The Effects of Topical Corticosteroid Use on Insulin Sensitivity and Bone Turnover

Study Overview
=================
Brief Summary
-----------------
The investigators believe that the emerging epidemiological evidence connecting topical use of corticosteroids to the development of type 2 diabetes and osteoporosis point to potentially massive, yet clinically unacknowledged problems associated with topical corticosteroid treatment. Using state-of-the-art methodology, the present study will delineate the impact of topical corticosteroid use on insulin sensitivity and bone turnover markers in patients with atopic dermatitis and, thus, provide important data that may have implications for millions of people using topical corticosteroids.

Official Title
-----------------
The Effects of Topical Corticosteroid Use on Insulin Sensitivity and Bone Turnover

Conditions
-----------------
Atopic Dermatitis, Atopic Eczema

Intervention / Treatment
-----------------
* Drug: Betnovate, betamethasone dipropionate ointment 0.1% and placebo
* Drug: Protopic, tacrolimus ointment 0.1%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Age 18-75 years AD according to the Hanifin and Rajka Criteria24 AD for at least 3 years BMI ≤ 30 kg/m2 Haemoglobin A1c (HbA1c) ≤ 42 mmol/mol (6.0%) Normal haemoglobin (men: 8.3-10.5 mmol/L and women 7.3-9.5 mmol/L. A 5% deviation will be allowed if the patient besides this is healthy) Informed consent In general patients should not be diagnosed with diseases that may affect or be affected by the study/treatment (evaluated by a doctor) (such as untreated skin infections, acne vulgaris (beside face region), a skin barrier defect, such as Netherton's syndrome, lamellar ichthyosis, generalized erythroderma or cutaneous Graft Versus Host Disease, congenital or acquired immunodeficiencies or in patients on therapy that cause immunosuppression, and Protopic ointment should not be applied to lesions that are considered to be potentially malignant or pre-malignant. Further patients should not suffer from kidney or liver disease/insufficiency. See the SPC for Protopic and Betnovate.) Exclusion criteria Diagnosed diabetes mellitus Other chronic inflammatory diseases (including but not limited to rheumatoid arthritis, inflammatory bowel disease etc) beside AD and non-treatment demanding rhinitis or asthma (treated within the last 4 weeks) Pregnancy (a urine test will be done at every visit and birth control is required, see below*) Breast feeding Treatment with drugs that might affect the glucose metabolism beside TCS within a month prior to the project Daily smoker, alcoholic, or drug abuser Hypersensitivity to Protopic or Betnovate

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomised, two-arm, active comparator, double-dummy, double-blinded trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Betamethasone-17-valerat + placebo ointment<br>Atopic dermatitis patients: topical treatment with twice daily full-body ointment containing corticosteroid (Betnovate, betamethasone dipropionate ointment 0.1%) and placebo | Drug: Betnovate, betamethasone dipropionate ointment 0.1% and placebo<br>* Explore the systemic effects of Betnovate<br>|
| Active Comparator: Tacrolimus ointment<br>Atopic dermatitis patients: topical treatment with twice daily full-body ointment containing calcineurin inhibitor (Protopic, tacrolimus ointment 0.1%) | Drug: Protopic, tacrolimus ointment 0.1%<br>* Compare the systemic effects of Betnovate to Protopic<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in whole-body insulin sensitivity | Change in whole-body insulin sensitivity during treatment with topical corticosteroid use compared to the control group treated with topical calcineurin inhibitors. Insulin sensitivity will be assessed by the hyperinsulinaemic euglycaemic clamp method with glucose and glycerol tracer and indirect calorimetry (rate of disappearance (Rd)). | Baseline, after 14 days daily treatment, and after 4 weeks of twice daily treatment twice weekly | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
topical corticosteroids, topical calcineurin inhibitors