Vitamin D Supplementation in Polymorphic Light Eruption (VitD-PLE_2012)

• ClinicalTrials.gov Identifier: NCT01595893
• Recruitment Status: Terminated
• First Posted: May 10, 2012
• Last Update Posted: June 13, 2016
• Sponsor: Medical University of Graz
• Collaborator: Austrian Science Fund (FWF)
• Information provided by (Responsible Party): Medical University of Graz

Study Description

Brief Summary:

Polymorphic light eruption (PLE) is a common photodermatosis with a high prevalence of approximately 11 to 21% in the population. Similar to lupus erythematosus (LE), an UV-inducible systemic autoimmune disease, PLE has a female preponderance with a mean onset in the second to third decade of life. PLE lesions are very itchy and typically appear on sun-exposed body sites in spring or early summer. The quality of life in patients with PLE is often severely disturbed, as evidenced by high levels of anxiety and depression. For prophylaxis besides conventional sunscreens, photo(chemo)therapy is effective in many cases, when administered over several weeks for hardening in early spring before the first natural sun exposure takes place. However, because prolonged treatment with UVB and/or photochemotherapy is potentially carcinogenic, the search for pathogenic mechanisms and new treatment options in PLE is ongoing. The exact pathogenesis of PLE is currently unknown but findings suggest an autoimmune-type background with resistance to UV-induced immune suppression and simultaneous immune reactions against skin photo-neoantigens. The investigators have recently found that PLE patients had significantly reduced 1,25-(OH)2-vitamin D3 serum levels (13-14ng/ml) compared to the normal population (>30ng/ml). In addition, the investigators were able to demonstrate in an intra-individual half-body trial that topical administration of an immunostimulatory 1,25-(OH)2-vitamin-D3 analogue calcipotriol reduced PLE symptoms in an experimental study. In the proposed randomized double-blinded placebo-controlled trial the investigators attempt to study the effect of oral vitamin D3 supplementation (2 x 40.000 IE, given orally two weeks apart) on PLE symptoms.

Condition or disease	Intervention/treatment	Phase
Polymorphic Light Eruption	Drug: Oral Vitamin D 3; Drug: Miglyol 812 N	Phase 3

Detailed Description:

PLE patients will be subjected to experimental photo provocation with solar simulated UV radiation over several days before and after vitamin D3 supplementation. Disease symptoms will be quantified with a newly established and validated PLE test score, (AA + SI + 0.4P [range, 0-12], where AA is affected area score [range, 0-4], SI is skin infiltration score [range, 0-4], and P is pruritus score on a visual analogue scale [range, 0-10]). Optional biopsies will be taken to investigate the effect of oral vitamin D3 on UV-induced skin test sites, including cellular skin infiltration and expression and release of cytokines in situ as endpoints. We will also study the effect of oral vitamin D3 on abnormalities i) of levels and function of regulatory T cells, ii) chemotaxis of leucocytes, and iii) proinflammatory cytokines, i.e. alterations that have been previously linked to PLE pathogenesis. This will be done by i) FACS and co-culture T cell proliferation assays, ii) response of peripheral neutrophil leucocytes to the chemoattractants leukotriene B4 (LTB4) and formyl-methionyl-leucyl-phenylalanine, and iii) ELISA and immunobead assay of patient serum.

To back-up the results obtained with the PLE test score upon experimental photo provocation the study participants will receive a questionnaire on PLE symptoms and quality of life, adapted from scores as previously described. This questionnaire will allow monitoring PLE symptoms and quality of life in the patients during the summer season following the oral vitamin D3 supplementation in spring.

