Prednisolone Pharmacokinetics in Severe Asthma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Imperial College London.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Royal Brompton & Harefield NHS Foundation Trust
Information provided by:
Imperial College London
ClinicalTrials.gov Identifier:
NCT00662298
First received: April 14, 2008
Last updated: June 22, 2011
Last verified: June 2011
  Purpose

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

Condition Intervention Phase
Asthma
Drug: prednisolone
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: The Pharmacokinetics and Anti-inflammatory Effects of Prednisolone in Severe Asthma

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • serum prednisolone levels over 24 hours [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • change in FEV1 24 hours post prednisolone [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • changes in eNO, sputum eosinophils and inflammatory mediators over 24 hours [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • difference between day 1 and day 14 in serum prednisolone levels [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • difference in FEV1 between day 1 and day 14 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • difference in inflammatory markers between day 1 and day 14 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • changes in asthma control symptoms before and after treatment [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: June 2011
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: prednisolone
    40mg of prednisolone once a day for 14 days
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00662298

Contacts
Contact: Patricia Macedo 02-07-351-8051 p.macedo@imperial.ac.uk
Contact: Florence Chow 02-07-351-8051 florence.chow@imperial.ac.uk

Locations
United Kingdom
Asthma Laboratory, Royal Brompton Hospital Recruiting
London, United Kingdom, SW3 6LY
Sub-Investigator: Patricia Macedo, MBBS MRCP MSc         
Principal Investigator: Kian F Chung, MBBS MD FRCP DSc         
Sponsors and Collaborators
Imperial College London
Royal Brompton & Harefield NHS Foundation Trust
Investigators
Principal Investigator: Kian F Chung Imperial College London
  More Information

No publications provided

Responsible Party: Professor Kian Fan Chung, Imperial College London
ClinicalTrials.gov Identifier: NCT00662298     History of Changes
Other Study ID Numbers: 2007-002084-27, REC ref number 07/H0801/119
Study First Received: April 14, 2008
Last Updated: June 22, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
severe asthma
prednisolone pharmacokinetics
anti-inflammatory effects

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases
Anti-Inflammatory Agents
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014