NCT02688478

Brief Summary

Phthalates are commonly used plasticizers that have been linked to asthma in epidemiological studies. The investigators are researching effects of phthalates on airway immunology and lung function, and on allergic responses by doing an inhaled allergen challenge. After exposing participants to either filtered air or carefully controlled levels of phthalate in our exposure chamber we will collect samples from the nose and the upper airways, by rinsing the nose with saltwater or performing small brushings. The investigators will also collect a bronchial samples by bronchoscopy after each exposure. After 2 weeks, the entire procedure will be repeated with the alternate exposure.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
20

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Feb 2017

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 6, 2016

Completed
2 months until next milestone

First Posted

Study publicly available on registry

February 23, 2016

Completed
12 months until next milestone

Study Start

First participant enrolled

February 2, 2017

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 7, 2020

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

May 7, 2021

Completed
Last Updated

August 2, 2019

Status Verified

July 1, 2019

Enrollment Period

3.3 years

First QC Date

January 6, 2016

Last Update Submit

July 31, 2019

Conditions

Allergies

Keywords

PhthalateDibutylphthalate (DBP)Airway responsivenessAllergies

Outcome Measures

Primary Outcomes (4)

  • Recruitment of immune cells in airways

    Recruitment will be identified by performing differential cell counts

    3-24 hours

  • Activation of immune cells in airways

    Cellular activation will be measured by cytokine expression in airway samples.

    3-24 hours

  • Airway responsiveness

    Airway responsiveness will be measured by spirometry.

    3-24 hours

  • Airway Inflammation

    Airway Inflammation will be measured by Fractional exhaled NO.

    3-24 hours

Secondary Outcomes (4)

  • Allergen specific IgE

    24 hours

  • Inflammatory markers in plasma and cell function after in vitro stimulation with inflammatory ligands (LPS & R848)

    3-24h

  • Response of immune cells in blood

    3-24 hours

  • Response of immune cells in airways

    3-24 hours

Study Arms (2)

Filtered air

ACTIVE COMPARATOR

Exposure for 3 hours to filtered air followed by subject specific inhaled allergen challenge

Other: Filtered AirOther: Allergen

Phthalate

EXPERIMENTAL

Exposure for 3 hours to dibutyl phthalate followed by subject specific inhaled allergen challenge

Other: PhthalateOther: Allergen

Interventions

PhthalateOTHER

Delivered by inhalation on day 1 of the triad

Also known as: DBP
Phthalate
Filtered AirOTHER

Delivered by inhalation on day 1 of the triad

Filtered air
AllergenOTHER

Subject specific allergen is delivered by inhalation on day 1 of the triad

Filtered airPhthalate

Eligibility Criteria

Age19 Years - 49 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Age between 19 and 49 years.
  • Non-smoking.
  • Proficient in English
  • Positive skin prick test for at least one of: birch, grass, or dust.
  • Healthy, or diagnosed with mild asthma

You may not qualify if:

  • pregnancy/breastfeeding
  • unstable asthma symptoms (eg: exacerbations in previous 2 weeks)
  • use of inhaled corticosteroids or bronchodilator medication more than 3 times a week
  • presence of co-existing medical conditions i.e. arrythmia (as assessed by the primary investigator)
  • participation in another study that involves taking medications
  • regular use of antihistamines, non-steroidal anti-inflammatories, anticoagulants, acetylsalicylic acid (ASA) or decongestants
  • allergy to salbutamol or lidocaine.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of British columbia

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Related Publications (11)

  • Wormuth M, Scheringer M, Vollenweider M, Hungerbuhler K. What are the sources of exposure to eight frequently used phthalic acid esters in Europeans? Risk Anal. 2006 Jun;26(3):803-24. doi: 10.1111/j.1539-6924.2006.00770.x.

    PMID: 16834635BACKGROUND

  • Wittassek M, Koch HM, Angerer J, Bruning T. Assessing exposure to phthalates - the human biomonitoring approach. Mol Nutr Food Res. 2011 Jan;55(1):7-31. doi: 10.1002/mnfr.201000121.

