Corticosteroids/β2-agonists in Hair in Asthmatic Patients (CorticHair)

Not Applicable

• Conditions: Asthma
• Interventions: Other: Hair sampling; Diagnostic Test: Hair's drug concentrations

• Registration Number: NCT03691961
• Lead Sponsor: Hopital Foch

Brief Summary

This feasibility study will be open-label with two dose groups: patients receiving budesonide/formoterol Turbuhaler® at a total daily dose \[400 to 800 µg\[ (group 1) and patients receiving a total daily dose ≥800 µg/day (group 2) to investigate whether there is a relationship between dose and hair concentration.

The objective of this feasibility study is to determine if the product administered to the patient is detectable and quantifiable in hair in order to have a mean to monitor adherence to the treatment. This study does not in any way evaluate the efficacy or safety of the medicinal product, which will be used in accordance with its marketing authorization.

Detailed Description

Asthma affects 3-10% of the European population and is a heterogeneous disease in its clinical manifestations and also in its response to treatment. Since therapy is often started at young age and given over many years, with adjustments made on disease control, long-term adherence and efficacy are particular concerns.

Adherence to inhaled controller medications is a major challenge to obtain disease control and to avoid serious asthma flare-ups or unnecessary treatment stepping up. In addition to adherence concerns, poor asthma control may also be the consequence of a poor inhalation technique and the resulting insufficient drug exposure.

To overcome adherence issues, patients are encouraged to self-manage their disease and the use of new technologies such as inhaler reminders, electronic devices and/or smartphone applications may be helpful. Although there is a margin to improve and monitor adherence, assessing the efficiency of the inhalation technique in daily routine and its consequences in terms of drug exposure is much harder.

The traditional monitoring of pharmacological therapies involves therapeutic drug monitoring, i.e. the measure of drug concentration in plasma. But drugs concentration in plasma most only reflect the quantity of drug in the body in the last 24-48 hrs only. Hence, therapeutic drug monitoring is not used for inhaled asthma treatments, in part because of the limited interest in assessing only a 24-48 hrs exposure and of the very low plasma concentrations which are very challenging to measure.

Since drugs present in the bloodstream also reach and stay in the forming hair where their concentrations can be measured and interpreted as an overall chronic exposure, hair analysis could become a valuable tool in the monitoring of inhaled asthma treatments, with the use of very specific mass spectrometry techniques and of the most sensitive last-generation mass spectrometers.

Study Timeline

• Study Start: 2018-09-20
• Study First Submitted: 2018-09-28
• Study First Submitted QC: 2018-10-01
• Study First Posted: 2018-10-02
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-02
• Last Update Posted: 2022-08-03
• Primary Completion: 2023-07-20
• Study Completion: 2023-07-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Provision of informed consent prior to any study specific procedure
• Outpatients with asthma, of either gender, aged ≥18 and <50 years at visit 1
• Controlled or partly controlled asthma according to the Global Initiative for Asthma (GINA) guideline
• Receiving a constant daily dose ≥400 µg budesonide of budesonide/formoterol Turbuhaler® for more than 2 months
• No treatment step-down is planned in the 3 next months
• ACQ (Asthma Control Questionnaire) score ≤ 1.50
• Patient with healthcare insurance

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Exclusion Criteria

• Pregnant women or women wishing to become pregnant in the next 3 months
• Patients with body mass index (BMI) <18 or >30
• Patients with known kidney or liver disease (creatinine clearance < 60 mL/min/1.73 m² or alanine aminotransferase (ALAT) > 5N)
• Smokers or former smokers < 3 years
• Patients with simultaneous asthma and chronic obstructive pulmonary disease (COPD) (or defined as having asthma-COPD overlap syndrome)
• Other budesonide- or formoterol-containing drugs (e.g Foradil®, Rhinocort®, Mikicort®, Entocort®...)
• CYP3A4 inducers (systemic corticosteroid, rifampicin, phenobarbital, carbamazepine...)
• CYP3A4 inhibitors (macrolides, azole antifungals, valproic acid, amiodarone, fluoxetine)
• Hair treatment (coloration, bleaching, perming...)
• Hairless patients, hair implants or hair extensions
• Length of hair from the vertex posterior region < 5 cm or planning to cut hair from this region shorter than 5 cm in the next 4 months
• Patient deprived of liberty by judicial or administrative decision
• Major protected by law

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High dose of Symbicort Turbuhaler®	Hair's drug concentrations	The population is asthmatic patients meeting the inclusion and exclusion criteria for whom the optimized total daily dose to treat the disease is ≥800 µg budesonide of budesonide/formoterol Symbicort TurbuhalerTurbuhaler®. Hair sampling after 4 months treatment. Analysis of hair's drug concentrations.
High dose of Symbicort Turbuhaler®	Hair sampling	The population is asthmatic patients meeting the inclusion and exclusion criteria for whom the optimized total daily dose to treat the disease is ≥800 µg budesonide of budesonide/formoterol Symbicort TurbuhalerTurbuhaler®. Hair sampling after 4 months treatment. Analysis of hair's drug concentrations.
Medium dose of Symbicort Turbuhaler®	Hair sampling	The population is asthmatic patients meeting the inclusion and exclusion criteria for whom the optimized total daily dose to treat the disease is ≥400 to 800 µg budesonide of budesonide/formoterol Symbicort Turbuhaler®. Hair sampling after 4 months treatment. Analysis of hair's drug concentrations.
Medium dose of Symbicort Turbuhaler®	Hair's drug concentrations	The population is asthmatic patients meeting the inclusion and exclusion criteria for whom the optimized total daily dose to treat the disease is ≥400 to 800 µg budesonide of budesonide/formoterol Symbicort Turbuhaler®. Hair sampling after 4 months treatment. Analysis of hair's drug concentrations.

Primary Outcome Measures

Name	Time	Method
Budesonide/formoterol hair concentrations (active substance and metabolites)	4 months	After 4 months of treatment, the hair's concentrations of budesonide/formoterol is analyzed with mass spectrometry.

Secondary Outcome Measures

Name	Time	Method
Budesonide/formoterol hair's concentration compared to the daily observance.	4 months	Patient cumulative dose is estimated from daily observance recorded by the patient in the observance record.
Correlation between budesonide/formoterol hair concentrations, forced expiratory volume in 1 second (FEV1), and asthma control questionnaire (ACQ)	4 months	FEV1 (measured according to a standardized spirometry technique), and ACQ (patients with a score below 1.0 will have adequately controlled asthma and above 1.0 their asthma will not be well controlled) are collected at the inclusion visit and the 4 months visit
Budesonide/formoterol concentration in three 1-cm hair segments (active substance and metabolites)	4 months	After 4 months of treatment, the concentrations of budesonide/formoterol in three 1-cm hair segments is analyzed with mass spectrometry.

Trial Locations

Locations (1)

Foch Hospital; 🇫🇷 Suresnes, France