<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03018275</url>
  </required_header>
  <id_info>
    <org_study_id>170033</org_study_id>
    <secondary_id>17-I-0033</secondary_id>
    <nct_id>NCT03018275</nct_id>
  </id_info>
  <brief_title>Beginning Assessment of Cutaneous Treatment Efficacy of Roseomonas in Atopic Dermatitis</brief_title>
  <official_title>Beginning Assessment of Cutaneous Treatment Efficacy of Roseomonas in Atopic Dermatitis Phase I/II</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Atopic dermatitis (AD) is a skin disease also called eczema. It is common in children and&#xD;
      sometimes gets better on its own. However, chronic AD may cause asthma, food allergies, eye&#xD;
      infections, and sleep problems. The cause of AD might be related to bacteria that live on the&#xD;
      skin. Researchers want to see if introducing bacteria, R mucosa, from healthy skin onto the&#xD;
      skin of someone with AD helps treat the disease.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To test the safety and activity of R mucosa for treating AD.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Part 1: People ages 18 and older with AD&#xD;
&#xD;
      Part 2: Children ages 3-17 with AD&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened with:&#xD;
&#xD;
      Medical history&#xD;
&#xD;
      Physical exam&#xD;
&#xD;
      Examination of their AD&#xD;
&#xD;
      Blood and urine tests&#xD;
&#xD;
      At the baseline visit, participants will have blood tests and photos taken of their skin.&#xD;
      They will get a supply of R mucosa and a memory aid to track their doses and record how they&#xD;
      are feeling. Part 2 participants guardians will complete questionnaires about their child s&#xD;
      AD.&#xD;
&#xD;
      Part 1 participants will spray R mucosa on their arm twice per week for 6 weeks.&#xD;
&#xD;
      Part 2 guardians will spray it on their child s arm twice per week for 16 weeks.&#xD;
&#xD;
      Participants will have follow-up visits to repeat some baseline tests and review their memory&#xD;
      aid:&#xD;
&#xD;
      Part 1: Six weeks after the baseline visit&#xD;
&#xD;
      Part 2: Four times over 16 weeks; then 2 or 3 times for 1 year&#xD;
&#xD;
      Participants will be called or emailed to discuss how they are feeling:&#xD;
&#xD;
      Part 1: About 30 days after their last visit&#xD;
&#xD;
      Part 2: About every 10 days between visits&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The underlying pathology of atopic dermatitis (AD) consists of defective skin barrier&#xD;
      function, susceptibility to Staphylococcus aureus skin infection, and immune imbalance. There&#xD;
      is currently no cure for AD. Preclinical data in a mouse model of AD suggest that commensal&#xD;
      Gram-negative bacteria (CGN), such as Roseomonas mucosa, from a healthy source can relieve&#xD;
      symptoms of AD and have antimicrobial effects. In this study, we will first evaluate the&#xD;
      safety of R mucosa-based biotherapy in adults with AD (age 18+ years; part 1), and then&#xD;
      evaluate the safety and activity of R mucosa-based biotherapy in children (ages 3-17 years)&#xD;
      with AD (parts 2A and 2B). In part 1, participants will receive twice-weekly doses of CGN&#xD;
      biotherapy for 6 weeks, with dose escalations at 2 and 4 weeks. In part 2, participants will&#xD;
      receive twice-weekly doses of CGN biotherapy for 4 months, with possible dose escalations at&#xD;
      4 and 8 weeks (part 2A only). Starting at 12 weeks for both parts 2A and 2B, dosing frequency&#xD;
      may be increased to every other day. Participants in part 1 will be contacted 30 10 days&#xD;
      after end of treatment for assessment of safety. Participants in parts 2A and 2B will also be&#xD;
      followed for up to 1 year after the end of treatment for evaluation of long-term activity and&#xD;
