A Cross-sectional Study to Measure Cough in Severe Asthma

NCT03999203 | Completed Results

• 1 other identifier: B17/03
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to characterise cough in severe asthma through an observational cross-sectional analysis of patients stratified by inflammatory biomarker profile using a number of subjective and objective cough measurement tools.

Conditions

Asthma; Cough

Outcome Measures

Primary Outcomes (2)

• Cough Frequency Measurement

  Objectively measure cough frequency (measured as hours per hour over a 24 hour monitoring period) in different phenotypes of severe asthma and a mild/moderate control group using a validated ambulatory cough monitor (Leicester Cough Monitor)

  Baseline

• Cough Reflex Sensitivity (Citric Acid Cough Challenge)

  To objectively measure cough reflex sensitivity in different phenotypes of severe asthma and a mild.moderate control group using citric acid cough challenge testing. Patients are asked to inhale increasing concentrations of citric acid solutions and the cough response to each is measured in the 15 seconds following. The final outcome endpoint is described as the concentrations needed to cause 2 coughs (C2)

  Baseline

Secondary Outcomes (6)

• Asthma Control Questionnaire

  Baseline

• Asthma Quality of Life Questionnaire

  Baseline

• Leceister Cough Questionnaire

  Baseline

• Cough Quality of Life Questionnaire

  Baseline

• Fractional Exhaled Nitric Oxide (FeNO)

  Baseline

Study Arms (4)

A - T2 High Severe Asthmatics

ACTIVE COMPARATOR

Severe asthmatic patients with eosinophil count ≥ 0.15x10\^9/mL andhigh FeNO levels ≥20 ppb. Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling

Drug: Citric acid; Device: Leicester Cough monitor; Other: fractional exhaled nitric oxide testing (FeNO); Other: Patient reported outcome measures

B - T2 Low Severe Asthmatics

ACTIVE COMPARATOR

Severe asthmatic patients with eosinophil count ≤ 0.15x10\^9/mL and low FeNO levels \<20 ppb. Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling

Drug: Citric acid; Device: Leicester Cough monitor; Other: fractional exhaled nitric oxide testing (FeNO); Other: Patient reported outcome measures

C - Mild/Moderate Asthmatics

ACTIVE COMPARATOR

mild/moderate severe asthmatics (defined as step 2/3 using the GINA classification of severity) recruited from general respiratory clinics in the Belfast HSC Trust Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling

Drug: Citric acid; Device: Leicester Cough monitor; Other: fractional exhaled nitric oxide testing (FeNO); Other: Patient reported outcome measures

D - T2 Intermediate

ACTIVE COMPARATOR

Severe asthmatic patients with eosinophil count ≥ 0.15x10\^9/mL OR high FeNO levels ≥20 ppb. Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling

Drug: Citric acid; Device: Leicester Cough monitor; Other: fractional exhaled nitric oxide testing (FeNO); Other: Patient reported outcome measures

Interventions

Citric acid DRUG

Citric Acid cough challenge to be administered to assess the cough reflex sensitivity in patients

A - T2 High Severe Asthmatics; B - T2 Low Severe Asthmatics; C - Mild/Moderate Asthmatics; D - T2 Intermediate

Leicester Cough monitor DEVICE

Ambulatory cough monitor to assess cough frequency over a 24 hour period

A - T2 High Severe Asthmatics; B - T2 Low Severe Asthmatics; C - Mild/Moderate Asthmatics; D - T2 Intermediate

fractional exhaled nitric oxide testing (FeNO) OTHER

Measurement of exhaled nitric oxide to give an indication of airway inflammation

A - T2 High Severe Asthmatics; B - T2 Low Severe Asthmatics; C - Mild/Moderate Asthmatics; D - T2 Intermediate

Patient reported outcome measures OTHER

A number a patient reported outcome measures will be administered including: Asthma control questionnaire (ACQ-5), mini Asthma Quality of Life Questionnaire (mini AQLQ), Leicester Cough Questionnaire (LCQ), Cough Quality of Life Questionnaire (CQLQ), Cough Hypersensitivity Questionnaire (CHQ) and visual analogue scales for severity og cough (VASc) and Urge to Cough (VASu)

