Rosiglitazone Versus Theophylline in Asthmatic Smokers
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Asthmatic smokers display a blunted response to both inhaled and oral corticosteroid
      treatments and are at increased risk for exacerbations and near fatal asthma. The prevalence
      of smoking in asthmatics runs between 20-30%. Therefore, new, more efficacious treatments are
      required.

      Recent work has demonstrated a mechanism which may explain steroid resistance. A commonly
      used drug called theophylline can reverse this steroid resistance in laboratory studies.
      Another commonly used drug, rosiglitazone can reverse smoking induced lung inflammation in
      laboratory studies.

      The investigators aim to study the effects of these drugs on smoking asthmatics' lung
      function and other parameters including quality of life and asthma control.
    

Detailed description: 
      Smoking asthmatics have chronic pulmonary inflammation that is relatively steroid resistant.
      PPAR agonists (of which rosiglitazone is one example) have been shown to reduce several
      markers of inflammation in humans and in smoking animal models.

      This clinical study will use smoking asthmatics as a human model of smoke-induced
      steroid-insensitive airway inflammation to evaluate both efficacy of rosiglitazone as an
      anti-inflammatory drug as well as the effect of low doses of theophylline on the response to
      low-dose inhaled corticosteroid (LD ICS).

      Mild or moderate (as per GINA guidelines) persistent-asthmatic smokers will be randomised
      into this study after a 4-week washout period during which they will be withdrawn from
      inhaled corticosteroids (ICS). Subjects will then receive one of four treatments for 28 days:
      rosiglitazone, LD ICS, theophylline, or LD ICS plus theophylline.

      The effects of rosiglitazone and LD ICS on pulmonary function will be compared as a primary
      objective. In addition, effects of theophylline plus LD ICS will be compared against
      theophylline and LD ICS separately. Both pulmonary anti-inflammatory and systemic
      anti-inflammatory activity will also be investigated.

      Subjects will have baseline assessments of pulmonary function, biomarkers of systemic
      inflammation, sputum, exhaled breath biomarkers, asthma control questionnaires and safety
      parameters. Following 28 days of treatment, these parameters will all be reassessed in all
      subjects.
    

Intervention name(s): rosiglitazone; theophylline; beclomethasone; inhaled beclomethasone and oral theophylline
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): oral tablet, 4mg bd for 4 weeks; Oral theophylline, 200mg bd; inhaled beclomethasone, 200mcg bd; inhaled beclomethasone (400mcg/day), oral theophylline (400mg/day)
Other intervention name(s): Rosiglitazone Maleate, Avandia; uniphyllin; Qvar; Qvar and uniphyllin
Intervention MeSH terms: Rosiglitazone; Beclomethasone; Theophylline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Corticosteroid; Rosiglitazone; Theophylline; Beclomethasone; Inflammation; Asthma; Smoking; Pulmonary