Prednisolone Pharmacokinetics in Severe Asthma

• Status: Completed
• Trial end date: 2013-01-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Imperial College London
• Collaborator: Royal Brompton & Harefield NHS Foundation Trust
• Treatments: Anti-Inflammatory Agents; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

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