Nasal Mucus Proteome and Immunotherapy

• ClinicalTrials.gov Identifier: NCT02159404
• Recruitment Status: Recruiting
• First Posted: June 9, 2014
• Last Update Posted: March 10, 2023
• Sponsor: Medical University of Graz
• Information provided by (Responsible Party): Tomazic Peter Valentin, MD, Medical University of Graz

Tracking Information

• First Submitted Date: June 5, 2014
• First Posted Date: June 9, 2014
• Last Update Posted Date: March 10, 2023
• Study Start Date: April 2015
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 20, 2018)

AUC of protein spectra obtained by mass spectrometry [ Time Frame: 3 years ]

Areas under the curve of protein spectra will be determined

• Original Primary Outcome Measures (submitted: June 5, 2014): identification of biomarkers [ Time Frame: 3 years ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Nasal Mucus Proteome and Immunotherapy
• Official Title: Seasonal Differences in Nasal Mucus Proteome and Impact of Immunotherapy

Brief Summary

Nasal mucus as first line defense barrier of the nasal mucosa contains a variety of proteins that act as functional units. We recently showed that the nasal mucus proteome between allergic rhinitis patients and healthy controls is significantly altered.

The aim of the present project is to show changes in nasal mucus proteome between allergic rhinitis patients and healthy controls over the pollen and non pollen season and to further determine whether and if so how the proteome changes under immunotherapy. Patients and healthy controls will be enrolled at two time points namely during the pollen season and out of the pollen season. Statistical differences will be determined within the groups and between the groups as well as impact of immunotherapy on patients undergoing therapy.

Mucus will be collected with a special suction device equipped with a mucus trap. Then, proteomic analysis will be performed by LC MS/MS mass spectrometry. Database search will identify distinct proteins and their function, origin etc. will be annotated. Protein groups will be analyzed through pathway enrichment and cluster analysis. Furthermore, mechanisms of immunotherapy in responders and success or failure of therapy could be determined. These could lead to the identification of potential biomarkers.

Detailed Description

Nasal mucus as first line defense barrier of the nasal mucosa contains a variety of proteins that act as functional units. We recently showed that the nasal mucus proteome between allergic rhinitis patients and healthy controls is significantly altered. On protein level, immune response in allergic rhinitis is enhanced and barrier function is reduced as reflected by increased epithelial permeability. Moreover, there is an unfavorable imbalance in innate anti-proteases. Proteases in pollen grain could therefore not be adequately deactivated in the mucus further damaging the epithelium which leads to submucosal penetration of allergens and facilitated presentation to antigen presenting cells.

The aim of the present project is to show changes in nasal mucus proteome between allergic rhinitis patients and healthy controls over the pollen and non pollen season and to further determine whether and if so how the proteome changes under immunotherapy. For the first aim patients and healthy controls will be enrolled at two time points namely during the pollen season and out of the pollen season. Statistical differences will be determined within the groups and between the groups. The protein changes over the time course reflect how allergics but also healthy controls react to allergen challenge. The results should give insight on possible biomarkers that could be used for diagnostics and therapy. Protein substitution or inhibition may be a future therapy to reinforce the barrier function of nasal mucus and treat allergic rhinitis symptoms. The effect of immunotherapy as sole causal therapy will be determined and therapy responders will be compared to non-responders. We hypothesize that responders will show proteome changes similar to healthy conditions. This further concretizes distinct proteins as biomarkers that could be used as therapeutic agents. Moreover proteome changes could be used to predict and monitor therapeutic success or failure and patients may be stratified to be subjected to other therapeutic strategies than immunotherapy saving time and money.

Mucus will be collected with a special suction device equipped with a mucus trap. Then, proteomic analysis will be performed by LC MS/MS mass spectrometry. Database search will identify distinct proteins and their function, origin etc. will be annotated. Protein groups will be analyzed through pathway enrichment and cluster analysis. By this means complex proteomic data can be visualized for a better understanding of global changes in protein networks and functions.

Investigating the nasal mucus proteome in diseased and healthy state leads to a better understanding of its barrier function and reaction to allergens. Distinct proteins and/or proteins groups could be used as biomarkers for novel diagnostic and therapeutic approaches. Furthermore, mechanisms of immunotherapy in responders and success or failure of therapy could be determined.

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Patients with Allergic Rhinoconjunctivitis Healthy controls
• Condition: Allergic Rhinoconjunctivitis
• Intervention: Biological: Immunotherapy

Study Groups/Cohorts

• Allergic Rhinoconjunctivitis
  Patients with diagnosed Allergic Rhinoconjunctivitis
  Intervention: Biological: Immunotherapy
• Healthy controls

• Publications *: Tomazic PV, Birner-Gruenberger R, Leitner A, Obrist B, Spoerk S, Lang-Loidolt D. Nasal mucus proteomic changes reflect altered immune responses and epithelial permeability in patients with allergic rhinitis. J Allergy Clin Immunol. 2014 Mar;133(3):741-50. doi: 10.1016/j.jaci.2013.09.040. Epub 2013 Nov 28.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 5, 2014): 88
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 1, 2024
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• pollen allergy verified by skin-prick test, blood tests for specific IgE (RAST) and allergic rhinitis symptoms, eligible for immunotherapy

Exclusion Criteria:

• chronic infectious diseases, bad overall health condition, pregnancy, long-term intake of nasal and/or systemic steroids or antihistamines, acute and/or chronic rhinosinusitis and parallel participation in other studies

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Peter V Tomazic, M.D.; +4331638581347 ext +4331638583448; peter.tomazic@medunigraz.at

• Listed Location Countries: Austria

Administrative Information

• NCT Number: NCT02159404
• Other Study ID Numbers: ProtOmicsSeasons01; KLI 425-B23 ( Other Grant/Funding Number: Austrian Science Fund (FWF) )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Tomazic Peter Valentin, MD, Medical University of Graz
• Original Responsible Party: Same as current
• Current Study Sponsor: Medical University of Graz
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Medical University of Graz
• Verification Date: March 2023