THREAT: Testing Harms Related to Exposure to Allergenic and Epithelial Toxins

NCT07271381 | Recruiting

• 2 other identifiers: 10002257002257-I
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Allergic and inflammatory conditions have been increasing over the years. Many factors may play a role in this. Every day, people are exposed to pollution and chemicals in our foods, clothing, and all of the cleaning, hygiene, and other products we use. Studies have suggested there may be links between these environmental exposures and allergic and inflammatory illnesses. Researchers want to know more about how these exposures affect our health. Objective: To learn how everyday exposure to common substances affects people s health. Eligibility: Healthy people aged 18 to 80 years. Design: Participants will have 2 stays in the hospital. Each stay will last 7 days, and the stays will be spaced 4 to 6 weeks apart. During both stays, participants will remain confined to their room. They will eat only food from the menu, and they will use only provided products for personal care. (They may bring their own electronic devices, such as their phone and computer.) One stay will be in a pure room. Participants will breathe filtered air, eat unprocessed foods, and use personal care products with fewer chemicals. One stay will be in a room that allows exposure to common environmental chemicals. Some participants will be limited to only 1 type of exposure: chemicals thought to affect only skin, gut, or respiratory health. Some participants will be exposed to all 3 types. Participants will undergo testing. Blood, skin cell, urine, mouth swabs, and stool samples will be taken. They will have lung tests, smell tests, and tests that measure the health of their skin. These tests will be repeated in outpatient visits 2 weeks after each hospital stay....

Conditions

Allergic; Inflammatory

Keywords

Environmental Exposures; Skin barrier dysfunction; Skin impedance

Outcome Measures

Primary Outcomes (4)

• Cohort 1 (skin): The primary endpoint for the skin substudy is the skin impedance change response from the common environment.

  Cohort 1: Determine the effects of common vs. pure exposures on the skin in healthy volunteers.

  Baseline and completion of inpatient stay

• Cohort 2 (GI): The primary endpoint for the GI substudy is analogous to that of the skin substudy, except replacing skin impedance with the Shannon-Weaver diversity index measured on the gut microbiome that measures metabolic diversity.

  Cohort 2: Determine the effects of common vs. pure exposures on GI tract in healthy volunteers.

  Baseline and completion of inpatient stay

• Cohort 2 (Airway): The primary endpoint for the airway substudy is the airway maximum change response from the common environment minus the airway maximum change response from the pure environment.

  Cohort 3: Determine the effects of common vs. pure exposures on airway in healthy volunteers

  Baseline and completion of inpatient stay

• Based on combined exposures from all 3 organ systems and randomization design, repeat primary and secondary endpoint responses of Stage 1.

  Stage 2 Primary Objective: Determine the combined effects of skin, GI, and airway exposures of the respective organ systems in healthy volunteers.

  Baseline and completion of inpatient stay

Secondary Outcomes (9)

• Change metabolic functional analysis, and/or specific taxa of skin microbiome.

  Baseline and completion of inpatient stay.

• Change in skin metabolomics by tape strip analysis during study exposure.

  Baseline and completion of inpatient stay.

• Change in metabolic functional analysis, and/or specific taxa of gut microbiome.

  Baseline and completion of inpatient stay.

• Change in diversity index, metabolic functional analysis, and/or specific taxa of oral microbiome. Perform pair-wise and p-crest analysis.

  Baseline and completion of inpatient stay.

• Increase in airway resistance (using R5 or R5-R20) from admission to last day (or the maximum of the daily measurements) of inpatient stay by impulse oscillometry (IOS).

  Baseline and completion of inpatient stay.

Study Arms (6)

Common Airway

EXPERIMENTAL

Exposure to a sham air purifier, and wall art with foam and polyurethane.

Other: Environmental Exposures

Common Gastrointestinal

EXPERIMENTAL

Exposure to an ultra processed diet.

Other: Environmental Exposures

Common Skin

EXPERIMENTAL

Exposure to toothpaste, body wash, shampoo, and detergents containing sodium lauryl sulfate and other hazardous agents (commonly used likely toxic ingredients).

Other: Environmental Exposures

Pure Airway

OTHER

Exposure to wall art without foam and polyurethane.

