Evaluation of Nasal Inflammatory Biomarkers

Evaluation of Nasal Inflammatory Biomarkers During the Early and Late Phase Response to Nasal Volus Allergen Challenge in in Subjects With Seasonal Allergic Rhinitis (Out-of-season)

This research aims to establish a panel of inflammatory biomarkers of the early (Histamine, Tryptase, ProstaglandineD2) and late (Interleukin-4, Interleukin-5, Interleukin-6, Interleukin-13, Eotaxin, Tumor necrosis factor-a (TNF), (Macrophage Inflammatory Protein-1beta (MIP1ß)) phase response to nasal bolus allergen challenge (NAC) in subjects with out-of-season seasonal allergic rhinitis, suitable for future application in drug intervention studies of novel anti-allergy therapeutics.

Study Overview

• Status: Completed
• Conditions: Seasonal Allergic Rhinitis
• Intervention / Treatment: Other: NAC (no drug/no device)

Detailed Description

Biomarkers will be sampled by nasal filter paper (NFP) adsorption and lavage (NLF) prior to and following NAC. Samples from initial subjects (Cohort A; n~6) will be used primarily for validation of biomarker assays in nasal filter paper eluates. Validated biomarker assays will be applied to analyze biomarker changes in a further cohort of subjects (Cohort B; n~12) with the aim of fully defining the optimum panel and sampling time points for future studies.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30165
      • Fraunhofer ITEM im CRC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able and willing to give written informed consent.

2. Male or female, age 18-65 years.

   Women will be considered for inclusion if they are:

   • Not pregnant, as confirmed by pregnancy test, and not nursing.
   • Of non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is pre-menarchal, or post-menopausal with documented proof of hysterectomy or tubal ligation, or meets clinical criteria for menopause and has been amenorrhoeic for more than 1 year prior to the screening visit).

   • Of childbearing potential and using a highly effective method of contraception during the entire study, as defined by at least one of the following

     • vasectomised partner
     • sexual abstinence (the lifestyle of the female should be such that there is complete abstinence from intercourse from two weeks prior to Visit 2 procedures until at least 72 hours after NAC)
     • implants, injectables, combined oral contraceptives, hormonal IUDs or double-barrier methods (i.e. any double combination of IUD, condom with spermicidal gel, diaphragm, sponge, and cervical cap)
3. History of seasonal allergic rhinitis to grass pollen with symptoms during the 2016 and 2017 allergen season requiring treatment with anti-histamines, nasal corticosteroids or leukotriene antagonists.
4. Absence of significant current symptoms of allergic rhinitis consistent with being out of season for their principal allergen (eg grass).
5. Skin prick test positive for mixed grass pollen allergen at Visit 1 or within one year prior to screening.

Exclusion criteria

1. Asthma requiring more than inhaled short-acting beta-2 agonists.
2. Spirometry showing FEV1 <80% predicted
3. Subjects who have smoked more than 5 cigarettes in the last 6 months or have a smoking history of ≥10 pack years.
4. Upper or lower respiratory tract infection in the prior 4 weeks.
5. Nasal or lung provocation procedure (eg, allergen challenge) conducted in the prior 4 weeks.
6. Significant nasal deformity, recent nasal surgery or obstructing nasal polyps.
7. History of anaphylaxis (any cause), or previous severe hypersensitivity reaction to any of the test agents for SPT or NAC.
8. Recent participation in a study of an investigational medicinal product (IMP) which could interfere with markers evaluated in this research
9. Use of any medications according to section 5.2 in the period indicated before Visit 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: NAC (no drug/no device) and NFP; NAC with mixed grass pollen will be conducted. Nasal mucosal inflammatory mediators will be collected via nasal filter paper (NFP)	Other: NAC (no drug/no device); Nasal allergen challenge (NAC) with mixed grass pollen: a bolus NAC with mixed grass pollen will be conducted
EXPERIMENTAL: NAC (no drug/no device) and NFP AND NLF; NAC with mixed grass pollen will be conducted. Nasal filter paper (NFP)sampling will be conducted from one nostril per time point. Subjects in Cohort B will also undergo nasal lavage (NLF) pre-NAC and at serial time points thereafter up to 8 hours	Other: NAC (no drug/no device); Nasal allergen challenge (NAC) with mixed grass pollen: a bolus NAC with mixed grass pollen will be conducted

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interleukin-4	Interlukin- 4 [pg/ml] using ELISA assays	Change from baseline at time points: 1 minutes (min), 4 min, 7 min, 10 min, 15 min, 30 min, 60 min, 120 min, 240 min, 360 min, 480 min

Collaborators and Investigators

• Sponsor: Fraunhofer-Institute of Toxicology and Experimental Medicine
• Collaborators: UCB Pharma
• Investigators: Principal Investigator: Jens Hohlfeld, Fraunhofer-Institute of Toxicology and Experimental Medicine

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 8, 2018
• Primary Completion (ACTUAL): April 26, 2018
• Study Completion (ACTUAL): October 30, 2018

Study Registration Dates

• First Submitted: January 30, 2018
• First Submitted That Met QC Criteria: February 22, 2018
• First Posted (ACTUAL): March 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 13, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal
• Other Study ID Numbers: 17-13 XOBIO Pilot

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No