Azithromycin and Oesophageal Function in Respiratory Disease

Asthma Clinical Trial

Official title:

Exploring the Effect of Azithromycin on Oesophageal Motility and Respiratory Symptoms in Patients With Chronic Respiratory Disease: a Prospective Observational Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05469555
• Other study ID #: 315000
• Status: Recruiting
• Start date: June 29, 2023
• Est. completion date: November 1, 2024

Study information

• Verified date: April 2024
• Source: Hull University Teaching Hospitals NHS Trust
• Contact: Dominic L Sykes, MBBS, BSc
• Phone: 07769342595
• Email: dominic.sykes2[@]nhs.net
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Symptoms such as cough, wheeze, and breathlessness are among the most common reasons for general practitioner or emergency department visits in the UK. Such symptoms have a profound impact on patients' ability to live a fulfilled life, often rendering people unable to work and socialise. Azithromycin (a type of antibiotic) improves symptoms and reduces flare-ups of diseases such as asthma and chronic obstructive pulmonary disease (COPD). The reason why it works is unclear. Many people believe that it either decreases the number of bacteria in the lungs or reduces inflammation in the lungs and the upper airways. Neither theory is proven. Another possible mechanism that has been much less studied is that Azithromycin encourages the body to move food and fluid through the gut more quickly, thus preventing reflux and aspiration of small food particles and stomach acid. It has been shown that lung damage can occur when gut contents enter the airways, which may contribute chronic lung disease patients' symptoms In this study the investigators will test the effect of azithromycin on the gut in patients with chronic lung diseases. The investigators will measure the strength of a patients swallow by measuring the pressures in their gullet, using high-resolution oesophageal manometry (HROM), before and after treatment, in people being started on azithromycin as part of their routine care. The investigators will also measure the effect that azithromycin has on their symptoms and observe whether there is a relationship between the strength of their swallow and their symptoms. At the end of this study, the investigators hope to better understand the way in which azithromycin helps to improve the symptoms of patients with chronic lung diseases. The investigators also hope to open the door to investigate the effect of other drugs that improve gut function in patients with chronic lung diseases.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: November 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Males and females aged =18 years.
• Have a diagnosis of chronic respiratory disease (COPD, asthma, interstitial lung disease, chronic cough, cystic fibrosis, and/or bronchiectasis) confirmed by a respiratory consultant.
• Exhibit symptoms consistent with airway reflux, demonstrated by a score =14 on the Hull Airways Reflux Questionnaire
• Are being initiated on azithromycin as part of routine clinical care, as judged by their usual respiratory clinician. This will include all common treatment regimes, 250mg once daily, 250mg three times per week, and 500mg three time per week.
• Are willing and able to consent to all study procedures.

Exclusion Criteria:

• Previous treatment with long-term macrolides in the past 3 months.
• Unable to be investigated with HROM due to contraindications such as anatomical abnormalities or diseases of the oesophagus or unwilling/ unable to be investigated with HROM based on the clinical judgement of the investigators due to severity of lung disease.
• Have another cardiorespiratory cause for their symptoms (such as heart failure or lung cancer).
• Women of child bearing potential not using effective means of contraception.
• Are unable or unwilling to consent to or complete the study procedures.

Related Conditions & MeSH terms

• Asthma
• Copd
• Cough
• ILD
• Respiration Disorders
• Respiratory Tract Diseases

Intervention

Procedure:
• High Resolution Oesophageal Manometry
High Resolution Oesophageal manometry assesses how well the muscles of the oesophagus are working when you swallow. It also checks the relaxation of the valves at the top and bottom of the oesophagus.

