administration of ADSC/ASC, single administration of ADSC/ASC or Placebo (control) all in addition to SOC treatment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>18 years at the time of consent, 2. The patient's psychophysical and legal ability to give informed consent to participate in the study, 3. Signing the informed consent document for participation in the study, 4. Ulcer classified as diabetic foot syndrome (DFS) of neuropathic and/or neuroischemic etiology corresponding to grade IA/IIA and IC/IIC according to the University of Texas classification (Appendix E), 5. Duration of the ulcer not less than 6 weeks, 6. Presence of a wound with an area of 1-25 cm² (after wound debridement), 7. Satisfactory blood supply to the wound area: * assessed using transcutaneous oxygen pressure measurement, if its value is not less than 30 mmHg, * or measurement of systolic blood pressure at the posterior tibial artery and/or dorsalis pedis artery, which is not less than 50 mmHg, to exclude patients who require revascularization therapy, 8. Glycated hemoglobin (HbA1c) \< 11%, 9. General health status of the patient, which in the investigator's opinion allows participation in all study procedures, 10. Use of the wound offloading method recommended by the investigator, 11. Use of effective contraception methods to avoid pregnancy (see also Appendix F) and/or based on the following criteria: * a woman who is unable to have children (after a hysterectomy or bilateral oophorectomy or post-menopause, defined as a period of at least 12 months since the last menstrual period) is exempt from pregnancy tests, * a woman able to have children with a negative pregnancy test result before the administration of the investigational product on the first day and who agrees to periodic pregnancy testing according to the study protocol and to use highly effective contraceptive methods for one month after the end of the active phase of the study (from V6), or two months after the last administration of the investigational drug (from V2).
Exclusion criteria
1. Etiology of the ulcer other than diabetic foot syndrome, 2. Presence of an active infection in the wound at the time of inclusion in the study, 3. Wound area \<1 cm² or \>25 cm², 4. The patient was enrolled in another clinical trial within the 4 weeks preceding the qualification for this study. 5. Clinically significant limb ischemia: * assessed using transcutaneous oxygen pressure measurement, if its value is lower than 30 mmHg * or measurement of systolic blood pressure at the posterior tibial artery and/or dorsalis pedis artery, if it is lower than 50 mmHg, 6. Presence of an active phase of Charcot joint, 7. Suspected osteitis and/or osteomyelitis within the study wound, 8. Revascularization procedure on the affected lower limb within 3 months prior to study inclusion or planned revascularization procedure, 9. Chronic kidney disease with GFR \< 20 ml/min, 10. Pregnancy and lactation, 11. Allergy to thrombin, 12. Active venous thrombosis, 13. Systemic diseases in the exacerbation stage (acute or decompensated), including heart, kidney, and liver diseases, 14. Active alcohol disease or addiction to psychoactive substances, 15. Allergies to dressing materials used in the study, 16. Oral/intravenous antibiotic therapy at the time of inclusion in the study, 17. Patient undergoing immunosuppressive therapy, including corticosteroid therapy (within 30 days prior to study inclusion), 18. Active cancer or cancer disease in the last 5 years, excluding locally malignant cancers not involving foot tissues, 19. Presence of known clinically active, uncontrolled infections such as hepatitis B, hepatitis C, HIV, and venereal disease (syphilis), 20. Significant features of malnutrition additionally impairing the healing process, regardless of the cause (albumin \< 2.5 g/dl and total protein \< 5 g/dl), 21. Hemoglobin levels \< 9 g/dl, 22. Serum transaminase (alanine and aspartate) activity higher 3x the upper limit of normal (locally).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 6 weeks after the first administration | 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. |
| 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. | 6 weeks after the first administration | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Through study completion, an average of 1 year | 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. |
| 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 . | 6 weeks after the first administration and through study completion, an average of 1 year | 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. |
| Additional safety parameters such as wound infection requiring antibiotic treatment expressed as total number of patients, and number of antibiotic therapies per patient. | 6 weeks after the first administration and through study completion, an average of 1 year . | 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. |
| Changes in quality of life parameters assessed by the dedicated QoL questionnaire. | 6 weeks after the first administration and through study completion, an average of 1 year | 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. |
| Absolute change in the wound-associated pain perception over time assessed by the patient using visual analogue scale. | 6 weeks after the first administration and through study completion, an average of 1 year | 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. |
| 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) | 6 weeks after the first administration | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the additional safety and efficacy parameters such as the percentage of patients requiring lower or upper limb amputation or the percentage of patients experiencing CVD events (CVD death, hospitalization for CVD reason) | through study completion, an average of 1 year | The percentage of patients requiring lower or upper limb amputation and the percentage of patients experiencing cardiovascular events (CVD death, hospitalization for CVD reasons). Events will be assessed based on clinical diagnosis and medical records. |
Contacts
Primary ContactBeata Mrozikiewicz-Rakowska, Assoc.Prof.
Outcome results
None listed