| City: |
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Bethesda |
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State:
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MD |
| Zip Code: |
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20892 |
| Conditions: |
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Atopic Dermatitis - Eczema - Ichthyosis Vulgaris |
| Purpose: |
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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.
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| Study summary: |
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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. |
| Criteria: |
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- 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 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.
2. AD patients: SCORAD (SCORing Atopic Dermatitis) score of greater than or equal to 25
indicating AD severity of moderate to severe.
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 that could require
hospitalization during the course of the study or who have been hospitalized in the
last month.
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 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 chronic disease requiring treatment; e.g. diabetes, bone marrow
transplant, hepatitis.
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 greater than or equal to 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 may be continued to
non-adjacent, non-target 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 cutaneous microbiome. Common transient
conditions, such as acne, are permissible.
3. Subjects who work or reside in healthcare facilities or in non-hospital settings that
provide healthcare 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.
Children who immigrated to the U.S. within the last 5 years. |
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| Study is available at: |
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National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, MD 20892
United States
Primary Contact:
Patient Recruitment and Public Liaison Office
Email: prpl@mail.cc.nih.gov
Phone: (800) 411-1222 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 22, 2011 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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