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Effect of Over-the-counter NSAIDS on Cough Reflex Sensitivity in Patients With Upper Respiratory Tract Infections
The goal of this mechanism of disease study is to investigate the effect of flurbiprofen, a non-steroidal anti-inflammatory drug (NSAID), on the cough hypersensitivity associated with upper respiratory tract infections (URTI). The main questions it aims to answer are: * Q1: Does a single treatment with an approved therapeutic dose of flurbiprofen, an NSAID that prevents the production of prostaglandins, acutely reduce objective measures of cough hypersensitivity in participants with URTI? * Q2: Is the effect of flurbiprofen on cough hypersensitivity in URTI related to participant subjective ratings of acute cough severity? * Q3: Is the effect of flurbiprofen on cough hypersensitivity in URTI related to the levels of prostaglandins or other inflammatory markers measurable in upper airway secretions? Participants will be asked to undergo cough challenge testing, complete quality of life questionnaires, and have their nasal fluid, saliva and pharyngeal secretions sampled before and after a single treatment with flurbiprofen in the form of a lozenge or spray. Participants in the comparator arms of the study will instead receive a placebo lozenge or low dose flurbiprofen spray.
Study details:
People with an Upper Respiratory Tract Infection (URTI), for example the common cold, often exhibit heightened sensitivity to stimuli that cause coughing. This heightened sensitivity is thought to contribute to the short-term excessive coughing that accompanies the infection. What causes the heightened sensitivity is not known but may involve inflammation in the throat.
HYPOTHESIS: The investigators hypothesise that in URTI prostaglandins may lead to cough hypersensitivity by either a direct or indirect action on cough nerve fibre endings in the larynx, lowering their activation threshold to cough stimuli. OVERALL AIM: This study aims to investigate this hypothesis by assessing whether a single treatment with flurbiprofen, an existing over the counter anti-inflammatory drug (NSAID) medication contained in some 'cold and flu remedies' and used to relieve sore throat in URTI, reduces heightened cough sensitivity through a reduction in throat inflammation. The investigators will recruit 120 otherwise healthy male and female adults experiencing an URTI with acute cough for laboratory assessments lasting 5-6 hours.
OBJECTIVES: The primary objective is to assess whether flurbiprofen, in commercially available lozenge or spray formulations, reduces an individual's sensitivity to a cough evoking stimulus by assessing participant responsiveness to inhaled capsaicin. Capsaicin is the naturally occurring 'hot' component of chilli peppers and commonly used to investigate the cough reflex in humans. The secondary objectives are to assess the effect of flurbiprofen on:.
A. subjective measures of cough and urge-to-cough using questionnaires that assess Patient Reported Outcomes (PROs); and, B. the levels of chemical mediators of inflammation present in nasal secretions and saliva, to investigate flurbiprofen's potential mechanism of action.
METHOD: The investigators will test the hypothesis by measuring in participants their cough thresholds, subjective experiences with cough and urge-to-cough, and levels of airway prostaglandins and other inflammatory mediators, before and after a single treatment of flurbiprofen, which blocks the production of prostaglandins.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : Yes
Gender eligible for study: All
Things to know
Study dates
Study start: 2023-07-01
Primary completion: 2024-07-01
Study completion finish: 2024-07-01
Study type
BASIC_SCIENCE
Phase
EARLY_PHASE1
Trial ID
NCT05955885
Intervention or treatment
DRUG: Flurbiprofen Oral Lozenge
DRUG: Difflam
DRUG: Flurbiprofen 8.75 MG
Conditions
- • Cough
- • Upper Respiratory Tract Infections
Find a site
Closest Location:
University of Melbourne
Research sites nearby
Select from list below to view details:
University of Melbourne
Carlton, Victoria, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Flurbiprofen Oral Lozenge
| DRUG: Flurbiprofen Oral Lozenge
|
PLACEBO_COMPARATOR: Placebo lozenge
| DRUG: Difflam
|
EXPERIMENTAL: Flurbiprofen 8.75 MG
| DRUG: Flurbiprofen 8.75 MG
|
OTHER: Low dose flurbiprofen spray
| DRUG: Flurbiprofen 8.75 MG
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Change in objective measures of cough sensitivity | Participants' cough sensitivity thresholds will be measured by inhaled cough challenge testing. This involves participants inhaling single breaths of increasing concentrations of a tussigenic stimulus (capsaicin; (active component of hot chili peppers) as well as saline control to determine threshold doses that elicit an urge to cough, two coughs (C2) and five coughs (C5). The principal endpoint is measured as the change in capsaicin concentration needed to elicit cough responses and the unit of measure is micromolar. | Cough challenge testing will be performed at baseline and 3 hours after intervention. |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Change in Cold Symptoms Questionnaire (CSQ) score | Participants will be asked to self-report on their cold symptom severity using the Cold Symptoms Questionnaire. Each item requires rating on a 10-point Likert scale from 1 to 10. A higher score indicates a worse outcome. The principal endpoint is measured as the change in Cold Symptoms Questionnaire score and the unit of measure is points. | Participant self-reports using the Cold Symptoms Questionnaire at baseline and every 30 min after invention until 3 hours has elapsed. |
Change in levels of inflammatory markers in nasal fluid samples | Samples of nasal fluid will be taken from participants and levels of inflammatory markers such as prostaglandins will be measured using liquid chromatography-mass spectroscopy. The principle endpoint is measured as change in levels and the unit of measure is points. A higher score indicates a better outcome. | Nasal fluid samples will be taken at baseline and at 3 hours post-intervention. |
Change in levels of inflammatory markers in saliva samples | Samples of saliva will be taken from participants and levels of inflammatory markers such as prostaglandins will be measured using liquid chromatography-mass spectroscopy. The principle endpoint is measured as change in levels and the unit of measure is points. A higher score indicates a better outcome. | Saliva samples will be taken at baseline and at 3 hours post-intervention. |
Change in levels of inflammatory markers in pharyngeal lavage samples | Samples of pharyngeal fluid and tissue will be collected from a lavage and levels of inflammatory markers such as prostaglandins will be measured using liquid chromatography-mass spectroscopy. The principle endpoint is measured as change in levels and the unit of measure is points. A higher score indicates a better outcome. | Pharyngeal lavage samples will be taken at baseline and at 3 hours post-intervention. |
Patients' Global Impression of Change score | Participants will self-report on their overall impression of whether the intervention they received resulted in any perceivable changes in their coughing/urge-to-cough. This questionnaire contains mixed items, including items that require rating of degree of change of symptoms on a 10 point Likert scale. The principal endpoint is the score for each item and the unit of measure is points.A higher score indicates a worse outocme. | Participants self-report using the Patients' Global Impression of Change score at 3 hours post-intervention. |
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