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Studies of Skin Microbes in Healthy People and in People With Skin Conditions
This study is currently recruiting participants.
Verified July 2011 by National Institutes of Health Clinical Center (CC)

First Received on January 23, 2008.   Last Updated on December 24, 2011   History of Changes
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:

  • Medical family and medication history
  • Skin examination
  • Blood tests (research blood as well as serum IgE, and complete blood count)
  • Skin samples to analyze microbes. Samples are obtained by the following methods: swabbing the skin with a cotton swab; scraping (scratching) the skin gently with a blade to remove only the outermost skin layers; and, only in adults, biopsy (surgical removal) of a small skin sample less than 1/4-inch (5 mm) in diameter.
  • Nose swabs to analyze microbes.
  • Patients with eczema may have photographs of their skin taken to help monitor the skin rashes.

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
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 390
Study Start Date: January 2008
Detailed Description:

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
Criteria
  • INCLUSION CRITERIA:

Inclusion Criteria for all groups

  1. All subjects: Minimum age of 2 enriches for patients that have active AD and are statistically less likely to resolve during this longitudinal study. Maximum age of 40 is to reduce chance of recruiting patients with age-related changes in skin.
  2. All subjects: Must have a primary care professional who will continue care/evaluation in tandem with the protocol to whom information and recommendations can be communicated.

Inclusion Criteria for Group 1: Healthy Volunteers

  1. Adult males or females WITHOUT asthma or allergic rhinitis aged 18-40.
  2. Subset of males or females 2 - 40 years of age who MAY have asthma or allergic rhinitis, from whom MRSA isolates will be obtained.

Inclusion Criteria for Group 3: Age-Matched Controls

  1. Males or females 2- 18 years of age.
  2. Interval visits and age of controls must match those of enrolled AD patients.

Inclusion Criteria for Groups 2, 4, 5 & 6: AD/HIES/WAS/DOCK8 atients (unless specified otherwise)

  1. AD patients: Diagnosis of atopic dermatitis on the basis of the criteria defined by UK Working Party's Diagnostic Criteria for Atopic Dermatitis. (Reference: Williams HC, Burney PG, Pembroke AC, et al: The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. III. Independent hospital validation. Br J Dermatol 131:406-16, 1994). Included in attachments.
  2. AD patients: SCORAD (SCORing Atopic Dermatitis) score of greater than or equal to 25 indicating AD severity of moderate to severe. Included in appendix. (Reference: Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the Included in attachments.
  3. AD patients: At least one antecubital (or popliteal) fossae must be affected at the time of enrollment to serve as a target site.
  4. HIES, WAS or DOCK8 patients: Must have mutation-proven diagnosis, with or without eczematous dermatitis.

EXCLUSION CRITERIA:

Exclusion Criteria for all groups:

  1. Any subjects with unstable or uncontrolled medical conditions. Individual determinations will be made at the discretion of the medical investigator.
  2. Any subjects receiving or planning to receive an IND agent, ultraviolet light therapy, monoclonal antibodies, or systemic immunosuppressants < 7 days or 5 half-lives (whichever is the longer time period) of initiating this protocol.
  3. Any subjects who have cancer, and are currently or have previously received treatment with chemotherapy or radiation for treatment of malignancies within the previous 6 months.
  4. Any subject with a history of bone marrow transplant or gene therapy.

Exclusion Criteria specific for groups 2, 4, 5 & 6: AD/HIES/WAS/DOCK8 patients (unless specified otherwise):

  1. AD patients: Subjects who are unable to remain off systemic (oral) antibiotics or systemic (oral) steroids for at least 7 days prior to skin sample collection. Subjects who are unable to temporarily discontinue use of topical steroids or calcineurin inhibitors for >= 7 days to small areas of skin intended for sampling. (Topical therapies/emollients for AD may be continued to non-adjacent, non-target sites.)
  2. AD patients: Subjects with underlying immunodeficiency, either as primary disease or secondary to treatment.
  3. WAS/HIES/DOCK8 patients: unable to remain off topical steroids and emollients for preferably 7 days but at least 24 hours prior to skin sampling. HIES/WAS/DOCK8 patients will not be taken off their systemic (oral) antibiotics or systemic (oral) steroids. If unable to withhold topical therapies/emollients, all patients may continue application to non-adjacent, non-target sampling sites.)

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):

  1. Subjects with underlying immunodeficiency, either as primary disease or secondary to treatment.
  2. Subject with other documented chronic dermatologic disease, such as AD or psoriasis, that may interfere with evaluation of the cutaneous microbiome. Common transient conditions, such as acne, are permissible.
  3. Subjects who provide direct healthcare or reside in healthcare facilities or in non-hospital settings such as assisted living facilities, homeless shelters, jails and prisons as well as subjects with frequent exposure to laboratory animals, in order to minimize potential ascertainment bias. (Certain pathogens such as Staphylococcus aureus and multi-drug resistant organisms are disproportionately associated with delivery of healthcare.)
  4. Subjects with asthma or allergic rhinitis, except for the subset of Group 1 healthy volunteers designated as those undergoing sampling for MRSA isolates.
  5. Children with past or ongoing parasitic infection.
  6. Children who immigrated to the U.S. within the last 5 years
  7. Any subject with a chronic disease requiring treatment. Individual determinations will be made at the discretion of the medical investigator.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00605878

Contacts
Contact: Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov
Contact: TTY 1-866-411-1010

Locations
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            
Sponsors and Collaborators
  More Information

Additional Information:
Publications:
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

Keywords provided by National Institutes of Health Clinical Center (CC):
Atopic Dermatitis (Eczema)
Bacteria
Filaggrin
Skin
Microbiome
Atopic Dermatitis
Eczema
Health Volunteer
HG

Additional relevant MeSH terms:
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

ClinicalTrials.gov processed this record on February 09, 2012