Neurogenic Inflammation in Diabetes

Study Overview
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Brief Summary
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Polyneuropathy is a complication of diabetes mellitus which leads to decreased sensation in arms and legs. This in turn can lead to the development of (infected) foot ulcers. Charcot's disease can also be a consequence of polyneuropathy. Patients with Charcot's disease suddenly develop a red, warm and swollen foot, like an infection. Charcot's disease leads to foot fractures. After these fractures have healed, the shape of the foot can be dramatically altered. This altered shape of the foot increases the risk of developing foot ulcers. Nerves are important in regulating the inflammatory response. This study aims to investigate whether the inflammatory response is different in patients with polyneuropathy with and without a history of Charcot's disease.

Official Title
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Neurogenic Inflammation in Diabetic Polyneuropathy and Charcot Neuro-osteoarthropathy: Response to Intracutaneous Candida Albicans

Conditions
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Diabetes Mellitus, Polyneuropathies, Arthropathy, Neurogenic

Intervention / Treatment
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* Other: Intracutaneous injection of Candida albicans antigen.
* Other: Temperature measurement.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 2 diabetes with and without polyneuropathy. Patients with type 2 diabetes with a history of Charcot's disease. Healthy controls. Signed informed consent. Exclusion Criteria: Peripheral arterial disease: toe pressure < 70 mm Hg and/or transcutaneous oxygen tension < 40 mm Hg and/or claudication. Renal insufficiency: MDRD creatinin clearance < 30 ml/min. Systemic disease such as vasculitis or rheumatoid arthritis. Malignancy. (Diabetic) foot ulcer. Gout. Bacterial infection of an extremity. Skin condition of the dorsal aspect of the foot or the medial side of the upper arm. Bleeding disorder such as hemophilia. Use of medication for asthma. Impaired immunity such as in HIV/AIDS. Capillary blood glucose < 3 mmol/l or > 20 mmol/l at the time of the study. Peripheral oedema. Vaccination in the two months prior to study inclusion. Chemotherapy or radiation therapy in the twelve months prior to study inclusion. Surgery in the two months prior to study inclusion. Previous adverse reaction to Candida albicans antigen. Acute infection at the time of the study or in the month prior to study inclusion. Transfusion in the two months prior to study inclusion. Use of immunosuppressants in the two months prior to study inclusion. Pregnancy or breastfeeding.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy controls<br> | Other: Intracutaneous injection of Candida albicans antigen.<br>* Intracutaneous injection of 0.05 ml of four different concentrations of Candida albicans antigen on both the arm and foot.<br>Other: Temperature measurement.<br>* Temperature measurement at the site of injection of the highest concentration of Candida albicans antigen on the foot and the same location on the contralateral foot using an infrared thermometer.<br>|
| Experimental: Diabetes<br>Patients with diabetes mellitus without polyneuropathy. | Other: Intracutaneous injection of Candida albicans antigen.<br>* Intracutaneous injection of 0.05 ml of four different concentrations of Candida albicans antigen on both the arm and foot.<br>Other: Temperature measurement.<br>* Temperature measurement at the site of injection of the highest concentration of Candida albicans antigen on the foot and the same location on the contralateral foot using an infrared thermometer.<br>|
| Experimental: Polyneuropathy<br>Patients with diabetes and polyneuropathy. | Other: Intracutaneous injection of Candida albicans antigen.<br>* Intracutaneous injection of 0.05 ml of four different concentrations of Candida albicans antigen on both the arm and foot.<br>Other: Temperature measurement.<br>* Temperature measurement at the site of injection of the highest concentration of Candida albicans antigen on the foot and the same location on the contralateral foot using an infrared thermometer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induration Size as a Response to Intracutaneous Candida Albicans. |  | 48 hours after injection. |