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Targeted Microbiome Transplant in Atopic Dermatitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03151148
Recruitment Status : Completed
First Posted : May 12, 2017
Last Update Posted : June 21, 2019
Sponsor:
Collaborator:
Atopic Dermatitis Research Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
The purpose of this study is to examine the safety and effectiveness of a new therapy, commensal lotion containing infection fighting bacteria, on decreasing or eliminating the infection causing bacteria found on the skin of Atopic Dermatitis (AD) patients.

Condition or disease Intervention/treatment Phase
Atopic Dermatitis (AD) Biological: TMT Lotion Drug: Placebo Lotion Phase 1 Phase 2

Detailed Description:

This study will enroll adult participants, 18-60 years of age, with moderate-to-severe atopic dermatitis (AD) and a positive Staphylococcus aureus (S. aureus) colonized lesion (at least 15 cm^2 in size) on the upper extremities.

Participants who are eligible based on their positive Staph culture results will be randomized to one of two treatments: Targeted Microbiome Transplant Lotion (TMT) or Placebo (2:1 randomization). One lesional site measuring at least 15 cm^2 and one non-lesional site of equal size will be identified on the participant's ventral upper extremities as the target swabbing areas. These sites will be photographed and marked for swabbing for reference at the participant's future visits. Participants will be instructed to apply investigational product with gloved hands to their ventral upper extremities bilaterally from the wrist to the upper humerus, which will include the identified lesional and non-lesional swabbing sites twice a day for 1 week starting on Day 0. Participants will return to clinic on Day 4 for the assessment of adverse events(s), the collection of skin swabs from the identified target sites, and to obtain additional investigational product and gloves. Participants will complete an additional clinic visit on Day 7 to correspond with the end of their 1 week treatment. During this visit, participants will be assessed for AEs and provide skin swab samples. All unused product and empty packets will be returned during the Day 4 and Day 7 visits. Three additional clinic visits on Days 8, 9, and 11 will be scheduled for additional skin swabs to assess the safety and the stability of the microbiome transplant and time to recurrence of Staph colonization. Participants will be followed through Day 38 to assess for safety and disease status.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A First in Man Evaluation of the Safety and Efficacy of an Allogeneic Targeted Microbiome Transplant in Adults With Moderate-to-Severe Atopic Dermatitis (ADRN-08)
Actual Study Start Date : September 28, 2017
Actual Primary Completion Date : June 7, 2019
Actual Study Completion Date : June 7, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eczema

Arm Intervention/treatment
Experimental: TMT Lotion
The targeted microbiome transplant (TMT) lotion will be provided in single-dose sealed packets. The lotion should be stored at 4°Celsius (=39.2 degrees Fahrenheit). Participants randomized to active TMT will apply 2 grams of TMT to each ventral aspect of their arm (wrist to upper humerus). Frequency of lotion application: topical application administered twice daily for one week.
Biological: TMT Lotion
TMT product and Vegetable glycerin-Cetaphil®
Other Name: Targeted Microbiome Transplant (TMT) Lotion

Placebo Comparator: Placebo Lotion
Placebo lotion will be provided in single-dose sealed packets. The lotion should be stored at 4°Celsius (=39.2 degrees Fahrenheit). Participants randomized to placebo will apply 2 grams of placebo to each ventral aspect of their arm (wrist to upper humerus). Frequency of lotion application: topical application administered twice daily for one week.
Drug: Placebo Lotion
Cetaphil® moisturizing lotion and vegetable glycerin
Other Name: Placebo for Targeted Microbiome Transplant (TMT) Lotion




Primary Outcome Measures :
  1. The Count of Serious and Non-Serious Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Day 0 (after initiation of study treatment) through Day 8 (last day of study treatment) ]
    Unless noted otherwise, severity of adverse events (AEs) and serious adverse events (SAEs) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. All participants who receive study intervention are evaluable for TEAs. This endpoint is measured per participant.


Secondary Outcome Measures :
  1. The Occurrence of at Least One Serious or Non-Serious Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Day 0 (after initiation of study treatment) through Day 8 (last day of study treatment) ]
    Unless noted otherwise, severity of adverse events (AEs) and serious adverse events (SAEs) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. All participants who receive study intervention are evaluable for TEAs. This endpoint is measured per participant.

  2. The Count of Serious and Non-Serious AEs Per Participant During Study Participation [ Time Frame: Day -38 (from initial screening) to Day 38 (last day of study participation) ]
    All observed or volunteered AEs and Serious AEs regardless of treatment group or suspected causal relationship to the investigational product(s). Unless noted otherwise, severity of AEs and SAEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.This endpoint is measured per participant.

  3. The Occurrence of at Least One Serious or Non-Serious Adverse Event (AE) During Study Participation [ Time Frame: Day -38 (from initial screening) to Day 38 (last day of study participation) ]
    All observed or volunteered AEs and Serious AEs regardless of treatment group or suspected causal relationship to the investigational product(s). Unless noted otherwise, severity of AEs and SAEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.This endpoint is measured per participant.

