Prednisolone Pharmacokinetics in Severe Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: prednisolone
Intervention description: 40mg of prednisolone once a day for 14 days
Intervention MeSH terms: Prednisolone
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: severe asthma; prednisolone pharmacokinetics; anti-inflammatory effects

Summary:

      The purpose of the study is to evaluate whether severe asthmatic subjects have abnormal
      prednisolone absorption, and how this might affect the anti-inflammatory effects of
      prednisolone.

      The aims of the study are

        1. to compare the effect of high dose prednisolone on clinical and physiological responses

        2. to determine the effect of long-term oral prednisolone therapy on corticosteroid
           responsiveness and prednisolone pharmacokinetics

        3. to measure the effect of high dose prednisolone for 14 days on p38 MAPK activity, GR
           translocation and activation of NF-kB

        4. to validate an easier method of measuring corticosteroid insensitivity using whole
           blood, and a spot prednisolone serum level as a measure of adherence to prednisolone
           therapy
    

Eligibility criteria:

        Inclusion Criteria:

          -  for severe asthmatics:

               -  Physician diagnosis of asthma

               -  Aged 18 - 70

               -  Non-smokers or ex-smokers with less than 5 pack/year history

               -  Major characteristics (at least one of the following criteria)

               -  Treatment with continuous or near continuous (>50% of year) oral corticosteroids

               -  Requirement for treatment with high dose inhaled corticosteroids (ICS)

               -  Minor characteristics (at least 2 out of the following)

                    1. Requirement for daily treatment with a controller medication in addition to
                       ICS e.g. LABA, theophylline, leukotriene antagonist

                    2. Asthma symptoms requiring SABA on a daily or near daily basis

                    3. Persistent airways obstruction (FEV1 <80% predicted, diurnal PEF variation
                       >20%)

                    4. One or more emergency care visits for asthma per year

                    5. 3 or more steroid "bursts" per year

                    6. Prompt deterioration with ≤ 25% reduction in oral or ICS

                    7. Near fatal asthma event in the past

          -  for moderately-severe asthma:

               -  Physician diagnosis of asthma

               -  Aged 18 - 70

               -  Non-smokers or ex-smokers with less than 5 pack/year history

               -  Less than 2 courses of prednisolone per year

               -  Taking up to 2000 mcg of inhaled corticosteroid (BDP equivalent) per day

               -  Stable asthma for at least 6 months prior to enrollment

        Exclusion Criteria:

          -  Current smokers, or less than 3 years since quitting smoking

          -  Less than 4 weeks from an exacerbation

          -  Diabetes

          -  Active peptic ulceration

          -  Previous history of psychiatric disturbances on high dose prednisolone

          -  On steroid-sparing agent or immunosuppressant such as azathioprine, methotrexate and
             ciclosporin

          -  Concomitant anti-IgE therapy

          -  Pregnancy