Development of a Novel Non-invasive Inflammometry Following Allergen Challenge in Patients With Mild Allergic Asthma

NCT06317909 | Recruiting

• 1 other identifier: 23-03 DONNER-2
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this exploratory method-development study is to to establish and evaluate novel non-invasive methods to monitor airway inflammation induced by allergen challenge (both by instillation during bronchoscopy and by inhalation) in patients with mild allergic asthma. The investigator wants to further profile and develop the allergen challenge model by investigating the utility of various non-invasive monitoring methods. The hypothesis of the project is that local inflammatory changes in the lung induced by allergen can be captured by gas-enhanced magnetic resonance imaging (MRI) and analysis of exhaled breath. The validation of cellular outcome measures and non-invasive inflammometry can be used in future clinical trials for proof of concept of novel anti-inflammatory medications. Participants will undergo

• methacholine challenge
• 2 inhaled allergen challenges
• 2 MRI with hyperpolarized xenon and gadolinium based contrast agent
• 2 bronchoscopies with bronchoalveolar lavage (BAL)
• segmental allergen challenge during the first bronchoscopy
• spirometry
• skin prick test and skin prick dilution tests
• measurement of particles in exhaled air
• nasal filter
• nasal lavage
• sputum induction
• peak flow meter tests
• exhaled NO (nictric oxide)
• blood sampling (in total approx. 190 ml)

Conditions

Mild Allergic Asthma

Outcome Measures

Primary Outcomes (6)

• Exploratory (1. priority) Changes in soluble mediators [i.e. IL-4, IL-5, IL-8, IL-13, IL-33, TSLP, IL-1, IL-6, INF-alpha, MMP-9, CXCL1, SP-D, albumin] in Bronchoalveolar lavage (BAL) after segmental allergen challenge

  Quantification of allergic inflammatory response induced by segmental allergen challenge in BAL by analyzing soluble mediators using Meso Scale Discovery (MSD) multiplex assays -\> At least, but not limited to Interleukin(IL)-4, IL-5, IL-8, IL-13, IL-33, Thymus-Stroma-Lymphopoietin (TSLP), IL-1, IL-6, Interferon-alpha (INF-alpha), Matrix-Metallopeptidase 9 (MMP-9), Chemokine (C-X-C motif) ligand 1 (CXCL1), Surfactant protein D (SP-D), albumin \[pg/ml\]

  24 hours after segmental allergen challenge

• Exploratory (1. priority) Changes in soluble mediators [i.e. IL-4, IL-5, IL-8, IL-13, IL-33, TSLP, IL-1, IL-6, NF-alpha, MMP-9, CXCL1, SP-D, albumin] in Sputum after inhalative allergen challenge

  Quantification of allergic inflammatory response induced by inhalation in sputum by analyzing soluble mediators using MSD multiplex assays -\> At least, but not limited to IL-4, IL-5, IL-8, IL-13, IL-33, TSLP, IL-1, IL-6, NF-alpha, MMP-9, CXCL1, SP-D, albumin \[pg/ml\]

  24 hours after segmental allergen challenge

• Exploratory (1. priority) Changes in non-invasive exhaled particles [i.e.IL-4, IL-5, IL-8, IL-13, IL-33, TSLP, IL-1, IL-6, NF-alpha, MMP-9, CXCL1, SP-D, albumin]after inhalative allergen challenge

  Quantification of allergic inflammatory response induced by inhalation in non-invasive exhaled particles at multiple time-points by analyzing soluble mediators using MSD multiplex assays -\> At least, but not limited to IL-4, IL-5, IL-8, IL-13, IL-33, TSLP, IL-1, IL-6, INF-alpha, MMP-9, CXCL1, SP-D, albumin \[pg/ml\]

  before, 3, 6 and 24 hours after inhaled allergen challenge

• Exploratory (1. priority) Changes in non-invasive exhaled particles [i.e.IL-4, IL-5, IL-8, IL-13, IL-33, TSLP, IL-1, IL-6, NF-alpha, MMP-9, CXCL1, SP-D, albumin]after segmental allergen challenge

  Quantification of allergic inflammatory response induced by segmental allergen challenge in non-invasive exhaled particles at multiple time-points by analyzing soluble mediators using MSD multiplex assays -\> At least, but not limited to IL-4, IL-5, IL-8, IL-13, IL-33, TSLP, IL-1, IL-6, INF-alpha, MMP-9, CXCL1, SP-D, albumin \[pg/ml\]

  before, 3, 6 and 24 hours after segmental allergen challenge

• Exploratory (1. priority) Changes in cell analyzation in BAL [i.e.total cells, neutrophil granulocytes, eosinophil granulocytes, basophil granulocytes, monocytes/macrophages, lymphocytes and dendritic cells] after segmental allergen challenge

  Quantification of allergic inflammatory response induced by segmental allergen challenge in BAL by analyzing cellularity and functionality using microscopy, flow cytometry and chipcytometry -\>At least, but not limited to total cells, neutrophil granulocytes, eosinophil granulocytes, basophil granulocytes, monocytes/macrophages, lymphocytes and dendritic cells \[×10\^6 cells/ml\]

  24 hours after segemental allergen challenge

• Exploratory (1. priority) Changes in cell analyzation in Sputum [i.e.total cells, neutrophil granulocytes, eosinophil granulocytes, basophil granulocytes, monocytes/macrophages, lymphocytes and dendritic cells] after inhalative allergen challenge

  Quantification of allergic inflammatory response induced by inhalation in sputum by analyzing cellularity and functionality using microscopy, flow cytometry and chipcytometry -\> At least, but not limited to total cells, neutrophil granulocytes, eosinophil granulocytes, basophil granulocytes, monocytes/macrophages, lymphocytes and dendritic cells \[×10\^6 cells/ml\]

  before, 6 and 24 hours after inhaled allergen challenge

Secondary Outcomes (4)

• Exploratory (2. priority) Detection of Ribonucleic acid (RNA) in exhaled particles

  before, 3, 6, and 24 hours after allergen challenge

• Exploratory (2. priority) Changes in Fractional exhaled nitric oxide (FeNO) after inhalative allergen challenge

  before, 3, 6, and 24 hours after inhaled allergen challenge

• Exploratory (2. priority) Changes in FeNO after segmental allergen challenge

  before, 3, 6 and 24 hours after segmental allergen challenge

• Exploratory (2. priority) Quantification of regional ventilation, perfusion, and diffusion by magnetic resonance imaging (MRI)

  before and 6 hours after inhaled allergen challenge

Study Arms (1)

single arm

OTHER

It is an exploratory study. All participants will undergo allergen challenge.

Other: allergen challenge

Interventions

allergen challenge OTHER

Patients will undergo inhaled allergen challenge followed by different measures like MRI and induced sputum. At least 4 weeks later patients will undergo segmental allergen challenge followed by different measures like bronchoalveolar lavage.

single arm

Eligibility Criteria

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

You may qualify if:

• Able and willing to give written informed consent.
• Not pregnant, as confirmed by pregnancy test (see assessment schedule), and not nursing.
• Of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarcheal 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 (vasectomised partner, sexual abstinence, implants, injectables, combined oral contraceptives, hormonal Intrauterine Devices (IUDs) or double-barrier methods, i.e. any double combination of IUD, condom with spermicidal gel, diaphragm, sponge, and cervical cap).
• History of mild asthma for at least 12 months prior to the Screening Visit that is well controlled with Short Acting Beta-Adrenergic Stimulator (SABA) only.
• Body mass index between 18 and 32 kg/m2
• Normal pulmonary function with forced Expiratory Volume in the first second (FEV1) ≥80% of predicted normal and FEV1/Forced Vital Capacity(FVC) ≥70% at Screening Visit. Calculations will be based on Global Lung Function Initiative (GLI) formula. If the participant fails to meet this criterion on the first measurement, spirometry may be repeated twice.
• Positive skin prick test (wheal diameter reaction ≥3 mm) for the respective challenge aeroallergen (i.e. tree, weed, grass or house dust mite) at or within 12 months prior to the Screening Visit (if performed and documented at Fraunhofer ITEM).
• Positive early and late asthmatic response upon incremental inhaled allergen challenge at or prior to the Screening Visit (if performed and documented at Fraunhofer ITEM).
• Production of adequate sputum with ≥1 x 106 total non-squamous cells at or within 12 month prior to the Screening Visit 1 (if not performed and documented at Fraunhofer ITEM).
• Nonsmokers with a history of less than 1 pack year having been nonsmokers for at least one year.

You may not qualify if:

• Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, urinalysis, vital signs, lung function or ECG at Screening Visit, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study or may influence the results of the study, or the subject's ability to participate in the study.
• Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, metabolic disease (asymptomatic Gilbert's syndrome is allowed), endocrine disease (stable and asymptomatic hypothyroidism with or without hormone replacement therapy (HRT) is allowed), or pulmonary disease (including but not confined to chronic bronchitis, emphysema, tuberculosis, bronchiectasis or cystic fibrosis).
• Regular intake of any prescribed or over the counter medication. Exceptions include paracetamol for pain relief, contraceptive medication, hormonal replacement therapy, dietary and vitamin supplements.
• Specific Immunotherapy (SIT) within three years prior to the study.
• Intake of systemic or inhaled steroids within 4 weeks before Screening Visit 1a.
• Respiratory tract infection (RTI) within 4 weeks before Screening Visit 1a.
• Mild to moderate asthma exacerbation within 3 months before Screening Visit 1a.
• Any history of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures.
• Suspected hypersensitivity to any ingredients of the medication in line with bronchoscopy (bronchodilators, sedatives and local anesthetics).
• Conditions or factors, which would make the subject unlikely to be able to undergo bronchoscopy or allergen challenge.
• Conditions or factors, which would make the subject unlikely to undergo MRI (e.g. due to claustrophobia, cardiac pacemaker, hypersensitivity to MR i.v. contrast imaging agents).
• Participation in another clinical trial with Investigational Medicinal Product (IMP) 30 days or 5 half-lives, whichever is longer, prior to enrollment.
• Participation in the observation period of a competing study within 30 days prior to Screening.
• Segmental allergen challenge three months prior to bronchoscopy.
• Donation of more than 400 ml of blood the preceding 60 days before screening.

Sponsors & Collaborators

• Fraunhofer-Institute of Toxicology and Experimental Medicine: lead

Study Sites (1)

Fraunhofer Institute for Toxicology and Experimental Medicine

Hanover, Lower Saxony, 30625, Germany

RECRUITING

Central Study Contacts

Jens Hohlfeld, Prof. Dr.

CONTACT

+49 511 5350-8101; jens.hohlfeld@item.fraunhofer.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2024
• First Posted: March 19, 2024
• Study Start: August 9, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)