Investigation to Identify Predictors of Response to a Treatment With Montelukast
Condition: Asthma
Study type: Interventional
Phase: Phase 4

Summary: 
      The main aim of the study is to develop a method that allows responders to be distinguished
      from non-responders before long-term treatment is initiated. Subsidiary aims are to record
      changes in pulmonary functional parameters, NO concentrations and peak flow variability, the
      use of beta2 sympathomimetics and the asthma symptom score.
    

Detailed description: 
      Leukotriene antagonists (montelukast) are particularly effective as controllers before
      exposure to an allergen (Leff 1998). The same applies to the treatment of bronchoconstriction
      induced by physical exertion or cold air (Richter 2000). Montelukast binds to the cysteinyl
      leuko¬triene-1 receptor, where it prevents leukotriene from binding. Leukotrienes play a key
      role as mediators in inflammatory processes. By binding to the receptor they cause, among
      other things, edema, damage to the bronchial epithelium and bronchoconstriction. Accordingly,
      in addition to its anti-inflammatory activity montelukast brings about bronchial dilation.
      The safety and efficacy of the drug in children have been well documented (Knorr 1998). Hence
      montelukast is approved for the treatment of bronchial asthma in children (over six months of
      age). As with other antiasthmatic drugs, there are responders and nonresponders to
      leukotriene receptor antagonists. The proportion of nonresponders to montelukast among
      children is esti¬mated to be 30% to 40%. At present the only way to distinguish
      non-responders from responders is to run a treatment trial for several weeks. If the symptom
      score falls, if the use of beta2 sympathomimetics is reduced, if pulmonary function and/or
      the quality of life improves, it is assumed that the patient is a responder. This method is
      not only tedious but also unsafe, since a change is the aforementioned parameters could occur
      spontaneously, without this being reliably attributable to the influence of the drug. In the
      planned study approximately 30 children with asthma of GINA classes 2 and 3 will be regularly
      examined for pulmonary function, symptom score and nitrogen monoxide (NO). First, however,
      the acute pharmacologic effect of a single dose of montelukast will be deter¬mined over a
      period of four hours by measuring pulmonary function and levels of exhaled nitrogen monoxide
      (NO).

      4.2.1. Questions addressed:

      Is it possible to discriminate between responders and nonresponders at a very early stage on
      the basis of the acute pharmacologic effect of montelukast? Does this classification agree
      with the results after 12 weeks of treatment?

      4.2.2. Hypothesis:

      Patients who show a bronchospasmolytic effect in their functional pulmonary test (FEV1
      increased by at least 5%) within four hours of taking montelukast also show a positive
      response (defined as a combination of at least two variables (see section on the definition
      of responders/non-responders during treatment)) after 12 weeks of treatment. Conversely,
      patients who show no acute effect do not have a positive response during long-term therapy.

      In other words, the results of the acute pharmacologic effect correspond to the effect during
      long-term therapy.

      5. Aim of the study:

      The main aim of the study is to develop a method that allows responders to be distinguished
      from non-responders before long-term treatment is initiated. Subsidiary aims are to record
      changes in pulmonary functional parameters, NO concentrations and peak flow variability, the
      use of beta2 sympathomimetics and the asthma symptom score.

      6. Patient selection:

      The study will include approximately 30 patients aged 6 to 14 years with diagnosed bronchial
      asthma who have been on constant anti-inflammatory therapy for at least four weeks (GINA
      classes 2 and 3).

      7. Study design:

      This investigation is a single-center, two-phase, single-arm study. In order to detect a
      potential placebo effect, the treatment phase will be preceded by a single-blinded two-week
      placebo run-in phase, followed by a 12 week open-label treatment phase.
    

Intervention name(s): montelukast
Intervention type(s): Drug
Intervention description(s): 5mg montelukast once daily for 12 weeks
Other intervention name(s): Singulair ; MK-476
Intervention MeSH terms: Montelukast
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: responder; leucotriene antagonist