The results of the project will enlighten the mechanism of PLE and may establish the base of a novel prevention strategy via the vitamin D3 pathway.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Vitamin D3 Supplementation in Polymorphic Light Eruption: Randomized Double-blinded Placebo-controlled Trial
• Study Start Date: April 2012
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: May 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vitamin D3	Drug: Oral Vitamin D 3; 40,000 IE vitamin D3 per 70 kg body weight, given twice (2 weeks apart); Other Name: Oleovit D3, Fresenius Kabi, Austria
Placebo Comparator: Placebo	Drug: Miglyol 812 N; Neutral oil of esters extracted from coconut and palm kernel; Other Name: Vegetable oil

Outcome Measures

Primary Outcome Measures :

1. PLE test score (from 0-12) of experimental photo provocation [ Time Frame: At day 2, 3, 4, 5, and 8 (change from baseline) ]
   See study description.

Secondary Outcome Measures :

1. Cytokine levels in serum [ Time Frame: At day 22 and 36; and at month 4-8 ]
2. Chemotaxis of neutrophils [ Time Frame: At day 22 and 36; and at month 4-8 (compared to baseline) ]
3. Level of regulatory T cells [ Time Frame: At day 22 and 36; and at month 4-8 (compared to baseline) ]
4. Quantification of skin alterations, including cellular infiltration and cytokine profile [ Time Frame: Day 5 and 40 ]
5. Dermatological quality of life (DLQI) [ Time Frame: At month 4-8 ]
6. HADS (hospital anxiety and depression scale) [ Time Frame: At month 4-8 ]
7. Function of regulatory T cells [ Time Frame: 22 and 36; and at month 4-8 (compared to baseline) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Confirmed diagnosis of PLE by typical patient history, typical histology of skin lesions and/or positive photo provocation results

Exclusion Criteria:

• Allergy or intolerance to Oleovit D3 or Coconut/palm kernel
• Presence or history of malignant skin tumors
• Dysplastic melanocytic nevus syndrome
• Photosensitive diseases such as porphyria, chronic actinic dermatitis, xeroderma pigmentosum, and basal cell nevus syndrome; autoimmune disorders such as lupus erythematosus or dermatomyositis
• Sarcoid
• Renal dysfunction
• Psychiatric disorder
• Pregnancy or breastfeeding
• Topical treatment with vitamin D derivates within 3 months
• Oral treatment with vitamin D within 6 months
• Antinuclear antibodies such as anti-ds-DNA or anti- Ro/La
• 25-hydroxy vitamin D serum levels > 30ng/ml at screening visit
• Serum hypercalcemia > 2,65 nmol/L
• Treatment with thiazides or glycosides
• Systemic treatment with steroids and/or other immunosuppressive drugs within 4 weeks
• UV exposure in test fields within 8 weeks before the start of the study
• General poor health status

Contacts and Locations

Locations

Austria

Medical University of Graz, Department of Dermatology

Graz, Austria, A-8036

Sponsors and Collaborators

Medical University of Graz

Austrian Science Fund (FWF)

Investigators

• Principal Investigator: Peter Wolf, MD; Medical University of Graz

More Information

Additional Information:

Webpage of Research Unit 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Schweintzger NA, Gruber-Wackernagel A, Shirsath N, Quehenberger F, Obermayer-Pietsch B, Wolf P. Influence of the season on vitamin D levels and regulatory T cells in patients with polymorphic light eruption. Photochem Photobiol Sci. 2016 Mar;15(3):440-6. doi: 10.1039/c5pp00398a. Epub 2016 Feb 25.

• Responsible Party: Medical University of Graz
• ClinicalTrials.gov Identifier: NCT01595893
• Other Study ID Numbers: Graz 24-220 ex 11/12
• First Posted: May 10, 2012
• Last Update Posted: June 13, 2016
• Last Verified: June 2016

Keywords provided by Medical University of Graz:

Polymorphic light eruption; Vitamin D3; Photo provocation; Immune function

Additional relevant MeSH terms:

Exanthema; Dermatitis, Contact; Skin Diseases; Dermatitis; Skin Diseases, Eczematous; Vitamin D; Cholecalciferol; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents