Účinky léčby na atopickou dermatitidu
Účinky léčby na mikrobiom u zdravých dobrovolníků a pacientů s atopickou dermatitidou
Background:
- Atopic dermatitis, or eczema, is a chronic skin disorder. Patients sometimes have infections with S. aureus bacteria. Researchers want to study how eczema treatments affect the number and the type of bacteria on the skin.
Objectives:
- To study the effect of eczema treatments on skin bacteria.
Eligibility:
- Individuals between 2 and 25 years of age who have moderate to severe atopic dermatitis.
- Healthy volunteers between 18 and 40 years of age with no history of eczema.
Design:
- Participants will be screened with a physical exam and medical history. Research samples will be collected. Skin biopsies may also be performed.
- All participants will be assigned to one of several study groups.
- Healthy volunteers must not have taken antibiotics in the year before the start of the study.
- All participants will have regular study visits during their 1-year participation. More research samples will be collected at these visits.
- Healthy volunteers may be asked to come in for a one-time follow up after the 1 year mark.
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Detailní popis
BACKGROUND:
- The use of antibiotics has revolutionized medicine, yet the impact of antimicrobials on the human microbiome is incompletely understood.
- Antimicrobial treatments, including topical and systemic antibiotics, are highly effective and are frequently used to manage disease flares of atopic dermatitis (AD). Concomitant use of dilute bleach baths reduces the clinical severity of AD in patients with clinical signs of bacterial skin infections.
- The longitudinal impact of various antimicrobials on the human microbiome, particularly in skin, has not been systematically investigated.
- Our recent study demonstrated that antibiotic-resistant bacteria can be observed after antibiotic exposure; however, multi-year persistence has not been evaluated
OBJECTIVES:
Primary:
- To characterize microbiome alterations in healthy adult volunteers and patients with AD after antimicrobial treatments.
ELIGIBILITY:
- All subjects must be co-enrolled in NIH protocol 08-HG-0059
- (Cohorts 1 [NO FURTHER ACCRUAL], 2 [INACTIVE], 4 [NO FURTHER ACCRUAL], 5 [INACTIVE]) Healthy volunteers aged 18 to 50 years with no history of AD.
- (Cohort 1 [NO FURTHER ACCRUAL], 2 [INACTIVE], 4 [NO FURTHER ACCRUAL] and 5 [INACTIVE]) No prior use of systemic antibiotics in preceding 12 months.
- (Cohort 3 [INACTIVE]) Subjects 2-50 years with atopic dermatitis with symptoms of active bacterial infection.
- (Cohort 3 [INACTIVE]) Objective SCORAD (SCORing Atopic Dermatitis) score of >= 15 indicating moderate-to-severe disease.
- (Cohort 6) Individuals previously enrolled in Cohorts 1 [NO FURTHER ACCRUAL] and 4 [NO FURTHER ACCRUAL].
DESIGN:
- A prospective, interventional, longitudinal study examining changes in microbiome resulting from randomized, placebo-controlled, investigator-blinded antimicrobial treatments.
- Subjects in Cohort 1 [NO FURTHER ACCRUAL] will be randomized to take one of 4 open label antibiotic regimens.
- Subjects from Cohort 2 [INACTIVE] randomized to one of four possible blinded treatment combinations of study baths and antibiotics.
- Subjects in Cohort 3 [INACTIVE] will be randomized to a cephalexin regimen with or without study baths.
- Subjects in Cohorts 4 [NO FURTHER ACCRUAL] and 5 [INACTIVE] will receive one of two open label antibiotic regimens.
- All subjects will undergo longitudinal microbiome sampling.
- Subjects who completed on-protocol antibiotic regimen in Cohorts 1 [NO FURTHER ACCRUAL] and 4 [NO FURTHER ACCRUAL] may be recruited >1 year after completion of Cohorts 1 and 4 to undergo an optional single visit for microbiome sampling as Cohort 6.
- AD patients [INACTIVE] will undergo clinical assessment to determine responses of skin infections to treatment.
Typ studie
Typ studie
Zápis (Odhadovaný)
Zápis
Fáze
Fáze
- Fáze 2
Kontakty a umístění
Studijní kontakt
Studijní kontakt
- Jméno: Heidi H Kong, M.D.
- Telefonní číslo: (301) 827-2460
- E-mail: NIAMSderm@nih.gov
Studijní místa
-
-
Maryland
-
Bethesda, Maryland, Spojené státy, 20892
- Nábor
- National Institutes of Health Clinical Center
-
Kontakt:
- NIH Clinical Center Office of Patient Recruitment (OPR)
- Telefonní číslo: TTY dial 711 800-411-1222
- E-mail: ccopr@nih.gov
-
-
Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
- INCLUSION CRITERIA:
Cohorts 1 [NO FURTHER ACCRUAL], 2 [INACTIVE], 4 [NO FURTHER ACCRUAL] and 5 [INACTIVE]: Healthy Volunteers
- Males and females aged 18-50 years at time of initial protocol sampling
- Subjects must participate fully and be willing to comply with the procedures of the protocol
- Subjects must be co-enrolled in NIH protocol 08-HG-0059
- Ability of subject to understand and provide written informed consent
- Access to bathing facilities (Cohort 2 [INACTIVE])
- Ability to swallow capsules or tablets
Cohort 3 [INACTIVE]: Atopic Dermatitis Patients
- Subjects must be aged 2-50 years
- Subjects must be co-enrolled in NIH protocol 08-HG-0059
- Subjects must have a diagnosis of atopic dermatitis on the basis of the criteria defined by UK Working Party s Diagnostic Criteria for Atopic Dermatitis
- Subjects must have a primary care provider
- Subjects must have an Objective SCORAD (SCORing Atopic Dermatitis) of greater than or equal to 15 indicating AD severity of moderate to severe
- Prior to initiation of randomized treatment, subjects must have signs of bacterial skin infections (skin weeping, crusting, and/or pustules)
- Access to bathing facilities
- All subjects and/or their Legally Authorized Representative (LAR) must have the ability and agree to participate fully and comply with
the procedures of the protocol and provide informed consent. Pediatric patients will be included in age appropriate discussions and
age appropriate assent will be obtained in accordance with NIH guidelines.
-Ability of subject to understand and provide written informed consent
Cohort 6: Healthy Volunteers
- Subjects previously enrolled in Cohorts 1 [NO FURTHER ACCRUAL] and 4 [INACTIVE] who completed on-protocol antibiotic regimen
- Subjects must participate fully and be willing to comply with the procedures of the protocol
- Ability of subject to understand and provide written informed consent
EXCLUSION CRITERIA:
Cohorts 1 [NO FURTHER ACCRUAL] and 2 [INACTIVE]: Healthy Volunteers
- Does not meet inclusion criteria
- Any female with symptoms and/or serum hormone levels consistent with perimenopause or menopause
- Use of systemic antibiotics in 12 months preceding baseline sampling
- Use of swimming pools, hot tubs, or whirlpools in 7 days preceding baseline sampling
- Use of topical or oral complementary/alternative medicine (CAM) agents within 4 weeks of initiation of treatment
- Known allergic reaction to sulfa, beta-lactam, or tetracycline class drugs; or lidocaine or epinephrine
- Family history of toxic epidermal necrolysis
- Known allergy or sensitivity to sodium hypochlorite (NaOCl)
- History of AD or asthma
- Inability to comply with the requirements of the protocol
- Pregnant or lactating
- Subjects with a primary or acquired immunodeficiency, including HIV seropositiviy
