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| Sponsor: | National Human Genome Research Institute (NHGRI) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00605878 |
Purpose
This study will examine microbes (e.g., bacteria, fungi, viruses) that live on human skin and how microbes contribute to health and disease. It will analyze healthy human skin and how the these microorganisms might change in patients with atopic dermatitis (AD), a skin condition also known as eczema.
Healthy volunteers, as well as patients with moderate to severe eczema (AD), between 2 and 40 years of age may be eligible for this study.
We also wish to enroll children and adults aged 2-40 who have been diagnosed with inherited immune disorders known as HIES (hyperimmunoglobulin-E syndrome), WAS (Wiskott-Aldrich syndrome), or DOCK8 immunodeficiency because they frequently have skin problems similar to AD.
Eligible participants undergo the following tests and procedures:
Participants may be contacted periodically for follow-up studies. Patients with atopic dermatitis may have additional skin samples collected to examine changes in the skin bacteria over time and during all of the stages of eczema. In addition, patients who have a flare of their eczema are asked to undergo a skin sample collection as soon as possible.
| Condition |
|---|
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Atopic Dermatitis Eczema Ichthyosis Vulgaris |
| Study Type: | Observational |
| Study Design: | Time Perspective: Prospective |
| Official Title: | Studies of Skin Microflora in Healthy Individuals and Atopic Dermatitis Patients |
| Estimated Enrollment: | 390 |
| Study Start Date: | January 2008 |
We hypothesize that skin microflora (bacteria, fungi, viruses, phage, archae) plays a significant role in common dermatological conditions, such as atopic dermatitis (a common form of eczema). There are two classical explanations for the role microbes play in skin disease: (1) a specific microbe colonizes the skin to disrupt the balance of commensal microflora, or (2) microbes release toxic substances or invade cells to induce an inflammatory response directly. Since culture-dependent skin sampling methods are incomplete and often biased assessments of microbial diversity, we propose to use genomic methods to sample skin microflora and shed light on the above conjectures. A cultivation-independent genomic approach directly sequences the microbial DNA, enabling us to determine microbial community membership, structure and diversity. Our initial study of skin bacteria analyzed the bacterial 16s rRNA gene, which contains highly conserved regions, allowing for amplification with specific primers, that flank highly variable regions. These sequences suggest the identity of the species being sampled and enable us to infer phylogenetic relationships.
Atopic dermatitis (AD, eczema ) is a prevalent chronic disorder that affects ~15% of the population with an age of onset in the first year of life. AD is characterized by barrier-impaired, dry, itchy skin with immune cell infiltration. $1 billion is spent annually in the USA on treatment and associated costs of AD.1 Studies have identified the first human genetic alteration that is strongly associated with AD as null mutations in the filaggrin (FLG) gene, which encodes an epidermal structural protein.2 These FLG mutations are associated with AD in a semi-dominant fashion and are present in ~47% of European Caucasians with AD. We developed a filaggrin-deficient animal model that shows a selective shift in the microbial community structure, integrating the gene-environment interaction of the host and the microflora.
Chronic eczema is also typical of three rare primary immunodeficiencies: Wiskott-Aldrich syndrome (WAS) (OMIM 301000), which is also characterized by impaired cellular and humoral immunity, thrombocytopenia, and increased frequency of infections; and hyper-IgE syndrome (HIES) (OMIM 147060) which is also characterized, recurrent infections, and increased serum IgE; Combined immunodeficiency associated with DOCK8 mutation syndrome (OMIM 243700), a newly defined immunodeficiency followed at the NIH3-4 which is characterized by recurrent sinopulmonary infections as well as severe cutaneous viral infections. WAS, HIES and DOCK8 immunodeficiencies are caused by mutations in the WASp, STAT3 genes and DOCK8 genes, respectively.
These studies will investigate changes in microbial diversity associated with AD, WAS, HIES, and DOCK8 mutations in pediatric and adult populations to structure future experiments on how to medically manage AD. We will also explore if the progression of eczema is correlated with a selective shift in the skin microbiome specific to the underlying genetic etiology.
Eligibility| Ages Eligible for Study: | 2 Years to 40 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria for all groups
Inclusion Criteria for Group 1: Healthy Volunteers
Inclusion Criteria for Group 3: Age-Matched Controls
Inclusion Criteria for Groups 2, 4, 5 & 6: AD/HIES/WAS/DOCK8 atients (unless specified otherwise)
EXCLUSION CRITERIA:
Exclusion Criteria for all groups:
Exclusion Criteria specific for groups 2, 4, 5 & 6: AD/HIES/WAS/DOCK8 patients (unless specified otherwise):
Exclusion Criteria specific for Groups 1 & 3: Healthy Volunteers and Age-Matched Controls (In addition to the general exclusion criteria listed above for all groups unless specified otherwise):
Contacts and Locations| Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
| Contact: TTY | 1-866-411-1010 |
| United States, Maryland | |
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
| Sub-Investigator: Patient Recruitment and Public Liaison Office (PRPL) For more information at the NIH Clinical Center contact | |
More Information
| ClinicalTrials.gov Identifier: | NCT00605878 History of Changes |
| Other Study ID Numbers: | 080059, 08-HG-0059 |
| Study First Received: | January 23, 2008 |
| Last Updated: | December 24, 2011 |
| Health Authority: | United States: Federal Government |
|
Atopic Dermatitis (Eczema) Bacteria Filaggrin Skin Microbiome |
Atopic Dermatitis Eczema Health Volunteer HG |
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Dermatitis Dermatitis, Atopic Eczema Ichthyosis Ichthyosis Vulgaris Skin Diseases Skin Diseases, Genetic Genetic Diseases, Inborn |
Skin Diseases, Eczematous Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Skin Abnormalities Congenital Abnormalities Infant, Newborn, Diseases Keratosis |