Arthropathy, Neurogenic, Diabetes Mellitus, Polyneuropathies
Conditions
Brief summary
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.
Interventions
OTHERIntracutaneous injection of Candida albicans antigen.
Intracutaneous injection of 0.05 ml of four different concentrations of Candida albicans antigen on both the arm and foot.
OTHERTemperature measurement.
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.
Sponsors
Dutch Diabetes Research Foundation
Maastricht University Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Induration Size as a Response to Intracutaneous Candida Albicans. | 48 hours after injection. |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Controls Intracutaneous injection of Candida albicans antigen.: Intracutaneous injection of 0.05 ml of four different concentrations of Candida albicans antigen on both the arm and foot.
Temperature measurement.: 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. | 12 |
| Diabetes Patients with diabetes mellitus without polyneuropathy.
Intracutaneous injection of Candida albicans antigen.: Intracutaneous injection of 0.05 ml of four different concentrations of Candida albicans antigen on both the arm and foot.
Temperature measurement.: 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. | 12 |
| Polyneuropathy Patients with diabetes and polyneuropathy.
Intracutaneous injection of Candida albicans antigen.: Intracutaneous injection of 0.05 ml of four different concentrations of Candida albicans antigen on both the arm and foot.
Temperature measurement.: 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. | 17 |
| Total | 41 |
Baseline characteristics
| Characteristic | Healthy Controls | Diabetes | Polyneuropathy | Total |
|---|---|---|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 8.8 | 65 years STANDARD_DEVIATION 6.7 | 66 years STANDARD_DEVIATION 5.2 | 64 years STANDARD_DEVIATION 7.3 |
| Region of Enrollment Netherlands | 12 participants | 12 participants | 17 participants | 41 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 14 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 12 | 0 / 17 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 1 / 17 |
Outcome results
Primary
Induration Size as a Response to Intracutaneous Candida Albicans.
Time frame: 48 hours after injection.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Healthy Controls | Induration Size as a Response to Intracutaneous Candida Albicans. | Arm | 4 millimeters |
| Healthy Controls | Induration Size as a Response to Intracutaneous Candida Albicans. | Foot | 4 millimeters |
| Diabetes | Induration Size as a Response to Intracutaneous Candida Albicans. | Arm | 6 millimeters |
| Diabetes | Induration Size as a Response to Intracutaneous Candida Albicans. | Foot | 2 millimeters |
| Polyneuropathy | Induration Size as a Response to Intracutaneous Candida Albicans. | Arm | 5 millimeters |
| Polyneuropathy | Induration Size as a Response to Intracutaneous Candida Albicans. | Foot | 0 millimeters |
Comparison: Armp-value: 0.84Kruskal-Wallis
Comparison: Footp-value: 0.76Kruskal-Wallis
Comparison: Armp-value: 0.53Kruskal-Wallis
Comparison: Footp-value: 0.07Kruskal-Wallis
Comparison: Arm vs footp-value: 0.25Wilcoxon (Mann-Whitney)
Comparison: Arm vs footp-value: 0.27Wilcoxon (Mann-Whitney)
Comparison: Arm vs footp-value: <0.01Wilcoxon (Mann-Whitney)