Foot Ulcer Due to Type 2 Diabetes Mellitus
Conditions
Keywords
semaglutide, randomized clinical trial, diabetic foot ulcer
Brief summary
The aim of this exploratory pilot study is to investigate the effect of semaglutide compared to placebo on healing of foot ulcers in type 2 diabetes patients. It is a randomized double blind, placebo controlled, clinical intervention study of 20 weeks intervention.
Interventions
pen for subcutaneous injections
DRUGPlacebo
pen for subcutaneous injections
Sponsors
Ole Lander Svendsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double blinded IP (semaglutide or placebo)
Intervention model description
clinical randomized, double-blind, placebo controlled intervention trial with semaglutide or placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of type 2 diabetes mellitus for at least 6 months * Age 18-90 years * A foot ulcer below the level of the malleoli. If more than one ulcer, the largest will be selected at screening as the index ulcer. * Wound area after sharp debridement of ≥ 5 mm2, but ≤ 3000 mm2.
Exclusion criteria
* Current use, or recent use (\<3 months), of GLP-1 agonists * Current use of DPP-IV inhibitors * Previous acute pancreatitis * Signs of infection of the index ulcer * Toe blood pressure \< 40 mmHg at the foot with the index ulcer * Current treatment with cytotoxic drugs or with systemically administered glucocorticoids * Hospitalisation for a major cardiovascular event or procedure or revascularization surgery on a leg in the last 3 months, or scheduled major cardiovascular intervention * Contraindication/intolerance to study medication * Pre-existing medical condition judged to preclude safe participation in the study * Abuse of alcohol or drugs, or presence of any condition that in the Investigators opinion may lead to poor adherence to study protocol * Recent use (\< 3 months) of an investigational drug or participation in interventional clinical foot ulcer-healing trial * Known pregnancy, breast feeding or planning pregnancy. * Women of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) without a confirmed menstrual period or with a positive highly sensitive pregnancy test). * Women of childbearing potential not using highly effective birth control methods, such as combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal), progestogen-only hormonal contraception (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, sexual abstinence). * Men, with female partners of childbearing potential, not vasectomised or not using condoms or sexual abstinence AND the female partner not using highly effective birth control, such as combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal), progestogen-only hormonal contraception (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion). * Likely inability to comply with the need for weekly visits because of planned activity * Mental incapacity, unwillingness, not speaking and understanding Danish or language barrier precluding adequate understanding or cooperation * Unable to provide written and signed informed consent. * Use of any drug which in the Investigator's opinion could interfere with the healing of foot ulcers. * Any clinically significant disease or disorder, except for conditions associated to the type 2 diabetes, which in the Investigator's opinion could interfere with the results of the trial * Active cancer or a history of cancer in the 3 years prior to signing the informed consent form (history of basal cell carcinoma is allowed). * Life expectancy of less than 12 months. * Wounds caused primarily by untreated vascular insufficiency, or where patients are primarily eligible for vascular intervention to promote wound healing. * Wounds with an etiology not related to diabetes. * Underlying osteomyelitis of the leg with the wound to be treated. * Patients presenting with the clinical characteristics of cellulitis at the wound site (suppurative inflammation involving particularly the subcutaneous tissue, often mild erythema, tenderness, malaise, chills and fever). * Surgery to lengthen Achilles tendon on the leg with the wound to be treated 3 months prior to signing the informed consent form. * Necrosis, purulence, or sinus tracts that cannot be removed by debridement on foot to be treated.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of clinical healed index foot ulcer at week 20 | 20 weeks | Difference between the groups treated with semalutide and with placeebo in proportion of index ulcers completely healed after 20 weeks of intervention. Assessment of complete ulcer healing by naked eye will be performed by trained study staff: Total closure/healed (total epithelization): Yes or No. Complete ulcer healing is defined (as by FDA) as complete skin re-epithelialization without drainage or dressing requirements, confirmed at two consecutive study visit two weeks apart, and the time encountered as healed is the first of the two visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in ulcer area after 20 weeks of intervention | 20 weeks | Difference between the groups treated with semalutide and with placebo in change in ulcer area after 20 weeks of intervention. The index ulcers will be photographed using a standard camera. The distance from the ulcer will be appriximately 30 cm and a standard setting will be used for each photograph. A reference ruler will be included in the photograph and located beside the ulcer. The ulcer will be photographed 3 times and stored electronically. The ulcer area will be analyzed using ImageJ software v 1.47 (NIH). |
| Change in ulcer area from time of randomization until 8 and 16 weeks of intervention | 8 and 16 weeks | Difference between the groups treated with semalutide and with placebo in index ulcer area. The index ulcers will be photographed using a standard camera. The distance from the ulcer will be approximately 30 cm and a standard setting will be used for each photograph. A reference ruler will be included in the photograph and located beside the ulcer. The ulcer will be photographed 3 times and stored electronically. The ulcer area will be analyzed using ImageJ software v 1.47 (NIH). |
| Change in distal blood pressure from time of randomization until after 20 weeks of intervention | 20 weeks | Difference between the groups treated with semalutide and with placebo |
Countries
Denmark
Contacts
CONTACTOle L Svendsen, MD
CONTACTklaus Kirketerp-Møller, MD
STUDY_CHAIROle L Svendsen, MD
University Hospital Bispebjerg and Frederiksberg
Outcome results
None listed