- Any chronic past or present medical illness, including chronic skin diseases like psoriasis
- Subjects receiving or planning to receive an IND agent, ultraviolet light therapy, monoclonal antibodies, or systemic immunosuppressants
- 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
Cohort 3 [INACTIVE]: Atopic Dermatitis Patients
- Does not meet inclusion criteria
- Any female with symptoms and/or serum hormone levels consistent with perimenopause or menopause
- Known allergic reaction to beta-lactam class drugs, lidocaine, or epinephrine
- Family history of toxic epidermal necrolysis
- Known allergic reaction to sodium hypochlorite (NaOCl)
- Use of systemic antibiotics within 8 weeks, or topical antibiotics on intended sampling sites within 3 weeks, prior to baseline sampling
- Use of topical corticosteroids on all intended sampling sites within 7 days, prior to baseline sampling
- Use of topical or oral CAM agents within 4 weeks of initiation of treatment
- Subjects with known primary or acquired immunodeficiency
- Subjects with unstable or uncontrolled medical conditions that could require hospitalization during the initial month of the study or who have been hospitalized for treatment of these conditions in the one month prior to baseline sampling
- Subjects receiving or planning to receive an IND agent, ultraviolet light therapy, monoclonal antibodies, or systemic immunosuppressants within 7 days or 5 half-lives (whichever is the longer time period) of initiating treatment on this protocol
- Subjects who are currently receiving or have received chemotherapy or radiation for treatment of malignancies within the previous 6 months
- Pregnancy or lactating
Cohorts 4 [NO FURTHER ACCRUAL] and 5 [INACTIVE]: Healthy Volunteers
- Does not meet inclusion criteria
- Any female with symptoms and/or serum hormone levels consistent with perimenopause or menopause
- Use of systemic antibiotics in 12 months preceding baseline sampling
- Use of swimming pools, hot tubs, or whirlpools in 7 days preceding baseline sampling
- Use of topical or oral complementary/alternative medicine (CAM) agents within 4 weeks of initiation of treatment
- (Cohort 4 [NO FURTHER ACCRUAL]) Known allergic reaction to sulfa class drugs; or lidocaine or epinephrine
- (Cohort 5 [INACTIVE]) Known allergic reaction to tetracycline class drugs; or lidocaine or epinephrine
- Family history of toxic epidermal necrolysis
- History of AD or asthma
- Inability to comply with the requirements of the protocol
- Pregnant or lactating
- Subjects with a primary or acquired immunodeficiency, including HIV seropositivity
- Any chronic past or present medical illness, including chronic skin diseases like psoriasis
- Subjects receiving or planning to receive an IND agent, ultraviolet light therapy, monoclonal antibodies, or systemic immunosuppressants
- 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
Cohort 6: Healthy Volunteers
- Does not meet inclusion criteria
- Use of swimming pools, hot tubs, or whirlpools in 7 days preceding sampling
- Use of topical or oral CAM agents within 1 week or 4 weeks, respectively, prior to sampling
- Pregnant or lactating females in all cohorts are excluded from participating due to the potential effects of the above listed antimicrobials on the developing human fetus or nursing infant; listed in Sections 11.1 through 11.5. Females of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. Lactating mothers will discontinue breastfeeding prior to study enrollment.
