Effects of Local Insulin on Varicose Ulcers for Wound Healing

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Effects of Local Insulin on Wound Angiogenesis and Fibroplasia in Varicose Ulcers

Conditions
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Chronic Venous Disease, Varicose Ulcer, Wound Healing, Insulin, Angiogenesis

Intervention / Treatment
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* Drug: Insulin Glargine
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any gender Presence of varicose ulcer in lower extremities with a size greater than 25 cm2 Absence of infection Exclusion Criteria: Presence of diabetes or glycated hemoglobin >6.5% Comorbidities that affect wound healing Malnutrition Active smoking

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel assignment Randomized split-plot design
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topical insulin glargine<br>The wound surface is treated locally with glargine insulin injected sub-dermal in a daily matter for 7 days. Allocation is randomized. | Drug: Insulin Glargine<br>* Half of the wound surface is injected daily with topical glargine insulin<br>|
| Placebo Comparator: 0.9% saline solution<br>The wound surface is treated with conventional wound care in a daily matter for 7 days. Allocation is randomized. | Drug: Saline<br>* Half of the wound surface is injected daily with topical saline solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final angiogenesis | Number of blood vessels in a skin biopsy | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | 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 | Day 7 | 
| Hypoglycaemia | Presence of capillary blood glucose of <60 mg/dl or clinical symptoms of hypoglycemia | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Varicose Ulcer, Wound Healing, Insulin, Angiogenesis