Analysis of Response of Subjects With Atopic Dermatitis or Psoriasis to Oral Vitamin D3

Study Overview
=================
Brief Summary
-----------------
This study will examine whether administration of oral Vitamin D3 given over 21 days will change the antimicrobial peptide expression in the skin or saliva of subjects with Atopic Dermatitis (AD). This study will help researchers determine if the lack of the expression of antimicrobial peptides in individuals with AD plays a role in the susceptibility to eczema vaccinatum (EV).

Detailed Description
-----------------
Atopic Dermatitis (AD) is a chronic inflammatory skin disorder in which the skin becomes extremely itchy and is susceptible to recurrent skin infections. AD is thought to occur from a combination of immunological, genetic, and environmental factors. Individuals with AD are at risk for developing a severe and widely disseminated infection called eczema vaccinatum (EV). EV is caused when the live attenuated vaccinia virus in the vaccine reproduces and spreads throughout the body. Individuals with AD lack certain antimicrobial peptides, specifically cathelicidins. This trial also includes a sub-study with individuals who have psoriasis. Psoriasis is also an immune-mediated skin disease, and is characterized by scaling skin and inflammation (pain, swelling, heat, and redness). Most psoriasis cause patches of thick, red skin with silvery scales. These patches can itch or feel sore. This sub-study will provide additional information on psoriatic responses to oral vitamin D. (Originally listed separately as ADVN-CATH-03-01).

Official Title
-----------------
Analysis of the Response of Subjects With Atopic Dermatitis to Oral Vitamin D3 by Measurement of Antimicrobial Peptide Expression in Skin and Saliva

