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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: EMLA cream; Drug: EMLA cream

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 3

Contacts and Locations

Study Locations

• Sweden
  • Malmö, Sweden, SE-205 02
    • Department of Hand Surgery, Malmö University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EMLA cream	Drug: EMLA cream; 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.; Drug: EMLA cream; 50g applied according to description of intervention
Placebo Comparator: Placebo cream; A placebo cream identical in appearance and consistency to the experimental cream	Drug: EMLA cream; 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.; Drug: EMLA cream; 50g applied according to description of intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Lund University Hospital
• Investigators: Principal Investigator: Göran Lundborg, Professor, Dpt of Hand Surgery, Malmö University Hospital, Lund University, Sweden

Publications and helpful links

General Publications

• Lundborg GN, Bjorkman AC, Rosen BN, Nilsson JA, Dahlin LB. Cutaneous anaesthesia of the lower leg can improve sensibility in the diabetic foot. A double-blind, randomized clinical trial. Diabet Med. 2010 Jul;27(7):823-9. doi: 10.1111/j.1464-5491.2010.03014.x.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: August 12, 2009
• First Submitted That Met QC Criteria: August 13, 2009
• First Posted (Estimate): August 14, 2009

Study Record Updates

• Last Update Posted (Estimate): December 16, 2013
• Last Update Submitted That Met QC Criteria: December 13, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Diabetes mellitus; neuropathy; foot; sensibility; brain plasticity
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Anesthetics, Combined; Lidocaine, Prilocaine Drug Combination
• Other Study ID Numbers: 2008-001834-29