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Longitudinal Endotyping Of Atopic Dermatitis Through Transcriptomic Skin Analysis (LEADS)

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ClinicalTrials.gov Identifier: NCT05436535
Recruitment Status : Not yet recruiting
First Posted : June 29, 2022
Last Update Posted : August 26, 2022
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:

This is a multi-center, longitudinal study which will characterize the gene expression profiles and transcriptomic endotypes that underlie mild and moderate-severe Atopic dermatitis (AD) and will determine changes in these expression patterns and endotypes in response to standard-of-care treatment. Participants will complete up to nine study visits with assessment of topical steroid response and dupilumab response (if uncontrolled with topical steroids). Skin samples will be collected at all study visits to determine the gene expression profiles and transcriptomic endotypes that underlie mild vs. moderate-severe AD disease. The investigators will also evaluate the lipidomic, metabolomic, proteomic, and microbiome profiles of AD skin endotypes associated with mild and moderate-severe AD disease. Non-AD participants will serve as a control population.

The primary objective of this study is to determine if the type 2-high non-lesional skin (skin tape) endotype is associated with current mild versus moderate-severe AD disease.


Condition or disease Intervention/treatment Phase
Atopic Dermatitis Biological: Dupilumab Drug: Vanicream Drug: Triamcinolone Acetonide Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Longitudinal Endotyping Of Atopic Dermatitis Through Transcriptomic Skin Analysis (ADRN-12)
Estimated Study Start Date : September 30, 2022
Estimated Primary Completion Date : September 15, 2024
Estimated Study Completion Date : May 15, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eczema
Drug Information available for: Dupilumab

Arm Intervention/treatment
Experimental: Dupilumab-naïve atopic dermatitis participants

On Day 7, dupilumab-naïve AD participants will begin applying triamcinolone 0.1% ointment (provided by the study) twice daily to the specified target area. Additionally, dupilumab-naïve AD participants will apply triamcinolone 0.1% ointment (non-sensitive regions)/ hydrocortisone 2.5% ointment (sensitive regions) twice daily to active lesions on non-target skin.

Dupilumab-naïve AD participants will return for a Steroid Assessment Visit at Day 35, when response to triamcinolone will be evaluated at the target site by TAA and targeted EASI scoring, and overall management of AD body-wide by topical steroid/moisturizer treatment will be evaluated by EASI score.

Biological: Dupilumab
Adult dupilumab-naïve topical steroid non-responder (EASI >7) participants beginning treatment with dupilumab will initially receive a loading dose of two 300 mg subcutaneous injections. The two injections will be administered at different sites in the abdomen, thighs, or upper arms. Pediatric dupilumab-naïve topical steroid non-responder participants beginning treatment with dupilumab will receive a loading dose, according to their weight
Other Name: Dupixent

Drug: Triamcinolone Acetonide
On Day 7, dupilumab-naïve AD participants will begin applying triamcinolone 0.1% ointment (provided by the study) twice daily to the specified target area. Additionally, dupilumab-naïve AD participants will apply triamcinolone 0.1% ointment (non-sensitive regions)/ hydrocortisone 2.5% ointment (sensitive regions) twice daily to active lesions on non-target skin

Experimental: Experienced Dupilumab atopic dermatitis participants

AD participants already on dupilumab (for >= 4 months prior to study entry (20 children, 40 adults)) at the start of the study will continue dupilumab treatment as prescribed by their physician outside of the study.

After Day 7, long-term dupilumab participants may continue to apply topical steroids/moisturizer body-wide as needed per their physician's orders and will return for assessments and sampling at Days 63 and 140. At Day 140, participants will discontinue applying topical steroids to the specified target area and begin to apply Vanicream™ at least twice daily on the target skin area until their End of Study Assessment visit (Day 168)

Drug: Vanicream
Participants will apply Vanicream at least twice daily to the specified target skin area starting at Day 140 through the End of Study Assessment Visit

Active Comparator: Non-atopic dermatitis participants

Approximately 150 will be non-AD controls (including approximately 50 children, 6-17 years of age, and 100 adults, = 18 years of age)

Non-AD control participants will return for assessment visits at Days 0, 7, 35, 91, 140, and 168. Non-AD participants will apply Vanicream (TM) at least twice daily to the specified target skin area starting at Day 140 through the End of Study Assessment Visit (Day 168)

Drug: Vanicream
Participants will apply Vanicream at least twice daily to the specified target skin area starting at Day 140 through the End of Study Assessment Visit