      safety. This will be the first study to test cutaneous live biotherapeutic products for AD.&#xD;
      We hypothesize that altering the strains of CGN on the skin of people with AD will improve&#xD;
      the patient s clinical outcome. We do not expect serious toxicities because R mucosa is&#xD;
      rarely pathogenic; reported cases of bacteremia have typically been associated with&#xD;
      percutaneous catheters in immunocompromised patients, who are excluded from this study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 20, 2017</start_date>
  <completion_date type="Actual">October 11, 2019</completion_date>
  <primary_completion_date type="Actual">October 11, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>A 50% reduction in antecubital-specific SCORing Atopic Dermatitis (SCORAD) with no adverse events related to product use. Frequency of solicited adverse events, unsolicited adverse events, serious adverse events, and death.</measure>
    <time_frame>4 weeks, 8 weeks, 12 weeks, 16 weeks, 8 months, 12 months, and 16 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>A 30% improvement in the quality of life as measured by the validated Children's Dermatology Life Quality Index (CDLQI)</measure>
    <time_frame>4 weeks, 8 weeks, 12 weeks, 16 weeks, 8 months, 12 months, and 16 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A 30% improvement in the quality of life as measured by the validated Family Dermatology Life Quality Index (FDLQI)</measure>
    <time_frame>4 weeks, 8 weeks, 12 weeks, 16 weeks, 8 months, 12 months, and 16 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Atopic Dermatitis</condition>
  <arm_group>
    <arm_group_label>1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vials of lyophilized R mucosa (10&quot;3, 10&quot;4, or 10&quot;5 CFU)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Roseomonas mucosa</intervention_name>
    <description>R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.</description>
    <arm_group_label>1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
        Inclusion Criteria for Young Adults and Adults with AD (Part 1)&#xD;
&#xD;
          1. Age 16+ years&#xD;
&#xD;
          2. SCORAD of at least 10&#xD;
&#xD;
          3. Have a clinical diagnosis of AD with active involvement of the antecubital fossa&#xD;
&#xD;
          4. Willing to allow storage of blood for future research&#xD;
&#xD;
          5. No history of other skin disease&#xD;
&#xD;
          6. Initiated or attempted standard of care therapy at least 6 months prior to enrollment&#xD;
&#xD;
          7. Must agree to use adequate contraception (hormonal or barrier method of birth control&#xD;
             or abstinence) when engaging in sexual activities that can result in pregnancy. The&#xD;
             effects of CGN live biotherapy on the developing human fetus are unknown. Adequate&#xD;
             contraception must be used consistently, beginning before the first dose and lasting&#xD;
             for the duration of study participation. Participants of childbearing potential must&#xD;
             have a negative pregnancy test result before they receive CGN live biotherapy. During&#xD;
             the course of the study, if a participant becomes pregnant or suspects they are&#xD;
             pregnant, then they should inform the study staff and their primary care physician&#xD;
             immediately.&#xD;
&#xD;
        Inclusion Criteria for Children with AD (Part 2)&#xD;
&#xD;
          1. Age 3-16 years&#xD;
&#xD;
          2. SCORAD of at least 10&#xD;
&#xD;
          3. Have a clinical diagnosis of AD with active involvement of the antecubital fossa&#xD;
&#xD;
          4. Willing to allow storage of blood and bacterial swabs for future research&#xD;
&#xD;
          5. Initiated or attempted standard of care therapy at least 6 months prior to enrollment&#xD;
&#xD;
