Prednisolone Pharmacokinetics in Severe Asthma - Full Text View

Sponsors and Collaborators:	Imperial College London Royal Brompton Hospital NHS Trust
Information provided by:	Imperial College London
ClinicalTrials.gov Identifier:	NCT00662298

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

to compare the effect of high dose prednisolone on clinical and physiological responses
to determine the effect of long-term oral prednisolone therapy on corticosteroid responsiveness and prednisolone pharmacokinetics
to measure the effect of high dose prednisolone for 14 days on p38 MAPK activity, GR translocation and activation of NF-kB
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 IV

MedlinePlus related topics: Asthma

Drug Information available for: Prednisolone 6-Methylprednisolone Depo-medrol Medrol veriderm Methylprednisolone Methylprednisolone hemisuccinate Methylprednisolone Sodium Succinate Prednisolone acetate Prednisolone sodium phosphate Prednisolone Sodium Succinate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Non-Randomized, Open Label, Single Group Assignment, Pharmacokinetics/Dynamics Study
Official Title:	The Pharmacokinetics and Anti-Inflammatory Effects of Prednisolone in Severe Asthma

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:	October 2008
Estimated Study Completion Date:	February 2012
Estimated Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Intervention Details:

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

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 Hospital NHS Trust

Investigators

Principal Investigator:

Kian F Chung

Imperial College London

More Information

Responsible Party:	Imperial College London ( Professor Kian Fan Chung )
Study ID Numbers:	2007-002084-27, REC ref number 07/H0801/119
Study First Received:	April 14, 2008
Last Updated:	October 21, 2008
ClinicalTrials.gov Identifier:	NCT00662298
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

Study placed in the following topic categories:

Hypersensitivity
Lung Diseases, Obstructive
Respiratory Tract Diseases
Methylprednisolone
Lung Diseases
Prednisolone

Hypersensitivity, Immediate
Methylprednisolone acetate
Asthma
Prednisolone acetate
Methylprednisolone Hemisuccinate
Respiratory Hypersensitivity

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Bronchial Diseases
Immune System Diseases
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics

Protective Agents
Neuroprotective Agents
Glucocorticoids
Hormones
Pharmacologic Actions
Autonomic Agents
Therapeutic Uses
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009