- Smokers and subjects who use smokeless tobacco products are excluded in all cohorts due to tobacco s unknown impact on human oral mucosa and microflora.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Singl
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
|---|---|
|
Aktivní komparátor: 1A/Cephalexin
Cephalexin + Placebo bleach |
500 mg orally every 8 hours for 14 days |
|
Aktivní komparátor: 1B/TMP/SMX
TMP/SMZ DS 800 /160 orally every 12 hours for 14 days |
800/160 orally every 12 hours for 14 days |
|
Aktivní komparátor: 1C/Doxycycline 100
Doxycycline 100 mg orally every 12 hours for 56 days |
500 mg orally every 8 hours for 14 days 6 % dilute bleach |
|
Aktivní komparátor: 1D/Doxycycline 20
Doxycycline 20 mg orally every 12 hours for 56 days |
20 mg orally every 12 hours for 56 days or 100 mg orally every 12 hours for 56 days |
|
Aktivní komparátor: 2A/Cephalexin + Dilute bleach
Systemic antibiotics (Cephalexin) + dilute bleach study bath liquid |
500 mg orally every 8 hours for 14 days 6 % dilute bleach |
|
Komparátor placeba: 2B/Cephalexin + Placebo bleach
Systemic antibiotics (Cephalexin) + placebo study bath liquid |
500 mg orally every 8 hours for 14 days Three times a week for 14 days |
|
Komparátor placeba: 2C/Placebo capsules + Dilute bleach
Placebo capsules + dilute bleach study bath liquid |
6 % dilute bleach Capsule orally every 8 hours daily for 14 days |
|
Komparátor placeba: 2D/Placebo capsules + Placebo bleach
Placebo capsules + placebo study bath liquid |
Three times a week for 14 days Capsule orally every 8 hours daily for 14 days |
|
Aktivní komparátor: 3A/Cephalexin + Dilute bleach
Systemic antibiotics (Cephalexin) + dilute bleach study bath liquid |
500 mg orally every 8 hours for 14 days 6 % dilute bleach |
|
Komparátor placeba: 3B/Cephalexin + Placebo bleach
Systemic antibiotics (Cephalexin) + placebo study bath liquid |
500 mg orally every 8 hours for 14 days Three times a week for 14 days |
Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Characterize microbiome alterations
Časové okno: 2 weeks
|
Difference in Shannon Diversity Indices (SDI) from baseline to day 14. |
2 weeks
|
Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
|
Získat vzorky od zdravých dospělých dobrovolníků pro vyhodnocení a zpřesnění genomové analýzy lidských mikrobů.
Časové okno: Po celou dobu studia
|
Po celou dobu studia
|
|
Prozkoumat, jak mohou různé antimikrobiální látky změnit lidský mikrobiom.
Časové okno: Po celou dobu studia
|
Po celou dobu studia
|
Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Heidi H Kong, M.D., National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Publikace a užitečné odkazy
Užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
Primární dokončení (Odhadovaný)
Primární dokončení
Dokončení studie (Odhadovaný)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhadovaný)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Genetické choroby, vrozené
- Onemocnění imunitního systému
- Přecitlivělost, okamžitá
- Přecitlivělost
- Kožní onemocnění, ekzematózní
- Vrozené, dědičné a neonatální nemoci a abnormality
- Onemocnění kůže a pojivové tkáně
- Dermatitida, atopika
- Dermatitida
- Ekzém
- Kožní choroby
- Kožní onemocnění, genetické
- Sloučeniny síry
- Organické chemikálie
- Heterocyklické sloučeniny, 1 kruh
- Heterocyklické sloučeniny
- Heterocyklické sloučeniny, 2-prsten
- Heterocyklické sloučeniny, fúzované kroužek
- Uhlovodíky
- Uhlovodíky, cyklické
- Polycyklické aromatické uhlovodíky
- Uhlovodíky, aromatické
- Polycyklické sloučeniny
- Amidy
- Anilinové sloučeniny
- Aminy
- Anorganické chemikálie
- Sloučeniny chloru
- Pyrimidiny
- Deriváty benzenu
- Nafthacenes
- Oxidy
- Kyslíkové sloučeniny
- Tetracykliny
- Beta-laktamy
- Laktamy
- Cefalosporiny
- Thiaziny
- Benzenesulfonamidy
- Sulfonamidy
- Sulfanilamidy
- Sulfony
- Hypochlozlá kyselina
- Sloučeniny sodíku
- Doxycyklin
- Cephalexin
- Trimethoprim
- Sulfamethoxazol
- Chlornan sodný
Další identifikační čísla studie
Další identifikační čísla studie
- 120159
- 12-AR-0159
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