Clinical trial NCT03450031: Evaluation of Nasal Inflammatory Biomarkers
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Seasonal Allergic Rhinitis
Lead sponsor: Fraunhofer-Institute of Toxicology and Experimental Medicine
Sponsor class: OTHER
Collaborators: name: UCB Pharma
First posted: 2018-03-01
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Interleukin-4
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Fraunhofer ITEM im CRC
state: Niedersachsen
Study officials:
affiliation: Fraunhofer-Institute of Toxicology and Experimental Medicine
name: Jens Hohlfeld
role: PRINCIPAL_INVESTIGATOR
References: