Mild Allergic Asthma Clinical Trial
Official title:
Development of a Novel Non-invasive Inflammometry Following Allergen Challenge in Patients With Mild Allergic Asthma
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)
An individual study participation takes about 6 to 8 weeks for the experimental phase not including a screening phase that can add up to 8 weeks. The study consists of 10 visits. All visits take place at Fraunhofer ITEM in Hannover. During screening an inhaled allergen challenge will be performed to decide about eligibility. During the experimental part another inhaled allergen challenge, 2 magnetic resonance imaging (MRI) and 2 bronchoscopies with segmental allergen challenge will be performed. Methacholine Challenge: The methacholine bronchial challenge will be performed in accordance with study sites Standard Operating Procedure (SOP). Methacholine will be used according to the manufacturers' instruction. After an initial saline inhalation as a reference, the percent decrease in Forced Expiratory Volume in the first second (FEV1) after each succeeding concentration of methacholine will be determined until the FEV1 drops to 80% of the reference value. An interpolated PC20 (aerosol concentration of methacholine leading to a 20% fall in the FEV1) will be calculated. Inhaled allergen challenge: For the inhaled allergen challenge the allergen most likely to induce allergic airway responses will be selected during the screening period. The allergens used for provocation in this study will be lyophilized allergen extracts of respective allergen (LETI Laboratories) developed and licensed for provocation testing. The starting concentration of allergen extract to be given by inhalation will be calculated based on the prick dilution test as well as the methacholine challenge in order to obtain the allergen concentration that is predicted to cause a 20% decrease in FEV1 ( PC20). Bronchoscopies with BAL and segmental allergen challenge: Bronchoscopy will be performed according to the study sites which is consistent with international recommendations for fiberoptic bronchoscopy. In this clinical investigation, two bronchoscopies will be conducted under identical conditions 24 hours apart. Before instillation of allergen, a baseline lavage will be performed during the first bronchoscopy. . Thereafter, a control challenge will be performed by injecting 10 ml of 37°C sterile 0.9% saline.During the second bronchoscopy after 24 hours, BAL from the two challenged segments will be collected. The allergen used for inhaled provocation will be used for segmental provocation as well. Magnetic resonance imaging: MRI will be performed at the Clinical Research Center by the Institute for Radiology using a Siemens Avanto 1.5T scanner. In order to assess local inflammation by proton MRI, various sequences will be applied during the imaging session. In addition, gas-enhanced protocols with hyperpolarized xenon will be applied according to the study sites SOP. For the assessment of pulmonary perfusion, a gadolinium based contrast agent (Gadopentetat - Dimeglumin) will be given iv during each MRI scan. It will be 1/3 of the regular dose for this contrast agent. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01092403 -
Safety, Tolerability and Clinical Activity of ASM-024 in Subjects With Mild Allergic Asthma
|
Phase 2 |