Other: Control Exposures

Pure Gastrointestinal

OTHER

Exposure to a a minimally processed diet.

Other: Control Exposures

Pure Skin

OTHER

Exposure to SLS-free and toxin free toothpaste, body wash, shampoo, detergents, non-synthetic clothing, and sheets.

Other: Control Exposures

Interventions

Environmental Exposures OTHER

Toothpaste, skin lotion, hand soap, body wash, laundry detergent, shampoo containing sodium lauryl sulfate (SLS), wall art with foam and polyurethane, and processed food.

Common Airway; Common Gastrointestinal; Common Skin

Control Exposures OTHER

SLS-free, toxin free toothpaste, body wash, shampoo, detergents, non-synthetic clothing, and sheets, a minimally processed diet, and wall art without foam and polyurethane.

Pure Airway; Pure Gastrointestinal; Pure Skin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To participate in this study, an individual must meet all of the following criteria:
• Ability to provide informed consent.
• Age 18-80 years.
• Agreement to adhere to lifestyle considerations.
• Ability to exclusively adhere to UPD and MPD during inpatient stay.
• Ability to speak English.
• Willing to allow storage of samples and data for future research.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Diagnosis of atopic (physician-diagnosed asthma, AD, food allergy, chronic hives), autoimmune, metabolic, or chronic infectious or inflammatory diseases.
• Positive Phadiatop test.
• Current or history of neoplastic disease within 5 years.
• Current receipt of chemotherapy.
• HIV, hepatitis B, or hepatitis C infection.
• Receipt of any vaccine within 1 month prior to enrollment.
• Receipt of oral antibiotics within 3-6 months prior to enrollment.
• Use of topical, oral, or parental corticosteroids within 1 month prior to enrollment.
• Participation in another treatment or intervention study within 3 months prior to enrollment.
• Currently pregnant or lactating.
• Currently smoking or vaping.
• Any other condition or intercurrent illness deemed by the investigators to be of potential risk to the participant or validity of study results.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (12)

• Rinaldi AO, Korsfeldt A, Ward S, Burla D, Dreher A, Gautschi M, Stolpe B, Tan G, Bersuch E, Melin D, Askary Lord N, Grant S, Svedenhag P, Tsekova K, Schmid-Grendelmeier P, Mohrenschlager M, Renner ED, Akdis CA. Electrical impedance spectroscopy for the characterization of skin barrier in atopic dermatitis. Allergy. 2021 Oct;76(10):3066-3079. doi: 10.1111/all.14842. Epub 2021 May 15.

  PMID: 33830511 BACKGROUND

• Zeldin J, Chaudhary PP, Spathies J, Yadav M, D'Souza BN, Alishahedani ME, Gough P, Matriz J, Ghio AJ, Li Y, Sun AA, Eichenfield LF, Simpson EL, Myles IA. Exposure to isocyanates predicts atopic dermatitis prevalence and disrupts therapeutic pathways in commensal bacteria. Sci Adv. 2023 Jan 6;9(1):eade8898. doi: 10.1126/sciadv.ade8898. Epub 2023 Jan 6.

  PMID: 36608129 BACKGROUND

• Pat Y, Yazici D, D'Avino P, Li M, Ardicli S, Ardicli O, Mitamura Y, Akdis M, Dhir R, Nadeau K, Agache I, Ogulur I, Akdis CA. Recent advances in the epithelial barrier theory. Int Immunol. 2024 Apr 3;36(5):211-222. doi: 10.1093/intimm/dxae002.

  PMID: 38227765 BACKGROUND

• Yazici D, Ogulur I, Pat Y, Babayev H, Barletta E, Ardicli S, Bel Imam M, Huang M, Koch J, Li M, Maurer D, Radzikowska U, Satitsuksanoa P, Schneider SR, Sun N, Traidl S, Wallimann A, Wawrocki S, Zhakparov D, Fehr D, Ziadlou R, Mitamura Y, Bruggen MC, van de Veen W, Sokolowska M, Baerenfaller K, Nadeau K, Akdis M, Akdis CA. The epithelial barrier: The gateway to allergic, autoimmune, and metabolic diseases and chronic neuropsychiatric conditions. Semin Immunol. 2023 Nov;70:101846. doi: 10.1016/j.smim.2023.101846. Epub 2023 Oct 4.

