Improvement of Sensibility in the Foot in Diabetic Patients Induced by EMLA-application to the Lower Leg

Study Overview
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Brief Summary
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Sensory input from the foot as well as all other body parts results in activation of sensory cortex. It is well known that the cortical body map is experienced-dependant and can rapidly change in response to changes in activity and sensory input from the periphery [10-12]. Increased activity and sensory input from the hand results in expansion of the cortical hand representation [13-15], while decreased sensory input, for instance by anaesthesia, amputation or nerve injury, results in shrinkage of the cortical hand representation [16-21]. Due to the constant ongoing cortical competition between body parts the adjacent cortical areas expand and take over the silent area, deprived of sensory input. The investigators have recently described striking examples of such rapid cortical re-organisations induced by selective cutaneous anaesthesia of the forearm: application of EMLA cream to the volar aspect of the forearm results in improved sensory functions of the hand [18] linked to expansion of the hand representational area in sensory cortex . In analogy, EMLA application to the lower leg in healthy controls results in improved sensory functions in the sole of the foot linked to expansion of the foot representational area in sensory cortex. To test the hypothesis that EMLA application to the lower leg of diabetic patients will result in improved sensory functions in the sole of the foot as well as expansion of the foot representation in sensory cortex. The investigators hypothesize that repeated applications of EMLA will result in a long lasting sensibility improvement.

Official Title
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Improvement of Sensibility in the Sole of the Foot in Diabetic Patients, Induced by EMLA-application to the Lower Leg - a Double Blind Study

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: EMLA cream
* Drug: EMLA cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (18-75 years) suffering from diabetes with subjective sensory impairment in the sole of the foot. Exclusion Criteria: Patients with painful neuropathy or established ulcer formation in toes or sole of the foot, known hypersensitivity to local anaesthetics, major vascular reconstructions, communication problems due to severe language problems. Patients with pacemakers or magnetic implants or suffering from claustrophobia will not be subjected to fMRI-investigation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EMLA cream<br> | Drug: EMLA cream<br>* The study subjects are treated either by 50 g of a local anesthetic agent containing 2.5% Lidocaine and 2.5% Prilocaine (EMLA®, AstraZeneca - Södertälje, Sweden) or a placebo cream, applied to the lower leg. The cream is applied under occlusive bandage (plastic foam and a tube) for 1.5 hours circumferential to the lower leg 10-12 cm distally of the tibial tuberosity and the malleolus at ankle level. Administration of the treatment cream as well as removal after 1,5 hour and at sensory assessment after 1.5 hour and 24 hours, and interviewing the patient about subjective experience from the treatment are performed by an independent research nurse, not involved in the sensory assessment.<br>Drug: EMLA cream<br>* 50g applied according to description of intervention<br>|
| Placebo Comparator: Placebo cream<br>A placebo cream identical in appearance and consistency to the experimental cream | Drug: EMLA cream<br>* 50g applied according to description of intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Touch thresholds in the sole of the foot (Semmes-Weinstein monofilaments) |  | Screening, before application, 90 min after application, 24 hours after application | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI |  | MRI-examination, before application, 90 min after application, 24 hours after application | 
| fMRI |  | fMRI-examination, before application, 90 min after application, 24 hours after application | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes mellitus, neuropathy, foot, sensibility, brain plasticity