Mannitol-Induced Cough Challenge in Healthy Controls and Subjects With Mild Allergic Asthma
Condition: Asthma; Cough
MeSH terms: Asthma; Cough
Study type: Interventional

Summary: 
      The study aim is to investigate if changes in osmolarity using mannitol challenge can evoke
      coughing reproducibly in mild allergic asthmatics compared with healthy controls and if
      salbutamol can affect this. Phase 1 of this study is a reproducibility analysis of cough dose
      response to mannitol in a cohort of mild allergic asthmatics and healthy controls. Phase 2 is
      a double-blind, placebo-controlled analysis in mild allergic asthmatics assessing the effects
      of salbutamol on mannitol induced cough.
    

Detailed description: 
      The study will have a maximum of 4 visits separated by at least 24 hours. The first 2 visits
      will determine eligibility. All eligible subjects will be invited back for a third visit, and
      only subjects with mild allergic asthma will be invited back for a fourth visit.

      Screening Period (Visits 1 and 2) - For All Subjects Eligible subjects will be identified
      during the initial screening procedures with measures of spirometry, hyperresponsiveness to
      methacholine, complete history, physical examination, allergen skin test, and mannitol cough
      challenge. The screening procedures will be conducted over 2 separate visits.

      Reproducibility (Visit 3) - For Healthy Controls Ten normal healthy controls meeting study
      eligibility will return for visit 3. This visit must be at least 24h after the mannitol test
      at visit 1. These data will be used for assessing reproducibility of the mannitol induced
      coughs; Emax and the median effective dose (ED50).

      Effects of Salbutamol (Visit 3 and 4) - For Mild Allergic Asthma Subjects Ten subjects with
      mild allergic asthma will return for visit 3 and 4. These visits must be at least 24h apart
      and no longer than 7 days. Mild allergic asthmatics will first receive salbutamol 2.5mg or
      saline placebo via a nebuliser and 15 mins later the forced expiratory volume at one second
      (FEV1) measured. Subjects will then undergo a mannitol cough challenge exactly like the
      previous mannitol cough challenges. These data will be used for determining the effects of
      salbutamol on mannitol-induced bronchoconstriction and cough.

      Visit Windows Each visit must be separated by a minimum of 24 hours, and a maximum of 7 days.
      Study visits can be performed in the morning or afternoon, however for each subject the
      timing should be consistent with Visits 2 at the same time of day ± 2 hours
    

Intervention name(s): Mannitol; Salbutamol 5mg/mL; Sodium Chloride 0.9% Inhl 3Ml
Intervention type(s): Other; Drug; Other
Intervention description(s): Mannitol-Induced Cough Challenge; Nebulized salbutamol given prior to Mannitol-Induced Cough Challenge; Nebulized 0.9% saline given prior to Mannitol-Induced Cough Challenge
Other intervention name(s): Aridol; Active Comparator; Placebo Comparator
Intervention MeSH terms: Mannitol; Albuterol
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a mechanistic study. The first part of the study (mild allergic asthmatics and healthy controls) is to determine reproducibility of dose responses to mannitol-induced coughs. The second part of the study (mild asthmatics only) is to determine the effect of salbutamol on mannitol-induced coughs. Salbutamol or placebo will be delivered following a mannitol cough challenge in a randomized, double-blind crossover design.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Mannitol; Bronchoconstriction; Airway nerve function; Cough; Diagnostic Test; Osmolarity; Salbutamol