Clinical trial NCT00789880: Analysis of Response of Subjects With Atopic Dermatitis or Psoriasis to Oral Vitamin D3
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Dermatitis
Psoriasis
Keywords: Vitamin D3
Atopic Dermatitis
Antimicrobial Peptide Expression
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Consortium of Food Allergy Research
First posted: 2008-11-13
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: 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
timeFrame: Baseline to Day 21
measure: 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
timeFrame: Baseline to Day 21
measure: 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
timeFrame: Baseline to Day 21
measure: 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
timeFrame: Baseline to Day 21
measure: 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
timeFrame: Baseline to Day 21
measure: 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
timeFrame: Baseline to Day 21
Secondary outcomes:
measure: 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
timeFrame: Baseline to Day 21
measure: 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
timeFrame: Baseline to Day 21
measure: 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
timeFrame: Baseline to Day 21
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: University of California, San Diego
name: Richard Gallo, MD, PhD
role: STUDY_CHAIR
References:
citation: Schauber J, Dorschner RA, Yamasaki K, Brouha B, Gallo RL. Control of the innate epithelial antimicrobial response is cell-type specific and dependent on relevant microenvironmental stimuli. Immunology. 2006 Aug;118(4):509-19. doi: 10.1111/j.1365-2567.2006.02399.x.
citation: Hata TR, Audish D, Kotol P, Coda A, Kabigting F, Miller J, Alexandrescu D, Boguniewicz M, Taylor P, Aertker L, Kesler K, Hanifin JM, Leung DY, Gallo RL. A randomized controlled double-blind investigation of the effects of vitamin D dietary supplementation in subjects with atopic dermatitis. J Eur Acad Dermatol Venereol. 2014 Jun;28(6):781-9. doi: 10.1111/jdv.12176. Epub 2013 May 3.