PRAgmatic Trial in Atopic Dermatitis Testing Long-term Control Effectiveness of New Phototherapy Regimen During Winter Coupled With Oral Vitamin D Supplementation vs. Placebo

Study Overview
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Brief Summary
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Spaced phototherapy sessions during winter as add-on therapy in combination with vitamin D supplementation or not, could be beneficial to improve disease LTC in AD patients

Detailed Description
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The major therapeutic challenge in patient with Atopic Dermatitis is long-term control of disease activity (LTC), for which the current TAT-based pro-active strategy does not meet all the needs. Phototherapy is a good candidate: it is widely used as a second-line treatment in AD with demonstrated efficacy. However, only short-term control has been evaluated; and only 2-3 times a week intensive schedules have been tested and are used in current practice. A novel phototherapy regimen would be required for disease LTC, allowing a trade-off between disease control, UV-induced risks, and patient adherence. Vitamin D supplementation is another good candidate: several studies have shown lower serum levels of vitamin D to be correlated with more severe AD; and three short-term, low-power low-quality, placebo-controlled randomised trials testing vitamin D supplementation yielded conflicting results, leaving its therapeutic efficacy undecided for short-term control, and unknown for LTC.

Official Title
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Multicentre, Cross-over, PRAgmatic Trial in Atopic Dermatitis Testing Long-term Control Effectiveness of New Phototherapy Regimen During Winter as an add-on Therapy, Coupled With Oral Vitamin D Supplementation vs. Placebo in a Randomised, Parallel-group Trial

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Cholecalciferol
* Drug: Placebo of cholecalciferol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with atopic dermatitis (Hanifin and Rajka criteria), Aged 15 years or more, With > 2 years of disease evolution, With moderate-to-severe disease (IGA > 2), Patients that have received TAT for at least 12 weeks and have symptoms requiring an increase in therapy, Seasonality in disease severity (based on a questionnaire assessing disease improvement during summer), Easy access to a phototherapy cabin (widely implanted in primary care dermatology private practice in France), Effective contraception to be used at least 30 days before initiation of treatment, during treatment and 29 weeks after last administration for women of reproductive age, Written informed consent of the patient For patients aged between 15 and 18, written informed consent of the parents and of the teenager. Exclusion Criteria: Any cause of contra-indication for vitamin D supplementation: flare of granulomatosis, primary hyperparathyroidism, Clinical suspicion of hypercalciuria, Indication to a systemic immunosuppressant in the next 2 years, Atopic dermatitis known to be aggravated by UV exposure, Any contra-indication for artificial or solar exposure including: genetic diseases with a predisposition to skin cancer, any history of personal skin cancer (melanoma, squamous cell skin cancer, basal cell skin cancer), lupus, dermatomyositis, any other photosensitizing skin disease, photosensitizing medication (see appendix 2), More than 100 previous phototherapy sessions in lifetime, Pregnancy or breastfeeding, Persons subject to major legal protection (safeguarding justice, guardianship, trusteeship), persons deprived of liberty.

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cholecalciferol<br>Administration of cholecalciferol every 3 months during 2 years combined with new phototherapy regimen during winter (phototherapy winter 1, observation winter 2 or the opposite) | Drug: Cholecalciferol<br> <br> * Other names: Uvedose;|
| Placebo Comparator: Placebo of cholecalciferol<br>Administration of placebo of cholecalciferol every 3 months during 2 years combined with new phototherapy regimen during winter (phototherapy winter 1, observation winter 2 or the opposite) | Drug: Placebo of cholecalciferol<br> <br> * Other names: Placebo of Uvedose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hierarchical criterion based on repeated measures of PO-SCORAD severity score | Measurement of PO-SCORAD score | 2 years | 
| Hierarchical criterion based on cumulative consumption of topical anti-inflammatory treatments (collected tubes) during winter | Measurement of cumulative consumption of topical anti-inflammatory treatments | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of desease severity | Assessment of desease severity by EASI score | 2 years | 
| Assessment of desease severity | Assessment of desease severity by IGA score | 2 years | 
| Assessment of desease severity | Assessment of desease severity by SCORAD score | 2 years | 
| Assessment of desease severity | Assessment of desease severity by POEM score | 2 years | 
| Assessment of the quality of life | Assessment of the quality of life by DLQI score | 2 years | 
| Measurement of serum Vitamin D (25-(OH)-vitamin D) |  | 2 years | 
| Measurement of total IgE serum |  | 2 years | 
| Assessement of number of weeks of well-controlled atopic dermatitis |  | 2 years | 
| Assessment of inter-visit cumulative consumption of topical anti-inflammatory treatments |  | 2 years | 
| Assessment of patient satisfaction |  | 2 years |