  4. The Eczema Area and Severity Index (EASI) Score of the Ventral Arms at Day 7 After Completion of One Week of Assigned Treatment [ Time Frame: Day 7 (Post Completion of One Week of Randomized Assigned Treatment) ]
    The EASI score of the ventral arms will be assessed at Day 7 post completion of 1 week of assigned treatment. The EASI score is a standardized measure of disease severity, assessing the intensity of four lesion characteristics (erythema, infiltration/population, excoriation, lichenification) each rated on a scale of 0 (absent) to 3 (severe).

  5. The Scoring Atopic Dermatitis (SCORAD) Score at Day 7 After Completion of One Week of Assigned Treatment [ Time Frame: Day 7 (Post Completion of One Week of Randomized Assigned Treatment) ]
    The SCORAD score of the ventral arms will be assessed at Day 7 post completion of 1 week of assigned treatment. The SCORAD is a standardized measure of disease severity.

  6. The Pruritus Visual Analog Scale (VAS) Score of the Ventral Arms at Day 7 After Completion of One Week of Assigned Treatment [ Time Frame: Day 7 (Post Completion of One Week of Randomized Assigned Treatment) ]
    The Pruritus VAS score of the ventral arms will be assessed at Day 7 post completion of 1 week of assigned treatment. The Pruritus VAS is a standardized measure of disease severity.

  7. The Rajka-Langeland (RL) Score at Day 7 After Completion of 1 Week of Assigned Treatment [ Time Frame: Day 7 (Post Completion of One Week of Randomized Assigned Treatment) ]
    The RL of the ventral arms will be assessed at Day 7 post completion of 1 week of assigned treatment. The RL is a standardized measure of disease severity.

  8. The Abundance of Live Coagulase Negative Staphylococcal Species (CoNS) Colony Forming Units (CFU) on Lesional and Non-Lesional Skin at Day 7 After Completion of One Week of Assigned Treatment [ Time Frame: Day 7 (Post Completion of One Week of Randomized Assigned Treatment) ]
    Bacterial abundance of CoNS on lesional and non-lesional skin will be assessed on Day 7 post 1 week of assigned treatment. Unit of measure: CFU/cm^2.

  9. The Time (in Days) to Elimination of Transplanted Coagulase Negative Staphylococcal Species (CoNS) Bacteria on Lesional and Non-Lesional Skin After Completion of 1 Week of Applied Targeted Microbiome Transplant Lotion (TMT) [ Time Frame: After completion of 1 week of Microbiome Transplant (TMT) Lotion Application ]
    Measured by relative colony forming units per centimeter squared (rCFU/cm^2 and CFU/cm^2)

  10. Comparison by Treatment Group of The Abundance of Live Staphylococcus aureus (S. aureus) on Lesional and Non-Lesional Skin at Day 7 after 1 Week of Assigned Treatment [ Time Frame: Day 7 (Post Completion of One Week of Randomized Assigned Treatment) ]
    Measured by colony forming units (CFU)/cm^2.

  11. The Time (In Days) to the First Recurrence of Staphylococcus aureus (S. aureus) Abundance on Lesional and Non-Lesional Skin After Completion of 1 Week of TMT application [ Time Frame: After completion of 1 week of Targeted Microbiome Transplant Lotion (TMT) Lotion Application ]
    Measured by relative colony forming units (rCFU)/cm^2 and CFU/cm^2

  12. The Abundance of Bacterial DNA on Lesional and Non-Lesional Skin at Day 7 after 1 Week of Assigned Treatment [ Time Frame: Day 7 (Post Completion of One week of Randomized Assigned Treatment) ]
    Specific bacteria of interest: Staphylococcus aureus (S. aureus);Staphylococcus hominis (S. hominis); combined Staphylococci; and combined bacteria Measured by relative colony forming units (rCFU)/cm^2.


Other Outcome Measures:
  1. EXPLORATORY: The proportion (Percent Relative Abundance) by Phylum: Class and Shannon Diversity Index of the Microbiome on Lesional and Non-Lesional Skin at Day 7 After Completion of 1 Week of Assigned Treatment [ Time Frame: Day 7 (Post Completion of 1 Week of Randomized Assigned Treatment) ]
    To identify the diversity of the lesional and non-lesional skin microbiome by DNA sequencing after completion of 1 week of assigned treatment.

