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

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators:	Food and Drug Administration (FDA) National Jewish Health University of California, San Diego Oregon Health and Science University
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00789880

Purpose

Atopic Dermatitis (AD) is a skin disorder in which people often have swelling and skin infection. People with this disease cannot receive the smallpox vaccine because it could cause them to have a fatal reaction known as eczema vaccinatum (EV). AD subjects have a lack of antimicrobial peptides (AMPs) under inflammatory conditions. This study will examine whether administration of oral Vitamin D3 will change the AMP expression in skin or saliva of AD subjects and healthy controls.

Condition	Intervention	Phase
Atopic Dermatitis	Drug: Vitamin D3 Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment
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

Resource links provided by NLM:

MedlinePlus related topics: Smallpox

Drug Information available for: Cholecalciferol Vitamin D

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Difference in change in expression of antimicrobial peptides (hCAP18/LL-37, HBD3) from baseline to study day 21 AD subjects' lesional and non-lesional skin biopsies. compared to change in expression of antimicrobial peptides from baseline to study day 21 [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Expression of antimicrobial peptides (hCAP18/LL-37, HBD3) at baseline and study day 21 in AD subjects' lesional and non-lesional skin biopsies. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ] [ Designated as safety issue: No ]
Expression of antimicrobial peptides (hCAP18/LL-37, HBD3) at baseline and study day 21 in non-AD subjects' skin biopsies. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ] [ Designated as safety issue: No ]
Change in expression of systemic antimicrobial peptides (hCAP18/LL-37, HBD3) from baseline to study day 21 in AD and non-AD subjects' saliva. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ] [ Designated as safety issue: No ]
Change in expression of TH2 cytokines IL-13 and IL-4 from baseline and study day 21 in AD subjects' lesional and non-lesional skin biopsies. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ] [ Designated as safety issue: No ]
Change in expression of TH2 cytokines IL-13 and IL-4 from baseline and study day 21 in non-AD subjects' skin biopsies. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ] [ Designated as safety issue: No ]
Change in expression of serum total IgE and RAST in AD and non-AD serum. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ] [ Designated as safety issue: No ]
Change in EASI score from baseline and study day 21 in AD subjects. [ Time Frame: Study Visit 2/Baseline through Study Visit 3/Day 21 ] [ Designated as safety issue: No ]
The proportion of subjects in each arm who experience any Grade 3 or higher adverse events over the duration of follow-up in this trial. [ Time Frame: Throughout study and follow-up ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	December 2008
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Administration of oral Vitamin D3: 4000IU capsule	Drug: Vitamin D3 4000IU
2: Experimental Administration of placebo	Drug: Placebo Placebo for Vitamin D3

Detailed Description:

AD is a chronic inflammatory skin disorder characterized by recurrent viral skin infections. AD subjects have a lack of antimicrobial peptides, specifically cathelicidins, under inflammatory conditions. 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 AD subjects and healthy controls. This study will provide information if the lack of expression of antimicrobial peptides in AD subjects could be a component of their susceptibility to EV.

An individual's participation in the study will last approximately one month. Participants will be randomized into one of two arms. Arm 1 will consist of 30 subjects (AD or healthy controls). They will receive Vitamin D3 4000IU capsules to take for 21 days (one capsule per day). Arm 2 will consist of 30 subjects (AD or healthy controls). They will receive placebo capsules to take for 21 days (one capsule per day).

This study will consist of 3 visits over the one-month period after enrollment.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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
18 to 70 years of age

Exclusion Criteria:

Under 18 or over 70 years of age
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., imiquod), 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 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 pheonobarbital (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), oristat (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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00789880

Contacts

Contact: Tissa Hata, MD

(858) 657-7096

thata@ucsd.edu

Locations

United States, California
University of California, San Diego	Recruiting
San Diego, California, United States
Contact: Jeremiah Miller 858-657-7192 jam011@ucsd.edu
Principal Investigator: Richard Gallo, MD, PhD
Sub-Investigator: Tissa Hata, MD
United States, Colorado
National Jewish Health	Recruiting
Denver, Colorado, United States
Contact: Judy Lairsmith 303-270-2413 lairsmithj@NJHealth.org
Principal Investigator: Donald Leung, MD, PhD
United States, Oregon
Oregon Health & Science University	Recruiting
Portland, Oregon, United States
Contact: Susan Tofte 503-494-6445 toftes@ohsu.edu
Principal Investigator: Jon Hanifin, MD

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Food and Drug Administration (FDA)

National Jewish Health

University of California, San Diego

Oregon Health and Science University

Investigators

Study Chair:

Richard Gallo, MD, PhD

University of California, San Diego

More Information

Additional Information:

Click here for more information about the atopic dermatitis vaccine network This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers:	DAIT ADVN CATH 03, Contract No. HHSN266200400029C
Study First Received:	November 11, 2008
Last Updated:	November 24, 2009
ClinicalTrials.gov Identifier:	NCT00789880 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Vitamin D3
Atopic Dermatitis
Antimicrobial Peptide Expression

Additional relevant MeSH terms:

Anti-Infective Agents
Cholecalciferol
Dermatitis, Atopic
Skin Diseases
Immune System Diseases
Growth Substances
Physiological Effects of Drugs
Ergocalciferols
Bone Density Conservation Agents
Pharmacologic Actions

Hypersensitivity
Vitamin D
Genetic Diseases, Inborn
Therapeutic Uses
Vitamins
Hypersensitivity, Immediate
Skin Diseases, Eczematous
Micronutrients
Skin Diseases, Genetic
Dermatitis

ClinicalTrials.gov processed this record on February 08, 2010