Conditions
-----------------
Atopic Dermatitis, Psoriasis

Intervention / Treatment
-----------------
* Drug: Vitamin D3
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria (Main Study): Definitive diagnosis of AD for at least 6 months, stringently diagnosed using the ADVN Standard Diagnostic Criteria, and has lesional skin present OR is a non-atopic healthy control subject with no personal or family history of food allergy, AD, asthma, or allergic rhinitis Residing in the US. Inclusion Criteria (Sub-Study): Definitive diagnosis of typical plaque psoriasis for at least 6 months, stringently diagnosed using the ADVN Standard Diagnostic Criteria; or is an AD or non-atopic healthy control subject participating in the main protocol ADVN CATH 03. Residing in the US. Exclusion Criteria (Main Study): Presence of atopy without stringent AD features, allowing only a presumptive diagnosis of AD Presence of AD with exfoliative erythroderma Presence of psoriasis Pregnant or lactating females Existence of ongoing dental disease (e.g., gingivitis) History of bleeding disorders Presence of severe AD that would be exacerbated by withholding of topical corticosteroids, oral or topical antibiotics, topical or systemic antihistamines, oral antivirals, immune enhancers (e.g., imiquimod), or topical calcineurin inhibitors within 7 days of Study Visit 2 (Baseline) and throughout the course of the trial Receiving systemic immunosuppressives, chemotherapeutic agents, anti-inflammatory biologics (e.g., alefacept, etanercept), systemic, oral, injectable or inhaled steroids, vitamin D supplements (more than 400 IU daily) or oral calcineurin inhibitors 30 days prior to the Study Visit 2 (Baseline) or anytime during the course of the trial Using topical corticosteroids, oral or topical antibiotics, oral antivirals, immune enhancers (e.g., imiquimod), topical or systemic antihistamines, or topical calcineurin inhibitors within 7 days of Study Visit 2 (Baseline) and during the course of the trial Receiving phototherapy (e.g., UVB, psoralen plus ultraviolet light A [PUVA]) within 30 days of Study Visit 2 (Baseline) and during the course of the trial Having autoimmune or immunodeficiency disease Presence of active systemic fungal (excluding nail fungus), bacterial, or viral infections History of or presence of active systemic malignancy, excluding uncomplicated non-melanoma skin cancer Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements Inability or unwillingness of a participant to give written informed consent Diabetes Certain screening laboratory values not within normal limits, which would include calcium, serum PTH, and serum creatinine History of kidney disease or kidney stones Currently taking barbiturates such as phenobarbital (Luminal) Currently taking carbamazine (Tegretol), digoxin, phenytoin (Dilantin) or fosphenytoin (cerebyx) Currently taking diuretics such as thiazide diuretics, calcium channel blockers, or beta-blockers Currently taking magnesium-containing antacids, mineral oil, cholestyramine (Questran), colestipol(Colestid), orlistat (xenical), the fat substitute Olestra, cod liver oil, fish oil, or omega 3 fatty acids Currently taking oral antifungals such as ketoconazole History of serious or life-threatening anaphylactic reaction to tape or adhesives Lidocaine allergy History of or active hyperparathyroidism, sarcoid, tuberculosis or lymphoma. Exclusion Criteria (Sub-Study): Presence of AD with exfoliative erythroderma Presence of psoriasis with exfoliative erythroderma or presence of guttate psoriasis, primary palmoplantar psoriasis, or pustular psoriasis Pregnant or lactating females Existence of ongoing dental disease (e.g., gingivitis) History of bleeding disorders Presence of psoriasis that would be severely exacerbated by withholding topical corticosteroids, oral or topical antibiotics, topical or systemic antihistamines, oral antivirals, immune enhancers (e.g.,imiquimod), or topical calcineurin inhibitors within 7 days of Study Visit 2 (Baseline) and throughout the course of the trial Receiving systemic immunosuppressives, chemotherapeutic agents, anti-inflammatory biologics (e.g., alefacept, etanercept), systemic, oral, injectable, or inhaled steroids, vitamin D supplements (more than 400 IU daily), or oral calcineurin inhibitors, 30 days prior to the Study Visit 2 (Baseline) or anytime during the course of the trial Using topical corticosteroids, oral or topical antibiotics, oral antivirals, immune enhancers (e.g., imiquimod), topical or systemic antihistamines, or topical calcineurin inhibitors within 7 days of Study Visit 2 (Baseline) and during the course of the trial Receiving phototherapy (e.g., UVB, psoralen plus ultraviolet light A [PUVA]) within 30 days of Study Visit 2 (Baseline) and during the course of the trial Having autoimmune or immunodeficiency disease Presence of active systemic fungal (excluding nail fungus), bacterial, or viral infections History of or presence of active systemic malignancy, excluding uncomplicated non-melanoma skin cancer Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements Inability or unwillingness of a participant to give written informed consent Diabetes Screening laboratory values not within normal limits, which would include calcium, serum PTH, and serum creatinine History of kidney disease or kidney stones Currently taking barbiturates such as phenobarbital (Luminal) Currently taking carbamazepine (Tegretol), digoxin, phenytoin (Dilantin) or fosphenytoin (cerebyx) Currently taking diuretics such as thiazide diuretics, calcium channel blockers, or beta-blockers Currently taking magnesium-containing antacids, mineral oil, cholestyramine (Questran), colestipol (Colestid), orlistat (xenical), the fat substitute Olestra, cod liver oil, fish oil, or omega 3 fatty acids Currently taking oral antifungals such as ketoconazole History of serious or life-threatening anaphylactic reaction to tape or adhesives Lidocaine allergy History of or active hyperparathyroidism, sarcoid, tuberculosis or lymphoma.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3<br>Subjects received a 21-day course of oral vitamin D3 (cholecalciferol, 4,000 international units [IU] | Drug: Vitamin D3<br>* Administration of oral vitamin D3 at 4000IU<br>* Other names: cholecalciferol;|
