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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Therapeutic Drug Monitoring of Corticosteroids/β2-agonists in Hair in Asthmatic Patients: an Open-label Feasibility Study

Conditions
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Asthma

Intervention / Treatment
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* Other: Hair sampling
* Diagnostic Test: Hair's drug concentrations


Participation Criteria
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Eligibility Criteria
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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 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Half of the patients is enrolled in each group according to the individual dose decided by the clinician in charge as the optimal dose to treat the disease. The optimized dose to treat the disease is decided independently of the participation to the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medium dose of Symbicort Turbuhaler®<br>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. | Other: Hair sampling<br>* After 4 months of treatment, a strand of hair from the vertex posterior region of the scalp about the width of a thin pencil and with a length equal to or greater than 3 cm will be cut.<br>Diagnostic Test: Hair's drug concentrations<br>* The hair's concentrations of budesonide/formoterol is analysed with mass spectrometry.<br>|
| Experimental: High dose of Symbicort Turbuhaler®<br>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. | Other: Hair sampling<br>* After 4 months of treatment, a strand of hair from the vertex posterior region of the scalp about the width of a thin pencil and with a length equal to or greater than 3 cm will be cut.<br>Diagnostic Test: Hair's drug concentrations<br>* The hair's concentrations of budesonide/formoterol is analysed with mass spectrometry.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Budesonide/formoterol hair concentrations (active substance and metabolites) | After 4 months of treatment, the hair's concentrations of budesonide/formoterol is analyzed with mass spectrometry. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Budesonide/formoterol concentration in three 1-cm hair segments (active substance and metabolites) | After 4 months of treatment, the concentrations of budesonide/formoterol in three 1-cm hair segments is analyzed with mass spectrometry. | 4 months | 
| Budesonide/formoterol hair's concentration compared to the daily observance. | Patient cumulative dose is estimated from daily observance recorded by the patient in the observance record. | 4 months | 
| Correlation between budesonide/formoterol hair concentrations, forced expiratory volume in 1 second (FEV1), and asthma control questionnaire (ACQ) | 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 | 4 months |