    PMID: 20564479BACKGROUND

  • Kocbach Bolling A, Holme JA, Bornehag CG, Nygaard UC, Bertelsen RJ, Nanberg E, Bodin J, Sakhi AK, Thomsen C, Becher R. Pulmonary phthalate exposure and asthma - is PPAR a plausible mechanistic link? EXCLI J. 2013 Aug 20;12:733-59. eCollection 2013.

    PMID: 26622216BACKGROUND

  • Jaakkola JJ, Knight TL. The role of exposure to phthalates from polyvinyl chloride products in the development of asthma and allergies: a systematic review and meta-analysis. Environ Health Perspect. 2008 Jul;116(7):845-53. doi: 10.1289/ehp.10846.

    PMID: 18629304BACKGROUND

  • Deutschle T, Reiter R, Butte W, Heinzow B, Keck T, Riechelmann H. A controlled challenge study on di(2-ethylhexyl) phthalate (DEHP) in house dust and the immune response in human nasal mucosa of allergic subjects. Environ Health Perspect. 2008 Nov;116(11):1487-93. doi: 10.1289/ehp.11474. Epub 2008 Jul 7.

    PMID: 19057701BACKGROUND

  • Kolarik B, Lagercrantz L, Sundell J. Nitric oxide in exhaled and aspirated nasal air as an objective measure of human response to indoor air pollution. Indoor Air. 2009 Apr;19(2):145-52. doi: 10.1111/j.1600-0668.2008.00572.x. Epub 2008 Dec 11.

    PMID: 19077172BACKGROUND

  • Peters,S., Shaver,J., & Zangrilli,J.G. Airway responses to antigen in asthmatic and nonasthmatic subjects in Inflammatory mechanisms in asthma (eds. Holgate,S.T. & Busse,W.W.) (Marcel Dekker, New York, 2014).

    BACKGROUND

  • Hoppin JA, Ulmer R, London SJ. Phthalate exposure and pulmonary function. Environ Health Perspect. 2004 Apr;112(5):571-4. doi: 10.1289/ehp.6564.

    PMID: 15064163BACKGROUND

  • Just AC, Whyatt RM, Miller RL, Rundle AG, Chen Q, Calafat AM, Divjan A, Rosa MJ, Zhang H, Perera FP, Goldstein IF, Perzanowski MS. Children's urinary phthalate metabolites and fractional exhaled nitric oxide in an urban cohort. Am J Respir Crit Care Med. 2012 Nov 1;186(9):830-7. doi: 10.1164/rccm.201203-0398OC. Epub 2012 Aug 23.

    PMID: 22923660BACKGROUND

  • Leung C, Ryu MH, Bolling AK, Maestre-Batlle D, Rider CF, Huls A, Urtatiz O, MacIsaac JL, Lau KS, Lin DTS, Kobor MS, Carlsten C. Peroxisome proliferator-activated receptor gamma gene variants modify human airway and systemic responses to indoor dibutyl phthalate exposure. Respir Res. 2022 Sep 16;23(1):248. doi: 10.1186/s12931-022-02174-8.

    PMID: 36114491DERIVED

  • Maestre-Batlle D, Huff RD, Schwartz C, Alexis NE, Tebbutt SJ, Turvey S, Bolling AK, Carlsten C. Dibutyl Phthalate Augments Allergen-induced Lung Function Decline and Alters Human Airway Immunology. A Randomized Crossover Study. Am J Respir Crit Care Med. 2020 Sep 1;202(5):672-680. doi: 10.1164/rccm.201911-2153OC.

    PMID: 32320637DERIVED

MeSH Terms

Conditions

Hypersensitivity

Interventions

phthalic acidAllergens

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

AntigensBiological Factors

Study Officials

  • Christopher Carlsten, MD, MPH

    University of British Columbia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

January 6, 2016

First Posted

February 23, 2016

Study Start

February 2, 2017

Primary Completion

May 7, 2020

Study Completion

May 7, 2021

Last Updated

August 2, 2019

Record last verified: 2019-07

Locations

CA(1)