The Use of FKBP51 in the Identification of Non-adherence to Inhaled Corticosteroids in Difficult Asthma

Approximately 5-10% of people with asthma do not respond to to standard therapy and are referred to as having difficult asthma. Evidence shows that this poor response is not always related to asthma severity and non-adherence to treatment is recognized as a common underlying problem, in 35% of these patients. Recognising non-adherence in the clinic is problematic as there is no straightforward objective test to identify it.

Previous studies have demonstrated up-regulation of FKBP51 gene expression following treatment with steroids, making it a potential biomarker of steroid exposure. It is therefore also a potential biomarker of non-adherence to inhaled corticosteroid therapy. The investigators plan to assess the feasibility of distinguishing non-adherent subjects who are by omission steroid naïve from adherent subjects, steroid exposed subjects using FKBP51 gene expression in sputum and throat swabs.

To do this the investigators will obtain throat swab and sputum samples from healthy volunteers, steroid naïve asthmatics and adherent asthmatics on high dose ICS to assess if FKBP51 gene expression is comparable in each group.

The investigators will then compare the FKBP51 gene expression response to directly observed inhaled steroid therapy in steroid naïve, non-adherent and adherent asthmatics. This will identify if the response in gene expression distinguishes steroid exposed (adherent) from steroid naïve (non-adherent) patients.

Identifying non-adherence will benefit patients by enabling appropriate tailored management for non-adherence to enhance treatment effectiveness. It will also identify patients with therapy resistant asthma who have an unmet need and may benefit from expensive novel therapies such as Omalizumab.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: inhaled steroid

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Belfast City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

This pilot study will investigate the following groups (n=10 per group):

1. Healthy volunteers.
2. Steroid naïve asthmatics.
3. Refractory asthmatics adherent to high dose inhaled steroids.
4. Non-adherent asthmatics.

Inclusion Criteria

For inclusion into this study all participants must:

• be 16 years old or older
• give written informed consent

Healthy volunteers must:

• be in good general health as determined by past medical history and physical.
• have no other significant medical history and specifically no prior history of asthma or persistent respiratory symptoms.
• normal spirometry.

Steroid naïve subjects

• have a diagnosis of asthma
• receiving treatment at Step 1 BTS/SIGN Guidelines i.e. no inhaled steroid

Non-adherent subjects must

• have a diagnosis of asthma
• be non-adherent to ICS as determined by ICS prescription filling of </=50% in the previous 6 months

Refractory asthmatic adherent subjects must:

• have a diagnosis of asthma receiving high dose ICS treatment (beclomethasone equivalent dose > 1000 µg per day)
• be adherent to ICS as determined by ICS prescription filling >75% in the previous 6 months

Exclusion Criteria:

Participants who fulfill the following criteria will be excluded from study entry:

• Current smoker,
• Pregnant or lactating,
• Other significant respiratory disease
• Previous allergic reaction or known hypersensitivity to budesonide or any corticosteroid

Healthy volunteers will be excluded if they have / are :

• any significant medical history which the principal investigator (PI) deems appropriate to be excluded from the healthy control group
• obstructive lung function
• taking any medication
• a current or history of drug or alcohol abuse
• any significant illness during the screening period preceding entry into the study

Steroid naïve / Non-adherent asthmatics will be excluded if they have:

• commenced or increase of oral corticosteroids in the previous 28 days
• a concurrent asthma exacerbation

Refractory / Adherent asthmatics will be excluded if they have:

• commenced or increased of oral corticosteroids in the previous 28 days
• a concurrent asthma exacerbation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: inhaled steroid; inhaled steroid treatment for 7 days	Drug: inhaled steroid; inhaled budesonide for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in FKBP51 gene expression	7 days

Collaborators and Investigators

• Sponsor: Liam Heaney
• Collaborators: Northern Ireland Chest Heart and Stroke

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: February 1, 2012
• First Submitted That Met QC Criteria: February 2, 2012
• First Posted (Estimate): February 6, 2012

Study Record Updates

• Last Update Posted (Estimate): October 10, 2014
• Last Update Submitted That Met QC Criteria: October 8, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: To identify changes in FKBP51 expression with inhaled steroid treatment in asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 10174LH-AS (Other Identifier: Belfast Health & Social Care Trust); 11/NI/0015 (Other Identifier: Regional Ethics Committee Northern Ireland)