Primary Outcome Measures :
  1. Non-lesional skin tape transcriptome at Day 7 [ Time Frame: At Day 7 ]
    Skin biopsies from non-lesional sites will be enzymatically digested using an adaptation of a recently developed cold active protease treatment method. A fraction of cells will be cryopreserved and will be later used for the single cell transcriptome RNAseq


Secondary Outcome Measures :
  1. Non-lesional and lesional skin tape transcriptome at Day 7 and Days 168-224 [ Time Frame: At Day 7 and Days 168-224 ]
    Skin biopsies from lesional and non-lesional sites will be enzymatically digested using an adaptation of a recently developed cold active protease treatment method. A fraction of cells will be cryopreserved and will be later used for the single cell transcriptome RNAseq



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

All Participants:

  1. Participant and/or parent guardian must be able to understand and provide informed consent and assent (if applicable)
  2. Participants must agree to apply a stable dose of a study provided topical moisturizer (Vanicream (TM)) at least twice daily between the Baseline Assessment and Day 7 Visits to a specified skin target area
  3. Individuals with asthma must adhere to asthma controller medication(s) for the duration of the study
  4. Females of child-bearing potential who do not self-report as pregnant must have a negative pregnancy test at the Baseline Assessment and Day 7 Visits.
  5. Females of child-bearing and sexually active must agree to use Food and Drug Administration (FDA) approved methods of birth control for the duration of the study. These include hormonal contraceptives, intrauterine device, double barrier contraception (i.e., condom plus diaphragm), or male partner with documented vasectomy
  6. Participant and/or parent guardian must be able to understand and complete study-related questionnaires

Non-Atopic dermatitis (AD) Participants:

1. No history of AD or food allergy as diagnosed by a physician

AD Participants:

  1. A history of Chronic AD, (according to the Atopic Dermatitis Research Network [ADRN] Standard Diagnostic Criteria), that has been present for at least 1 year before the Screening Visit
  2. Must agree to refrain from applying topical steroid to a specified target area between the Baseline Assessment and Day 7 Visit
  3. Dupilumab-naïve AD participants must have active lesions on the upper or lower extremities or trunk of sufficient size (36 cm^2 area for participants >= 18 years of age, and 32 cm^ 2 for participants < 18 years of age) for specimen collection at the Baseline Assessment and at the Steroid Initiation (Day 7) Visits. The required area may be one contiguous area or may encompass multiple areas
  4. Long-term dupilumab participants must be currently receiving dupilumab and must have started dupilumab treatment >= 4 months prior to the Screening Visit

Exclusion Criteria:

  1. Inability or unwillingness of a participant or parent guardian to comply with study protocol
  2. Weight less than 15 kg
  3. Known systemic hypersensitivity to any of the excipients of the study treatments (Vanicream (TM), hydrocortisone, triamcinolone, or dupilumab)
  4. Have any skin disease other than Atopic dermatitis (AD) that might compromise the stratum corneum barrier (e.g., bullous diseases, psoriasis, cutaneous T cell lymphoma [also called Mycosis Fungoides or Sezary syndrome], dermatitis herpetiformis, Hailey-Hailey, or Darier's disease)
  5. Known or suspected immunosuppression, including history of invasive opportunistic infections (e.g.

    tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution, or otherwise recurrent immune-compromised status, as judged by investigator