          6. Participants who have begun menstruating must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control or abstinence) when engaging in sexual&#xD;
             activities that can result in pregnancy.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          1. Presence of an indwelling venous or arterial catheter&#xD;
&#xD;
          2. Individuals living with anyone with a diagnosed immunodeficiency, cardiac valvular&#xD;
             disease, and/of indwelling catheter&#xD;
&#xD;
          3. Precence of allergies to aimkacin, ciprofloxacin, gentamicin, levofloxacin, and&#xD;
             tobramycin (which would preclude treatment of any unexpected infection)&#xD;
&#xD;
          4. History of cardiac valvular disease&#xD;
&#xD;
          5. Any history of grade 2 or higher neutropenia or leukopenia&#xD;
&#xD;
          6. Clinical suspicion of immunodeficiency, liver disorder, kidney disorder, and/or HIV&#xD;
&#xD;
          7. Pregnant or breastfeeding&#xD;
&#xD;
          8. Any history of anti-TNF treatment&#xD;
&#xD;
          9. Inability to demonstrate proper bacteria administration procedure despite coaching and&#xD;
             training&#xD;
&#xD;
         10. Use of fluoroquinolone or aminoglycoside antibiotics within 2 weeks of enrollment&#xD;
&#xD;
         11. Any condition that, in the opinion of the investigator, contraindicates participation&#xD;
             in this Study&#xD;
&#xD;
        Co-enrollment guidelines: Co-enrollment in other trials is restricted, other than&#xD;
        enrollment on observational studies or those evaluating the use of a licensed medication.&#xD;
        Study staff should be notified of co-enrollment as it may require the approval of the&#xD;
        investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ian A Myles, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Allergy and Infectious Diseases (NIAID)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Boguniewicz M, Leung DY. Recent insights into atopic dermatitis and implications for management of infectious complications. J Allergy Clin Immunol. 2010 Jan;125(1):4-13; quiz 14-5. doi: 10.1016/j.jaci.2009.11.027.</citation>
    <PMID>20109729</PMID>
  </reference>
  <reference>
    <citation>Myles IA, Williams KW, Reckhow JD, Jammeh ML, Pincus NB, Sastalla I, Saleem D, Stone KD, Datta SK. Transplantation of human skin microbiota in models of atopic dermatitis. JCI Insight. 2016 Jul 7;1(10):e86955. doi: 10.1172/jci.insight.86955.</citation>
    <PMID>27478874</PMID>
  </reference>
  <reference>
    <citation>Bantz SK, Zhu Z, Zheng T. The Atopic March: Progression from Atopic Dermatitis to Allergic Rhinitis and Asthma. J Clin Cell Immunol. 2014 Apr;5(2):202. doi: 10.4172/2155-9899.1000202.</citation>
    <PMID>25419479</PMID>
  </reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>January 11, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <last_update_submitted>November 26, 2019</last_update_submitted>
  <last_update_submitted_qc>November 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 27, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lyophilized Biotherapeutic, Microbiome, Probiotic</keyword>
  <keyword>Commensal Gram-negative Bacteria</keyword>
  <keyword>Staphylococcus Aureus</keyword>
  <keyword>Transepidermal Water Loss</keyword>
  <keyword>Allergic Diseases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dermatitis, Atopic</mesh_term>
    <mesh_term>Dermatitis</mesh_term>
    <mesh_term>Eczema</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>June 9, 2020</submitted>
    <returned>June 24, 2020</returned>
    <submitted>August 10, 2020</submitted>
    <returned>August 26, 2020</returned>
    <submitted>February 25, 2021</submitted>
    <returned>March 16, 2021</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03018275
org study id: 170033
secondary id: 17-I-0033
nct id: NCT03018275
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Background:

