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

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
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

MedlinePlus related topics: Smallpox

Drug Information available for: Vitamin D Ergocalciferol Cholecalciferol

U.S. FDA Resources

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

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:	September 2009
Estimated Primary Completion Date:	September 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:

People of any race or ethnicity who meet all of the following criteria are eligible for enrollment into the study:
1. The subject:
  1. has a definitive diagnosis of AD for at least 6 months, stringently diagnosed using the ADVN Standard Diagnostic Criteria, and has lesional skin present; or
  2. is a non-atopic healthy control subject with no personal or family history of food allergy, AD, asthma, or allergic rhinitis.
2. Persons residing in the US.
3. Subjects 18 to 70 years of age.

Exclusion Criteria:

People who meet any of the following criteria are disqualified from enrollment in the study:
1. Under 18 or over 70 years of age.
2. Presence of atopy without stringent AD features, allowing only a presumptive diagnosis of AD.
3. Presence of AD with exfoliative erythroderma.
4. Presence of psoriasis
5. Pregnant or lactating females.
6. Existence of ongoing dental disease (e.g., gingivitis).
7. History of bleeding disorders.
8. Presence of AD that would be exacerbated by withholding of topical corticosteroids, oral or topical antibiotics, antihistamines, oral antivirals, immune enhancers (e.g., imiquod), or topical calcineurin inhibitors within 7 days of recruitment and throughout the course of the trial.
9. Receiving systemic immunosuppressives, chemotherapeutic agents, anti-inflammatory biologics (e.g., alefacept, etanercept), or oral calcineurin inhibitors 30 days prior to the Study Visit 1 (Screening) or anytime during the course of the trial.
10. Using topical corticosteroids, oral or topical antibiotics, oral antivirals, immune enhancers (e.g., imiquimod), vitamin D supplements, or topical calcineurin inhibitors within 7 days of recruitment and during the course of the trial.
11. Receiving phototherapy (e.g., UVB, psoralen plus ultraviolet light A [PUVA]) within 30 days of recruitment.
12. Having autoimmune or immunodeficiency disease.
13. Presence of active systemic fungal, bacterial, or viral infections.
14. Presence of active systemic malignancy, excluding uncomplicated non-melanoma skin cancer.
15. 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.
16. Inability or unwillingness of a participant to give written informed consent.
17. Diabetes.
18. Subjects with screening laboratory values not within normal limits, which would include calcium, 25-hydroxy vitamin D, and serum creatinine.
19. History of kidney disease or kidney stones.
20. Patients taking barbiturates such as pheonobarbital (Luminal).
21. Subjects taking carbamazine (Tegretol), digoxin, phenytoin (Dilantin) or forphenytoin (cerebyx).
22. Patients on diuretics such as thiazide diuretics, calcium channel blockers, or beta-blockers
23. Patients taking magnesium-containing antacids, mineral oil, cholestyramine (Questran), colestipol(Colestid), oristat (xenical), or that fat substitute Olestra
24. Oral antifungals such as ketoconazole.
25. Patients with a history of serious or life-threatening anaphylactic reaction to tape or adhesives.
26. Patients with lidocaine allergy.
27. Subjects with a 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
San Diego, California, United States
United States, Colorado
National Jewish Health
Denver, Colorado, United States
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States

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

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

Responsible Party:	DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers:	ADVN CATH 03, Contract No. HHSN266200400029C
Study First Received:	November 11, 2008
Last Updated:	November 14, 2008
ClinicalTrials.gov Identifier:	NCT00789880
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

Study placed in the following topic categories:

Cholecalciferol
Hypersensitivity
Vitamin D
Dermatitis, Atopic
Genetic Diseases, Inborn
Skin Diseases

Ergocalciferols
Hypersensitivity, Immediate
Skin Diseases, Eczematous
Skin Diseases, Genetic
Dermatitis

Additional relevant MeSH terms:

Immune System Diseases
Growth Substances
Vitamins
Physiological Effects of Drugs

Bone Density Conservation Agents
Micronutrients
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009