A - T2 High Severe Asthmatics; B - T2 Low Severe Asthmatics; C - Mild/Moderate Asthmatics; D - T2 Intermediate

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability and willingness to comply with the study procedures
• Age ≥18 to ≤75 years at the time of informed consent
• Severe asthma (as defined by GINA step 4/5 classification of asthma severity) after a detailed systematic assessment
• History of asthma treatment with high doses of Inhaled Corticosteroids (≥1000 µg beclomethasone dipropionate daily, or equivalent) and an additional controller
• Three patient groups with severe asthma will be investigated in the study and will be defined as follows:
• T2-High Severe Asthmatics (Group A)
• Persistent blood eosinophil count ≥0.3x10\^9/mL and
• Persistent high FeNO levels ≥30 ppb and
• Adherence to inhaled and oral corticosteroid therapy
• T2-Low Severe Asthmatics (Group B)
• Persistent blood eosinophil count ≤0.2x10\^9/Ml and
• Persistent low FeNO levels (\<30ppb)
• T2 - Intermediate Severe Asthmatics (Group D)
• Persistent blood eosinophil count ≥ 0.3x10\^9/mL OR
• Persistent FeNO levels ≥ 30 ppb

You may not qualify if:

• Baseline FEV1 ≤50% of predicted or ≤ 1.0L
• Asthma exacerbation within 28 days before the time of informed consent or during screening
• Major episode of infection requiring any of the following:
• Admission to hospital for ≥24 hours within the 28 days before the time of informed consent
• Treatment with intravenous antibiotics within the 28 days before the time of informed consent or during Screening
• Treatment with oral antibiotics within the 14 days before the time of informed consent or during Screening
• For adults: Active tuberculosis (TB) requiring treatment within the 12 months before the time of informed consent (patients are also required to have no recurrence of symptoms in the 12 months following completion of TB treatment), or
• Diagnosis or history of malignancy, or current investigation for possible malignancy
• Other clinically significant medical disease that is uncontrolled despite treatment or that is likely, in the opinion of the investigator, to require a change in therapy or affect the ability to participate in the study
• History of alcohol, drug, or chemical abuse that would impair or risk the patient's full participation in the study, in the opinion of the investigator
• Current smoker or former smoker with a smoking history of \>15 pack-years A current smoker is defined as someone who has smoked one or more cigarettes per day (or marijuana or pipe or cigar) for ≥30 days within the 24 months before the time of informed consent and for whom cotinine testing is positive.
• A former smoker is defined as someone who has smoked one or more cigarettes per day (or marijuana or pipe or cigar) for ≥30 days in his or her lifetime (as long as the 30-day total did not include the 24 months before the time of informed consent) and for whom cotinine testing is negative.
• A pack-year is defined as the average number of packs per day times the number of years of smoking.
• Initiation of or change in allergen immunotherapy within three months before the time of informed consent
• Treatment with an investigational agent within 30 days of informed consent or 5 half-lives of the investigational agent, whichever is longer

Sponsors & Collaborators

• Queen's University, Belfast: lead
• King's College London: collaborator

Study Sites (1)

Queen's University Belfast

Belfast, BT7 1NN, United Kingdom

Location

MeSH Terms

Conditions

Asthma; Cough

Interventions

Citric Acid; Patient Reported Outcome Measures

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Citrates; Tricarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Health Care Surveys; Surveys and Questionnaires; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Services Research; Health Planning; Health Care Economics and Organizations; Patient Outcome Assessment; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Health Care Evaluation Mechanisms; Public Health; Environment and Public Health

Results Point of Contact

• Title: Professor Liam Heaney
• Organization: Queen's University Belfast

l.heaney@qub.ac.uk

02890976376

Study Officials

• Liam Heaney, MD

  Queen's University, Belfast

  PRINCIPAL INVESTIGATOR

• Lorcan McGarvey, MD

  Queen's University, Belfast

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 12, 2018
• First Posted: June 26, 2019
• Study Start: October 4, 2017
• Primary Completion: December 30, 2019
• Study Completion: December 30, 2019
• Last Updated: November 22, 2023
• Results First Posted: November 22, 2023

Record last verified: 2023-02

Locations

GB (1)