      Atopic dermatitis (AD) is a skin disease also called eczema. It is common in children and
      sometimes gets better on its own. However, chronic AD may cause asthma, food allergies, eye
      infections, and sleep problems. The cause of AD might be related to bacteria that live on the
      skin. Researchers want to see if introducing bacteria, R mucosa, from healthy skin onto the
      skin of someone with AD helps treat the disease.

      Objective:

      To test the safety and activity of R mucosa for treating AD.

      Eligibility:

      Part 1: People ages 18 and older with AD

      Part 2: Children ages 3-17 with AD

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Examination of their AD

      Blood and urine tests

      At the baseline visit, participants will have blood tests and photos taken of their skin.
      They will get a supply of R mucosa and a memory aid to track their doses and record how they
      are feeling. Part 2 participants guardians will complete questionnaires about their child s
      AD.

      Part 1 participants will spray R mucosa on their arm twice per week for 6 weeks.

      Part 2 guardians will spray it on their child s arm twice per week for 16 weeks.

      Participants will have follow-up visits to repeat some baseline tests and review their memory
      aid:

      Part 1: Six weeks after the baseline visit

      Part 2: Four times over 16 weeks; then 2 or 3 times for 1 year

      Participants will be called or emailed to discuss how they are feeling:

      Part 1: About 30 days after their last visit

      Part 2: About every 10 days between visits
The underlying pathology of atopic dermatitis (AD) consists of defective skin barrier
      function, susceptibility to Staphylococcus aureus skin infection, and immune imbalance. There
      is currently no cure for AD. Preclinical data in a mouse model of AD suggest that commensal
      Gram-negative bacteria (CGN), such as Roseomonas mucosa, from a healthy source can relieve
      symptoms of AD and have antimicrobial effects. In this study, we will first evaluate the
      safety of R mucosa-based biotherapy in adults with AD (age 18+ years; part 1), and then
      evaluate the safety and activity of R mucosa-based biotherapy in children (ages 3-17 years)
      with AD (parts 2A and 2B). In part 1, participants will receive twice-weekly doses of CGN
      biotherapy for 6 weeks, with dose escalations at 2 and 4 weeks. In part 2, participants will
      receive twice-weekly doses of CGN biotherapy for 4 months, with possible dose escalations at
      4 and 8 weeks (part 2A only). Starting at 12 weeks for both parts 2A and 2B, dosing frequency
      may be increased to every other day. Participants in part 1 will be contacted 30 10 days
      after end of treatment for assessment of safety. Participants in parts 2A and 2B will also be
      followed for up to 1 year after the end of treatment for evaluation of long-term activity and
      safety. This will be the first study to test cutaneous live biotherapeutic products for AD.
      We hypothesize that altering the strains of CGN on the skin of people with AD will improve
      the patient s clinical outcome. We do not expect serious toxicities because R mucosa is
      rarely pathogenic; reported cases of bacteremia have typically been associated with
      percutaneous catheters in immunocompromised patients, who are excluded from this study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: A 50% reduction in antecubital-specific SCORing Atopic Dermatitis (SCORAD) with no adverse events related to product use. Frequency of solicited adverse events, unsolicited adverse events, serious adverse events, and death.
time frame: 4 weeks, 8 weeks, 12 weeks, 16 weeks, 8 months, 12 months, and 16 months
measure: A 30% improvement in the quality of life as measured by the validated Children's Dermatology Life Quality Index (CDLQI)
time frame: 4 weeks, 8 weeks, 12 weeks, 16 weeks, 8 months, 12 months, and 16 months
measure: A 30% improvement in the quality of life as measured by the validated Family Dermatology Life Quality Index (FDLQI)
time frame: 4 weeks, 8 weeks, 12 weeks, 16 weeks, 8 months, 12 months, and 16 months
arm group label: 1
arm group type: Experimental
description: Vials of lyophilized R mucosa (10"3, 10"4, or 10"5 CFU)
intervention type: Biological
intervention name: Roseomonas mucosa
description: R mucosa grown in Hank's balanced salt solution. Bacteria is washed, quantitated spectrophotometrically, suspended in 10%-15% sucrose, and lyophilized.
arm group label: 1
criteria: 
gender: All
minimum age: 3 Years
maximum age: 99 Years
healthy volunteers: No
last name: Ian A Myles, M.D.
role: Principal Investigator
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
facility: 
country: United States
citation: Boguniewicz M, Leung DY. Recent insights into atopic dermatitis and implications for management of infectious complications. J Allergy Clin Immunol. 2010 Jan;125(1):4-13; quiz 14-5. doi: 10.1016/j.jaci.2009.11.027.
PMID: 20109729
citation: Myles IA, Williams KW, Reckhow JD, Jammeh ML, Pincus NB, Sastalla I, Saleem D, Stone KD, Datta SK. Transplantation of human skin microbiota in models of atopic dermatitis. JCI Insight. 2016 Jul 7;1(10):e86955. doi: 10.1172/jci.insight.86955.
PMID: 27478874
citation: Bantz SK, Zhu Z, Zheng T. The Atopic March: Progression from Atopic Dermatitis to Allergic Rhinitis and Asthma. J Clin Cell Immunol. 2014 Apr;5(2):202. doi: 10.4172/2155-9899.1000202.
PMID: 25419479
responsible party type: Sponsor
mesh term: Dermatitis, Atopic
mesh term: Dermatitis
mesh term: Eczema
submitted: June 9, 2020
returned: June 24, 2020
submitted: August 10, 2020
returned: August 26, 2020
submitted: February 25, 2021
returned: March 16, 2021