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A randomized, split-plot, double-blind, placebo-controlled trial. The varicose ulcer is divided into two (side A and B). Half of the wound's surface is treated locally with insulin (Glargine) applied at an approx depth of 3-4 mm. Treatment with insulin is administered for 7 days. Biopsy specimens of the two sides are obtained on days 0 and 7. A thermographic photograph of the wound is taken at days 0 and 7. The number of blood vessels and fibroplasia is evaluated as the main outcome.
A randomized, split-plot, double-blind, placebo-controlled trial. Chronic Varicose Ulcers measuring more than 4 cm in any of its dimensions, and that comply with candidate criteria are included in the present study. A split-mouth model is used.
The ulcer is divided into two (sides A and B). The side in which treatment is applied is randomized. Half of the wound's surface is treated locally with insulin (Glargine) applied at an approx depth of 3-4 mm. Both halves are covered with dressings and compression therapy is applied. Treatment with insulin is administered for 7 days. Biopsy specimens of the two sides are obtained on days 0 and 7. A thermographic photograph of the wound is taken at days 0 and 7, as control of the local temperature of the wound. This is to asses the process of healing and to correlate with our outcome measures. The number of blood vessels will be evaluated as the main outcome. Fibroplasia and thermal asymmetry between wound sides will be evaluated as secondary outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Topical insulin glargine | Experimental | The wound surface is treated locally with glargine insulin injected sub-dermal in a daily matter for 7 days. Allocation is randomized. |
|
| 0.9% saline solution | Placebo Comparator | The wound surface is treated with conventional wound care in a daily matter for 7 days. Allocation is randomized. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Insulin Glargine | Drug | Half of the wound surface is injected daily with topical glargine insulin |
|
| Measure | Description | Time Frame |
|---|---|---|
| Final angiogenesis | Number of blood vessels in a skin biopsy | Day 7 |
| Measure | Description | Time Frame |
|---|---|---|
| Fibroplasia | Percentage of fibrous tissue in a skin biopsy | Day 7 |
| Thermal asymmetry | Difference between the temperature of the wound and the surrounding healthy tissue |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jose L Ramirez-GarciaLuna, MD, PhD | Universidad Autonoma de San Luis Potosí | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mario Aurelio Martínez-Jiménez | San Luis Potosí City | San Luis Potosí | 78220 | Mexico |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29845043 | Result | Martinez-Jimenez MA, Valadez-Castillo FJ, Aguilar-Garcia J, Ramirez-GarciaLuna JL, Gaitan-Gaona FI, Pierdant-Perez M, Valdes-Rodriguez R, Sanchez-Aguilar JM. Effects of Local Use of Insulin on Wound Healing in Non-diabetic Patients. Plast Surg (Oakv). 2018 May;26(2):75-79. doi: 10.1177/2292550317740688. Epub 2017 Nov 22. | |
| 24281606 |
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Anonymized data will be available upon request after the publication of results.
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| ID | Term |
|---|---|
| D014647 | Varicose Ulcer |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D014648 | Varicose Veins |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D007871 | Leg Ulcer |
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| ID | Term |
|---|---|
| D000069036 | Insulin Glargine |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D049528 | Insulin, Long-Acting |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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Parallel assignment Randomized split-plot design
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Double (Participant, Investigator) Double Blind (Participant, Investigator)
| Saline | Drug | Half of the wound surface is injected daily with topical saline solution |
|
| Day 7 |
| Hypoglycaemia | Presence of capillary blood glucose of <60 mg/dl or clinical symptoms of hypoglycemia | Day 7 |
| Martinez-Jimenez MA, Aguilar-Garcia J, Valdes-Rodriguez R, Metlich-Medlich MA, Dietsch LJP, Gaitan-Gaona FI, Kolosovas-Machuca ES, Gonzalez FJ, Sanchez-Aguilar JM. Local use of insulin in wounds of diabetic patients: higher temperature, fibrosis, and angiogenesis. Plast Reconstr Surg. 2013 Dec;132(6):1015e-1019e. doi: 10.1097/PRS.0b013e3182a806f0. |
| 35932720 | Derived | Martinez-Jimenez MA, Kolosovas-Machuca S, Alcocer F, Ortiz-Dosal LC, Gonzalez-Grijalva MC, Delsol-Revuelta GA, Gaitan-Gaona FI, Valadez-Castillo FJ, Ramirez-GarciaLuna JL. A Randomized Controlled Trial on the Effect of Local Insulin Glargine on Venous Ulcer Healing. J Surg Res. 2022 Nov;279:657-665. doi: 10.1016/j.jss.2022.06.070. Epub 2022 Aug 3. |
| D012883 |
| Skin Ulcer |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |