To study the inflammatory response (induration) to intracutaneous Candida albicans in healthy individuals, patients with diabetes without polyneuropathy, patients with diabetic polyneuropathy and patients with a history of Charcot neuro-…
ID
Source
Brief title
Condition
- Diabetic complications
- Bone disorders (excl congenital and fractures)
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
In all groups extent of induration as a response to intracutaneous Candida
albicans extract in four concentrations (1, 1:1,7, 1:5, 1:10) after 24, 48 and
72 hours.
Secondary outcome
Temperature difference between injection site of different concentrations of
Candida albicans on the foot and arm and the same location on the contralateral
foot and arm.
In 3 participants per group (with exception of the patients with a history of
Charcot neuro-osteoarthropathy) characterization of the induration and the
difference herein between the groups by skin biopsy.
Background summary
Foot ulcers and Charcot neuro-osteoarthropathy are feared complications of
diabetic polyneuropathy. Despite extensive tissue destruction (due to
infection), foot ulcers are often not accompanied by systemic signs of
inflammation. On the other hand, Charcot neuro-osteoarthropathy is
characterized by a clinical presentation of severe inflammation (a red, warm
and swollen foot). These distinct clinical presentations might be due to an
altered neurogenic regulation of the inflammatory response due to the existing
polyneuropathy.
A conducted pilot study demonstrated decreased type IV hypersensitivity
response to intracutaneous Candida albicans in patients with diabetic
polyneuropathy in comparison to patients with diabetes without polyneuropathy
and healthy controls. In one patient with a history of Charcot
neuro-osteoarthropathy, the response to intracutaneous Candida albicans was
exacerbated compared to patients with diabetes and healthy controls.
This leads us to hypothesize that the delayed hypersensitivity response to
intracutaneous Candida albicans is decreased in patients with diabetic
polyneuropathy as compared to patients with diabetes without polyneuropathy. On
the other hand, we hypothesize that the delayed hypersensitivity response to
intracutaneous Candida albicans is increased in patients with a history of
Charcot neuro-osteoarthropathy as compared to patients with diabetes with and
without polyneuropathy.
Study objective
To study the inflammatory response (induration) to intracutaneous Candida
albicans in healthy individuals, patients with diabetes without polyneuropathy,
patients with diabetic polyneuropathy and patients with a history of Charcot
neuro-osteoarthropathy.
Study design
Observational study
Intervention
Intracutaneous injection of Candida albicans extract in four concentrations (1,
1:1,7, 1:5, 1:10)
Study burden and risks
1 venous blood sample, 1 capillary blood sample and 1 urine sample will be
taken. Height, weight, pulse frequency and blood pressure will be measured.
Inspection and neurological examination of the lower extremities will be
performed. Conduction velocity of the n. suralis will be measured by
electromyography. Pulsations of the lower extremity arteries will be palpated
and the ankle-brachial index will be determined. The study requires 4 visits:
the first one lasting 75 minutes, the subsequent ones lasting 30 minutes. For
the patients in whom punch skin biopsies are taken the fourth visit will last
45 minutes. For the participants with polyneuropathy follow up visits after the
biopsy will be planned 1, 4 and 7 days after the biopsy. For the participants
without polyneuropathy follow up by telephone will be planned 4 days after the
biopsy. Intracutaneous injection of Candida albicans extract is associated with
short lasting mild discomfort at the injection site. Risks for participants
consist of an immediate hypersensitivity reaction to Candida albicans extract
(not observed in the conducted pilot study), wound infection at the biopsy site
and poor healing of the biopsy site in participants with polyneuropathy
(although this is unlikely considering a previously conducted study by Krishnan
et al published in Diabetes Care in 2007). There is a theoretical risk of an
anaphylactoid reaction as a response to the intracutaneous injection of Candida
albicans. This is however highly unlikely and has not been previously
described.
P Debeyelaan 25
6229 HX Maastricht
NL
P Debeyelaan 25
6229 HX Maastricht
NL
Listed location countries
Age
Inclusion criteria
Patients with type 2 diabetes with and without polyneuropathy aged 40-75 years. The presence of polyneuropathy is assessed by means of the Valk score and measurement of the conduction velocity in the n. suralis.
Patients with type 2 diabetes with a history of Charcot*s disease aged 40-75 years.
Healthy controls aged 40-75 years.
Signed informed consent.
Exclusion criteria
Peripheral arterial disease.
Active Charcot's disease.
Renal insufficiency.
Systemic disease.
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.
Use of medication for asthma.
Impaired immunity.
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.
History of anaphylaxis.
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
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT01370837 |
| CCMO | NL37123.068.11 |