Locations

Country	Name	City	State
United Kingdom	Castle Hill Hospital	Hull	Yorkshrie

Sponsors (1)

Lead Sponsor	Collaborator
Hull University Teaching Hospitals NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Eligibility to consent ratio	The ratio of participants deemed eligible to participate in the study to the number of those who provide consent to take part	1 year
Primary	Recruitment rate	The number of participants successfully recruited per month	1 year
Primary	Participant retention to follow-up	The proportion of those participants who consent to take part that compete all study measures to follow-up	1 year
Primary	Acceptability of assessment	Quantify the proportion of participants who judge the study investigations, principally HROM, to be acceptable.	1 year
Secondary	Distal Contractile Integrity	To evaluate the effect of azithromycin on the contraction vigour and swallow coordination. This will be evaluated by investigating patients with HROM before and 1 month after initiation of azithromycin as part of routine clinical care. Measured in mmHg/sec/cm.	1 month
Secondary	Lower Oesophageal Sphincter Pressure	To evaluate the effect of azithromycin on the pressure of the lower oesophageal sphincter as measured by HROM. This will be evaluated by investigating patients with HROM before and 1 month after initiation of azithromycin as part of routine clinical care. Measured in mmHg.	1 month
Secondary	Distal Latency	To evaluate the effect of azithromycin on the timeframe of the wave from the beginning of the swallow to an inflection of the peristaltic axis, as measured by HROM. This will be evaluated by investigating patients with HROM before and 1 month after initiation of azithromycin as part of routine clinical care. Measured in seconds.	1 month
Secondary	Integrated Relaxation Pressure.	To evaluate the effect of azithromycin on the oeosphageal pressure topography metric that is used for assessing the adequacy of oesophageogastric junction relaxation, as measured by HROM. This will be evaluated by investigating patients with HROM before and 1 month after initiation of azithromycin as part of routine clinical care. Measured in seconds.	1 month
Secondary	Chicago Classification	A composite classification based on all HROM measurements. We will be using the current version 4.0.	1 month
Secondary	Hull Airway Reflux questionnaire	A validated tool for assessing symptoms of reflux. A likert scale questionnaire. Scored out of 70 with higher score representing worse symptoms.	1 month
Secondary	Breathlessness, cough, and sputum scale	A validated tool for assessing symptom burden. A 5-point likert scale that is scored out of 12. A higher score representing worse symptoms.	1 month
Secondary	MRC dyspnoea scale	A validated tool for measuring breathlessness. It is scored out out of 5 with a higher score representing worse symptoms.	1 month
Secondary	Visual analogue scale - cough severity	A visual scale of 100mm in length. Participants will mark on the scale from 0-100 how bad their cough is currently with 100mm representing worst cough imaginable.	1 month
Secondary	COPD Assessment test (COPD patients only)	An 8 item questionnaire which quantifies the symptom burden participants with COPD and how it impacts their life. Scored out of 40, with a higher score signifying worse control.	1 month
Secondary	Asthma control questionnaire (asthma patients only)	An 7 item questionnaire which quantifies the symptom burden participants with asthma and how it impacts their life. Scored 5-25 - a score of 5 is very poorly controlled asthma and a score of 25 is very well controlled asthma.	1 month
Secondary	Numerical rating scale - breathlessness severity	A horizontally arranged scale numbered 0-10 with 0 representing no breathlessness and 10 representing the worst breathlessness imaginable	1 month
Secondary	Leicester Cough Questionnaire	A 19-item questionnaire with a 7-point Likert scale used to assess the impact of cough on physical, social, and psychological welfare of the patient. It is scored out of 133 with a higher score representing better health.	1 month
Secondary	St. George's Respiratory Questionnaire	A 50-item questionnaire which assess impact of overall health, daily life, and well-being in patients with obstructive airways disease. Scores range from 0-100, with higher scores indicating more limitations.	1 month
Secondary	King's Brief Interstitial Lung Disease Questionnaire (ILD Patients only)	A 15-item 7-point Likert scale questionnaire aimed to measure the impact of ILD on quality of life and health status. It is scored out of 100, with 100 representing the best health status.	1 month
Secondary	Relationship between oesophageal motility and symptoms	The change in oesophageal functioning and presence of respiratory symptoms will be examined in each participant. The relationship between these two parameters will then be examined using statistical analysis	1 month