Non-invasive monitoring of airway inflammation in mild allergic asthma

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

This study is testing new ways to monitor lung inflammation in people with mild allergic asthma after exposure to allergens to see if these methods can help in future treatments.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Fraunhofer-Institute of Toxicology and Experimental Medicine (Academic / other)
• Drugs / interventions: Immunotherapy
• Locations: 1 site (Hanover, Lower Saxony)
• Trial ID: NCT06317909 on ClinicalTrials.gov

What this trial studies

This exploratory study aims to develop and evaluate novel non-invasive methods for monitoring airway inflammation in patients with mild allergic asthma following allergen challenges. Participants will undergo a series of tests including methacholine challenges, inhaled allergen challenges, and magnetic resonance imaging (MRI) using hyperpolarized xenon and gadolinium-based contrast agents. The study seeks to validate these non-invasive techniques to capture local inflammatory changes in the lungs, which could be beneficial for future clinical trials of anti-inflammatory medications. The entire participation period spans approximately 6 to 8 weeks, involving multiple visits to the Fraunhofer Institute in Hannover.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with a history of mild asthma who can provide informed consent.

Not a fit: Patients with severe asthma or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved methods for monitoring airway inflammation in asthma patients, potentially enhancing treatment strategies.

How similar studies have performed: While the approach of using non-invasive monitoring methods is innovative, similar studies have shown promise in capturing airway inflammation, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

1. Able and willing to give written informed consent.
2. Male and female subjects aged 18-65 years. Women will be considered for inclusion if they are:

   * 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).
3. 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.
4. Body mass index between 18 and 32 kg/m2
5. 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.
6. 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).
7. 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).
8. 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).
9. Nonsmokers with a history of less than 1 pack year having been nonsmokers for at least one year.

Exclusion Criteria:

1. 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.
2. 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).
3. 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.
4. Specific Immunotherapy (SIT) within three years prior to the study.
5. Intake of systemic or inhaled steroids within 4 weeks before Screening Visit 1a.
6. Respiratory tract infection (RTI) within 4 weeks before Screening Visit 1a.
7. Mild to moderate asthma exacerbation within 3 months before Screening Visit 1a.
8. 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.
9. Suspected hypersensitivity to any ingredients of the medication in line with bronchoscopy (bronchodilators, sedatives and local anesthetics).
10. Conditions or factors, which would make the subject unlikely to be able to undergo bronchoscopy or allergen challenge.
11. 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).
12. Participation in another clinical trial with Investigational Medicinal Product (IMP) 30 days or 5 half-lives, whichever is longer, prior to enrollment.
13. Participation in the observation period of a competing study within 30 days prior to Screening.
14. Segmental allergen challenge three months prior to bronchoscopy.
15. Donation of more than 400 ml of blood the preceding 60 days before screening.
16. History of regular drug or alcohol abuse
17. Risk of non-compliance with study procedures.
18. Suspected inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study.

Where this trial is running

Hanover, Lower Saxony

• Fraunhofer Institute for Toxicology and Experimental Medicine — Hanover, Lower Saxony, Germany (Recruiting)

Study contacts

• Study coordinator: Jens Hohlfeld, Prof. Dr.

Conditions Mild Allergic Asthma