  PMID: 37801907 BACKGROUND

• Akdis CA. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol. 2021 Nov;21(11):739-751. doi: 10.1038/s41577-021-00538-7. Epub 2021 Apr 12.

  PMID: 33846604 BACKGROUND

• Ogulur I, Pat Y, Aydin T, Yazici D, Ruckert B, Peng Y, Kim J, Radzikowska U, Westermann P, Sokolowska M, Dhir R, Akdis M, Nadeau K, Akdis CA. Gut epithelial barrier damage caused by dishwasher detergents and rinse aids. J Allergy Clin Immunol. 2023 Feb;151(2):469-484. doi: 10.1016/j.jaci.2022.10.020. Epub 2022 Dec 1.

  PMID: 36464527 BACKGROUND

• Sasaki M, Sundberg M, Frei R, Ferstl R, Heye KN, Willems EP, Akdis CA, Lauener R; CK-CARE Study Group; Roduit C. Electrical impedance spectroscopy detects skin barrier dysfunction in childhood atopic dermatitis. Allergy. 2024 Jan;79(1):142-152. doi: 10.1111/all.15895. Epub 2023 Sep 27.

  PMID: 37753955 BACKGROUND

• Yadav M, Chaudhary PP, D'Souza BN, Ratley G, Spathies J, Ganesan S, Zeldin J, Myles IA. Diisocyanates influence models of atopic dermatitis through direct activation of TRPA1. PLoS One. 2023 Mar 6;18(3):e0282569. doi: 10.1371/journal.pone.0282569. eCollection 2023.

  PMID: 36877675 BACKGROUND

• Whelan K, Bancil AS, Lindsay JO, Chassaing B. Ultra-processed foods and food additives in gut health and disease. Nat Rev Gastroenterol Hepatol. 2024 Jun;21(6):406-427. doi: 10.1038/s41575-024-00893-5. Epub 2024 Feb 22.

  PMID: 38388570 BACKGROUND

• Galant SP, Komarow HD, Shin HW, Siddiqui S, Lipworth BJ. The case for impulse oscillometry in the management of asthma in children and adults. Ann Allergy Asthma Immunol. 2017 Jun;118(6):664-671. doi: 10.1016/j.anai.2017.04.009.

  PMID: 28583260 BACKGROUND

• Malvehy J, Hauschild A, Curiel-Lewandrowski C, Mohr P, Hofmann-Wellenhof R, Motley R, Berking C, Grossman D, Paoli J, Loquai C, Olah J, Reinhold U, Wenger H, Dirschka T, Davis S, Henderson C, Rabinovitz H, Welzel J, Schadendorf D, Birgersson U. Clinical performance of the Nevisense system in cutaneous melanoma detection: an international, multicentre, prospective and blinded clinical trial on efficacy and safety. Br J Dermatol. 2014 Nov;171(5):1099-107. doi: 10.1111/bjd.13121. Epub 2014 Oct 19.

  PMID: 24841846 BACKGROUND

• Redruello-Requejo M, Del Mar Blaya M, Gonzalez-Reguero D, Robas-Mora M, Arranz-Herrero J, Partearroyo T, Varela-Moreiras G, Penalba-Iglesias D, Jimenez-Gomez P, Reche-Sainz P. Cross-Sectional Comparative Analysis of Gut Microbiota in Spanish Adolescents with Mediterranean and Western Diets. Nutrients. 2025 Jan 22;17(3):388. doi: 10.3390/nu17030388.

  PMID: 39940246 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

Environmental Exposure

Intervention Hierarchy (Ancestors)

Environmental Pollution; Public Health; Environment and Public Health

Study Officials

• Hirsh D Komarow, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jodi L Blake, R.N.

CONTACT

(301) 605-2896; jodi.blake@nih.gov

Hirsh D Komarow, M.D.

CONTACT

(301) 594-2197; komarowh@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2025
• First Posted: December 9, 2025
• Study Start: April 15, 2026
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): January 30, 2031
• Last Updated: April 28, 2026

Record last verified: 2026-04-23

Locations

US (1)