| Placebo Comparator: Placebo<br>Subjects received a 21-day course of oral vitamin D3-placebo | Drug: Placebo<br>* Administration of oral Vitamin D3 placebo<br>* Other names: vitamin D3 placebo;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on Day 21 in Relative Abundance of CAMP mRNA in Lesional and Non-Lesional Skin for Atopic Dermatitis (AD) Participants Who Received Oral Vitamin D3 Versus Vitamin D3-Placebo | Cathelicidin (CAMP) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. Cathelicidin amount is clinically significant as it is necessary to resist infection. Cathelicidin amount is not known to be clinically relevant to the clinical signs of dermatitis associated with AD. | Baseline to Day 21 | 
| Change From Baseline on Day 21 in Relative Abundance of CAMP mRNA in Non-Lesional Skin for Non-Atopic Dermatitis (Non-AD) Participants Who Received Oral Vitamin D3 Versus Vitamin D3-Placebo | Cathelicidin (CAMP) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. Non-AD is defined as a healthy volunteer without atopic dermatitis, therefore the lesional skin-type was not measured in this group. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. Cathelicidin amount is clinically significant as it is necessary to resist infection. Cathelicidin amount is not known to be clinically relevant to the clinical signs of dermatitis associated with AD. | Baseline to Day 21 | 
| Change From Baseline on Day 21 in Relative Abundance of CAMP mRNA in Lesional and Non-Lesional Skin for Psoriatic Participants Who Received Vitamin D3 Versus Vitamin D3-Placebo | Cathelicidin (CAMP) messenger ribonucleic acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline, Cathelicidin abundance in psoriasis has been hypothesized to correlate with increased inflammation. No direct clinical correlation is known. | Baseline to Day 21 | 
| Change From Baseline on Day 21 in Relative Abundance of HBD-3 mRNA in Lesional and Non-Lesional Skin for Atopic Dermatitis (AD) Participants Who Received Oral Vitamin D3 Versus Vitamin D3-Placebo | Human Beta-defensin 3 (HBD-3) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies as measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. HBD-3 amount is clinically significant as it is necessary to resist infection. HBD-3 amount is not known to be clinically relevant to the clinical signs of dermatitis associated with AD. | Baseline to Day 21 | 
| Change From Baseline on Day 21 in Relative Abundance of HBD-3 mRNA in Non-Lesional Skin for Non-Atopic Dermatitis (Non-AD) Participants Who Received Oral Vitamin D3 Versus Vitamin D3-Placebo | Human Beta-defensin 3 (HBD-3) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. Non-AD is defined as a healthy volunteer without atopic dermatitis, therefore the lesional skin-type was not measured in this group. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. HBD-3 amount is clinically significant as it is necessary to resist infection. HBD-3 amount is not known to be clinically relevant to the clinical signs of dermatitis associated with AD. | Baseline to Day 21 | 
| Change From Baseline on Day 21 in Relative Abundance of HBD-3 mRNA in Lesional and Non-Lesional Skin for Psoriatic Participants Who Received Vitamin D3 Versus Vitamin D3-Placebo | Human Beta-defensin 3 (HBD-3) Messenger Ribonucleic acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. There is no known clinical correlation between HBD-3 and psoriasis. | Baseline to Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on Day 21 in Relative Abundance of IL-13 mRNA in Lesional and Non-Lesional Skin for Atopic Dermatitis (AD) Participants Who Received Vitamin D3 Versus Vitamin D3-Placebo | Cytokine interleukin-13 (IL-13) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. A decrease in IL-13 may be clinically correlated with improvement of AD. | Baseline to Day 21 | 
| Change From Baseline on Day 21 in Relative Abundance of IL-13 mRNA in Non-Lesional Skin for Non-Atopic Dermatitis (Non-AD) Participants Who Received Vitamin D3 Versus Vitamin D3-Placebo | Cytokine interleukin-13 ( IL-13) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. Non-AD is defined as a healthy volunteer without atopic dermatitis. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. A decrease in IL-13 may be clinically correlated with improvement of AD. | Baseline to Day 21 | 
| Change From Baseline on Day 21 in Relative Abundance of IL-13 mRNA in Lesional and Non-Lesional Skin for Psoriatic Participants Who Received Vitamin D3 Versus Vitamin D3-Placebo | Cytokine interleukin-13 ( IL-13) Messenger Ribonucleic Acid (mRNA) expression from skin biopsies measured by quantitative real time polymerase chain reaction (qRT-PCR). Average delta cycle threshold (CT) adjusted for non-atopic average at baseline on the arithmetic scale = [(average of (CT for CAMP - CT for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) across replicates) - (the average of (CT for CAMP - CT for GAPDH) for non-atopic subjects at baseline)]. A negative value indicates a drop from baseline and a positive value indicates an increase from baseline. There is no known clinical correlation between IL-13 and psoriasis. | Baseline to Day 21 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vitamin D3, Atopic Dermatitis, Antimicrobial Peptide Expression