Effects of Treatments on Atopic Dermatitis

• ClinicalTrials.gov Identifier: NCT01631617
• Recruitment Status: Recruiting
• First Posted: June 29, 2012
• Last Update Posted: May 25, 2022
• Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) )

Study Description

Brief Summary:

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.
• This study will last for up to 1 year. 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.

Condition or disease	Intervention/treatment	Phase
Eczema; Dermatitis; Skin Diseases, Genetic; Dermatitis, Atopic; Skin Diseases	Drug: Trimethoprim/sulfamethoxazole (TMP/SMZ); Drug: Cephalexin; Drug: Doxycycline; Other: Sodium hypochlorite; Other: Placebo capsules; Other: Placebo Sodium hypochlorite	Phase 2

Detailed 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 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.

OBJECTIVES:

Primary:

-To characterize microbiome alterations in healthy adult volunteers (Cohorts 1 and 2) and patients with AD (Cohort 3) after antimicrobial treatments.

ELIGIBILITY:

• All subjects must be co-enrolled in NIH protocol 08-HG-0059
• (Cohorts 1 and 2) Healthy volunteers aged 18 to 50 years with no history of AD
• (Cohort 1 and 2) No prior use of systemic antibiotics in preceding 12 months
• (Cohort 3) Subjects 2-50 years with atopic dermatitis with symptoms of active bacterial infection
• (Cohort 3) Objective SCORAD (SCORing Atopic Dermatitis) score of greater than or equal to 15 indicating moderate-to-severe disease

DESIGN:

• A prospective, interventional, longitudinal study examining changes in microbiome resulting from randomized, placebo-controlled, investigator-blinded antimicrobial treatments.
• Subjects in Cohort 1 will be randomized to take one of 4 open label antibiotic regimens.
• Subjects from Cohort 2 will be will be randomized to one of four possible blinded treatment combinations of study baths and antibiotics.
• Subjects in Cohort 3 will be randomized to a cephalexin regimen with or without study baths.
• All subjects will undergo longitudinal microbiome sampling.
• AD patients will undergo clinical assessment to determine responses of skin infections to treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Effects of Treatments on the Microbiome in Healthy Volunteers and Patients With Atopic Dermatitis
• Actual Study Start Date: September 18, 2012
• Estimated Primary Completion Date: January 1, 2024
• Estimated Study Completion Date: January 1, 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1A/Cephalexin; Cephalexin + Placebo bleach	Drug: Cephalexin; 500 mg orally every 8 hours for 14 days
Active Comparator: 1B/TMP/SMX; TMP/SMZ DS 800 /160 orally every 12 hours for 14 days	Drug: Trimethoprim/sulfamethoxazole (TMP/SMZ); 800/160 orally every 12 hours for 14 days
Active Comparator: 1C/Doxycycline 100; Doxycycline 100 mg orally every 12 hours for 56 days	Drug: Cephalexin; 500 mg orally every 8 hours for 14 days; Other: Sodium hypochlorite; 6 % dilute bleach
Active Comparator: 1D/Doxycycline 20; Doxycycline 20 mg orally every 12 hours for 56 days	Drug: Doxycycline; 20 mg orally every 12 hours for 56 days or 100 mg orally every 12 hours for 56 days
Active Comparator: 2A/Cephalexin + Dilute bleach; Systemic antibiotics (Cephalexin) + dilute bleach study bath liquid	Drug: Cephalexin; 500 mg orally every 8 hours for 14 days; Other: Sodium hypochlorite; 6 % dilute bleach
Placebo Comparator: 2B/Cephalexin + Placebo bleach; Systemic antibiotics (Cephalexin) + placebo study bath liquid	Drug: Cephalexin; 500 mg orally every 8 hours for 14 days; Other: Placebo Sodium hypochlorite; Three times a week for 14 days
Placebo Comparator: 2C/Placebo capsules + Dilute bleach; Placebo capsules + dilute bleach study bath liquid	Other: Sodium hypochlorite; 6 % dilute bleach; Other: Placebo capsules; Capsule orally every 8 hours daily for 14 days
Placebo Comparator: 2D/Placebo capsules + Placebo bleach; Placebo capsules + placebo study bath liquid	Other: Placebo capsules; Capsule orally every 8 hours daily for 14 days; Other: Placebo Sodium hypochlorite; Three times a week for 14 days
Active Comparator: 3A/Cephalexin + Dilute bleach; Systemic antibiotics (Cephalexin) + dilute bleach study bath liquid	Drug: Cephalexin; 500 mg orally every 8 hours for 14 days; Other: Sodium hypochlorite; 6 % dilute bleach
Placebo Comparator: 3B/Cephalexin + Placebo bleach; Systemic antibiotics (Cephalexin) + placebo study bath liquid	Drug: Cephalexin; 500 mg orally every 8 hours for 14 days; Other: Placebo Sodium hypochlorite; Three times a week for 14 days

Outcome Measures

Primary Outcome Measures :

1. Characterize microbiome alterations [ Time Frame: 2 weeks ]
   Difference in Shannon Diversity Indices (SDI) from baseline to day 14.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 50 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

• INCLUSION CRITERIA:

Cohorts 1 and 2: Healthy Volunteers

Males and females aged 18-50 years.

• 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
• Ability to swallow capsules or tablets

Cohort 3: 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.

EXCLUSION CRITERIA:

Cohorts 1 and 2: Healthy Volunteers

• Does not meet inclusion criteria
• Any female with symptoms and/or serum hormone levels consistent with perimenopause
• 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 and 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 clinics, assisted living facilities, homeless shelters, jails and prisons as well as subjects with frequent exposure to laboratory animals

Cohort 3: Atopic Dermatitis Patients

• Does not meet inclusion criteria
• Any female with symptoms and/or serum hormone levels consistent with perimenopause
• 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
• 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.

Contacts and Locations

Contacts

Contact: Glenna Banania; (301) 402-6225; glenna.banania@nih.gov

Contact: Heidi H Kong, M.D.; (301) 827-2460; konghe@mail.nih.gov

Locations

United States, Maryland

National Institutes of Health Clinical Center; Recruiting

Bethesda, Maryland, United States, 20892

Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 prpl@cc.nih.gov

Sponsors and Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

• Principal Investigator: Heidi H Kong, M.D.; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

• Responsible Party: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• ClinicalTrials.gov Identifier: NCT01631617
• Other Study ID Numbers: 120159; 12-AR-0159
• First Posted: June 29, 2012
• Last Update Posted: May 25, 2022
• Last Verified: September 10, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) ):

Investigator-Blinded; Skin Biopsy; Randomized; Antibiotics; Topical

Additional relevant MeSH terms:

Dermatitis, Atopic; Genetic Diseases, Inborn; Skin Diseases, Genetic; Dermatitis; Skin Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Doxycycline; Cephalexin; Trimethoprim; Sulfamethoxazole; Sodium Hypochlorite; Eusol; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents, Urinary; Renal Agents; Folic Acid Antagonists; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Dyskinesia Agents; Cytochrome P-450 CYP2C8 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Disinfectants