  2. EXPLORATORY:Transcription Profiles of the Microbiome on Lesional and Non-Lesional Skin [ Time Frame: Day 7 (Post Completion of One Week of Randomized Assigned Treatment) ]
    To evaluate the lesional and non-lesional skin microbiome transcriptome by ribonucleic acid (RNA) sequencing after completion of 1 week of assigned treatment.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Individuals who meet all of the following criteria are eligible for enrollment as study participants:

  • Participant must be able to understand and provide informed consent;
  • Fulfills the Atopic Dermatitis Research Network (ADRN) Standard Diagnostic Criteria (Appendix A) for active Atopic Dermatitis (AD);
  • A Staphylococcus aureus (S. aureus) positive culture colonized lesion, at least 15 cm^2 in size, located on a ventral upper extremity (e.g., arm);
  • An Investigator Global Assessment (IGA) score, on the ventral arms, of at least moderate severity;
  • A body surface area (BSA), as measured by Mosteller BSA Calculator, between 1.26 m^2 (e.g., 4 feet, 10 inches and 85 pounds [38.6 Kg])and 2.25 m^2 (e.g., 6 feet, 3 inches and 210 pounds [95.5 Kg]); and
  • Females of childbearing potential who are willing to use adequate contraception 30 days prior to the Screening Visit and until participation in the study is complete.

    --Females of childbearing potential must agree to use an acceptable method of birth control (e.g. total abstinence, oral contraceptives, intrauterine device (IUD), barrier method with spermicide, surgical sterilization or surgically sterilized partner, Depo-Provera, Norplant, NuvaRing, or hormonal implants) for the duration of study participation.

  • Male participants who are willing to use an acceptable method of contraception (e.g. barrier methods with spermicide, surgical sterilization or surgically sterilized partner) or practice abstinence until participation in the study is complete.

Exclusion Criteria:

  • Inability or unwillingness of participant to give written informed consent or comply with study protocol;
  • Pregnant or lactating females, or females who desire to become pregnant and/or breast feed within the duration of study participation;
  • Active bacterial, viral, or fungal skin infections;
  • Any noticeable breaks or cracks in the skin on the upper extremities, including severely excoriated skin or skin with open or weeping wounds suggestive of an active infection or increased susceptibility to infection;
  • Sensitivity to or difficulty tolerating Dove fragrance-free bar soap, Cetaphil(R) Lotion, alcohol-based cleaners, , macadamia nuts, soy, Vegetable glycerin, or palm kernels;
  • Participants with prosthetic heart valves, pacemakers, intravascular catheters, or other foreign or prosthetic devices;
  • Participants with Netherton's syndrome or other genodermatoses that result in a defective epidermal barrier;
  • Any participant who is immunocompromised (e.g. history of lymphoma, Human Immunodeficiency Virus (HIV)/ Acquired Immune Deficiency Syndrome (AIDS), Wiskott-Aldrich Syndrome) or has a history of malignant disease (with the exception of non-melanoma skin cancer);
  • Participants with a history of psychiatric disease or history of alcohol or drug abuse that would interfere with the ability to comply with the study protocol;
  • Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study;
  • Ongoing participation in another investigational trial or use of investigational drugs within 8 weeks, or 5 half-lives (if known), whichever is longer, of the Screening Visit;
  • Treatment with biologics within 16 weeks of Screening Visit;
  • Participants with close contacts (e.g. spouses, children, or members in the same household) that have severe barrier defects or are immunocompromised;
  • Use of topical (including steroids and calcineurin inhibitors) Atopic Dermatitis (AD) treatments within 7 days of the Treatment Visit; Use of topical steroids on areas outside of where investigational product is to be applied may be permitted, per investigator discretion;
  • Treatment of AD with prescription moisturizers classified as medical device (e.g., Atopiclair(®, MimyX®, Epicerum®, Cerave®, etc.) within 7 days of the Treatment Visit;
  • Use of any oral or topical antibiotics within 7 days of the Treatment Visit;
  • Participants who have taken a bleach bath within 7 days of the Treatment Visit;
  • Use of any oral AD therapies (antihistamines, steroids, immunosuppressive therapies) within 28 days of the Treatment Visit; or
  • Any phototherapy for skin disease (such as narrow band ultraviolet B [NBUVB], ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + UVA [PUVA]) or regular use (more than 2 visits per week) of a tanning bed within 28 days of the Treatment Visit.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03151148


Locations
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United States, California
University of California - San Diego
San Diego, California, United States, 92122
United States, Colorado
National Jewish Health General Clinical Research Center
Denver, Colorado, United States, 80206
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Atopic Dermatitis Research Network
Investigators
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Study Chair: Richard Gallo, M.D., Ph.D. University of California, San Diego: Dermatology Clinical Trials Unit

Additional Information:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03151148     History of Changes
Other Study ID Numbers: DAIT ADRN-08
First Posted: May 12, 2017    Key Record Dates
Last Update Posted: June 21, 2019
Last Verified: June 2019

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

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
allogeneic targeted microbiome transplant (TMT)
dysbiosis in AD
Staphylococcus aureus colonized skin
antimicrobial peptides (AMPs)
randomized trial

Additional relevant MeSH terms:
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Dermatitis
Dermatitis, Atopic
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases