Effects of Treatments on Atopic Dermatitis

National Institutes of Health (NIH)

Status and phase: Enrolling; Phase 2

Conditions: Dermatitis, Atopic; Dermatitis; Skin Diseases; Eczema; Skin Diseases, Genetic

Treatments: Drug: Doxycycline; Other: Sodium hypochlorite; Other: Placebo Sodium hypochlorite; Drug: Trimethoprim/sulfamethoxazole (TMP/SMZ); Other: Placebo capsules; Drug: Cephalexin

Study type: Interventional

Funder types: NIH

Identifiers

NCT01631617

120159

12-AR-0159

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 130 estimated patients

Sex: All

Ages: 2 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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130 participants in 10 patient groups, including a placebo group

1A/Cephalexin

Active Comparator group

Description:

Cephalexin + Placebo bleach

Treatment:

Drug: Cephalexin

1B/TMP/SMX

Active Comparator group

Description:

TMP/SMZ DS 800 /160 orally every 12 hours for 14 days

Treatment:

Drug: Trimethoprim/sulfamethoxazole (TMP/SMZ)

1C/Doxycycline 100

Active Comparator group

Description:

Doxycycline 100 mg orally every 12 hours for 56 days

Treatment:

Drug: Cephalexin

Other: Sodium hypochlorite

1D/Doxycycline 20

Active Comparator group

Description:

Doxycycline 20 mg orally every 12 hours for 56 days

Treatment:

Drug: Doxycycline

2A/Cephalexin + Dilute bleach

Active Comparator group

Description:

Systemic antibiotics (Cephalexin) + dilute bleach study bath liquid

Treatment:

Drug: Cephalexin

Other: Sodium hypochlorite

2B/Cephalexin + Placebo bleach

Placebo Comparator group

Description:

Systemic antibiotics (Cephalexin) + placebo study bath liquid

Treatment:

Drug: Cephalexin

Other: Placebo Sodium hypochlorite

2C/Placebo capsules + Dilute bleach

Placebo Comparator group

Description:

Placebo capsules + dilute bleach study bath liquid

Treatment:

Other: Placebo capsules

Other: Sodium hypochlorite

2D/Placebo capsules + Placebo bleach

Placebo Comparator group

Description:

Placebo capsules + placebo study bath liquid

Treatment:

Other: Placebo capsules

Other: Placebo Sodium hypochlorite

3A/Cephalexin + Dilute bleach

Active Comparator group

Description:

Systemic antibiotics (Cephalexin) + dilute bleach study bath liquid

Treatment:

Drug: Cephalexin

Other: Sodium hypochlorite

3B/Cephalexin + Placebo bleach

Placebo Comparator group

Description:

Systemic antibiotics (Cephalexin) + placebo study bath liquid

Treatment:

Drug: Cephalexin

Other: Placebo Sodium hypochlorite