  6. Known history of human immunodeficiency virus (HIV) infection
  7. Ocular disorder that in the opinion of the investigator could adversely affect the individual's risk for study participation. Examples include, but are not limited to, individuals with a history of or active case of herpes keratitis; Sjogren's Syndrome, Keratoconjunctivitis Sicca, or Dry Eye Syndrome that require daily use of supplemental lubrication; or individuals with ocular conditions that require the regular use of ocular corticosteroids or cyclosporine
  8. Parasitic infection, except for vaginal trichomoniasis, within 12 months of the Screening Visit, or high risk for contracting parasitic infections (e.g. living in or traveling to endemic areas)
  9. History of malignancy within 5 years before the Screening Visit (completely treated in situ carcinoma of the cervix, and completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin or melanoma in situ are not exclusionary)
  10. History of non-malignant lymphoproliferative disorders
  11. History of alcohol or drug abuse within 2 years before the Screening Visit
  12. History of keloid formation (exclusionary for adult participants only)
  13. History of serious life-threatening reaction to tape or adhesives
  14. Individuals with asthma who have required use of a systemic corticosteroid within 3 months prior to the Baseline Assessment Visit or who require a dose greater than 880 mcg/day of fluticasone propionate or equivalent inhaled corticosteroid to maintain asthma control
  15. Past or current medical problems or findings from physical examination 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. This includes hypersensitivity to local anesthetics (e.g., lidocaine or Novocain), bleeding disorders, treatment with anticoagulants or other conditions in adult participants that would make the biopsy procedure inadvisable
  16. Planned major surgical procedure during study participation that could affect study participation or outcome assessment, per PI discretion
  17. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks before the Baseline Assessment Visit, or superficial skin infection within 1 week before the Baseline Assessment Visit
  18. Pregnant or breast-feeding women, or women planning to become pregnant or breastfeed during the study
  19. Use of any systemic (oral, intravenous (IV), intramuscular (IM)) immunosuppressive/immunomodulating therapies (e.g. steroids, cyclosporine, Janus kinase inhibitors, mycophenolate, azathioprine, or methotrexate) within 4 Weeks of the Baseline Assessment Visit, or any condition that, in the opinion of the investigator, will likely require such treatment(s) during study participation
  20. Treatment with biologics (other than dupilumab) as follows:

    1. Any cell-depleting agents, including but not limited to rituximab, within 6 months before the Baseline Assessment Visit, or until lymphocyte and CD 19+ lymphocyte count returns to normal, whichever is longer
    2. Omalizumab, Infliximab, adalimumab, golimumab, certolizumab pegol, abatacept, etanercept, anakinra within 16 weeks before the Baseline Assessment Visit for any indication
    3. Other biologics within 5 half-lives (if known) or 16 weeks before the Baseline Assessment Visit, whichever is longer
  21. Treatment with a live (attenuated) vaccine within 6 weeks before the Baseline Assessment Visit or planning to receive a live vaccine during the study
  22. Ongoing participation in an investigational trial or use of an investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, before the Baseline Assessment Visit
  23. Use of phototherapy (such as narrowband ultraviolet B [NBUVB], ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + UVA [PUVA]) or a tanning booth/parlor within 4 weeks of the Baseline Assessment Visit.
  24. Treatment with bleach bath within 1 week before the Baseline Assessment Visit
  25. Use of a chlorinated hot tub within 1 week before the Baseline Assessment Visit
  26. Initiation of treatment with prescription moisturizers or moisturizers containing ceramide, hyaluronic acid, urea, or filaggrin (FLG) during the study period (participants may continue using stable doses of such moisturizers on body areas other than the target area if initiated before the Baseline Assessment Visit)
  27. Planned or anticipated use of any prohibited medications or procedures during study participation.

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): NCT05436535


Locations
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United States, California
University of California, San Diego: Dermatology Clinical Trials Unit
La Jolla, California, United States, 92093
Children's Hospital Los Angeles: Division of Clinical Immunology & Allergy
Los Angeles, California, United States, 90027
United States, Colorado
National Jewish Health: Division of Pediatric Allergy and Clinical Immunology
Denver, Colorado, United States, 80206
United States, Massachusetts
Boston Children's Hospital: Department of Immunology
Boston, Massachusetts, United States, 02215
United States, New York
Icahn School of Medicine at Mount Sinai: Department of Pediatrics Allergy & Immunology
New York, New York, United States, 10029
University of Rochester Medical Center: Department of Dermatology
Rochester, New York, United States, 14642
United States, North Carolina
North Carolina Children's Hospital: Department of Pediatrics, Division of Allergy, Immunology and Rheumatology
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cincinnati Children's Hospital Medical Center: Asthma Center
Cincinnati, Ohio, United States, 45229
United States, Oregon
Oregon Health & Science University: Department of Dermatology
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania, Perelman Center for Advanced Medicine: Department of Dermatology
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Study Chair: Donald Leung, M.D., Ph.D. National Jewish Health: Division of Pediatric Allergy and Clinical Immunology
Study Chair: Max A. Seibold, Ph.D. National Jewish Health: Division of Pediatric Allergy and Clinical Immunology
Additional Information:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT05436535    
Other Study ID Numbers: DAIT ADRN-12
First Posted: June 29, 2022    Key Record Dates
Last Update Posted: August 26, 2022
Last Verified: August 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Dermatitis, Atopic
Dermatitis
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Triamcinolone
Triamcinolone Acetonide
Triamcinolone hexacetonide
Triamcinolone diacetate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action