Effect of Over-the-counter Non-steroidal Anti-inflammatory Treatments on Cough Reflex Sensitivity in Subjects with Upper Respiratory Tract Infection
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 1
- 主要终点
- Change in objective measures of cough sensitivity
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
盲法说明
The study will involve one-way blinding. Participants will be made aware prior to consenting that they will receive either flurbiprofen or a control intervention during the initial briefing and screening communications. However, they will not be told if the intervention they receive will contain flurbiprofen, a low dose of flurbiprofen, or no flurbiprofen. Blinding of the researchers to the identity of the treatment is difficult to achieve in practice given the physical characteristics of the interventions. Regardless of this, the researchers don't have any subjective role in quantifying the endpoint measures (patient-reported outcomes and cough sensitivity), minimising the risk of influencing the findings. For these reasons, the pragmatic approach of single blinding of the experiment is appropriate, acknowledging that this experiment is not designed to be a true clinical trial.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •An onset of any 2 URTI symptoms in past 3-5 days, such as a sore throat, fever, coughing, coughing up phlegm, sneezing, and runny nose;
- •A current cough or urge-to-cough rated at least 5 in severity and/or ranking cough as subject's most bothersome symptom on Cold Symptoms Questionnaire (CSQ);
- •A feeling of sickness interfering with their daily life, rated as at least mildly;
- •A cough consistent with acute cough - i.e., cough onset with URTI and not ongoing, chronic cough;
- •Written informed consent and a willingness and ability to comply with the study protocol.
排除标准
- •A pre-existing chronic lung disease (asthma, COPD, chronic bronchitis etc), to exclude these as causes for cough;
- •The use of inhaled or systemic steroids / broncho-active medication, ACE inhibitors, oral or inhaled antihistamines, opiates, gabapentin, tricyclic antidepressants (current or within the past 3 months), as these will alter airway inflammatory profiles and/ or cough sensitivity;
- •A current cigarette or marijuana smoker/vaper, recreational drug user, or have given up smoking/vaping within the last 12 months, or a former smoker with greater than 20 pack-years, alter airway inflammatory profiles and/ or cough sensitivity;
- •Pre-existing chronic cough (cough persisting for more than 8 weeks): unexplained chronic cough (UCC) or refractory chronic cough (RCC) associated with or without a pre-existing condition (GERD, rhinitis, etc), as we are studying acute cough;
- •Prior experience of an allergic or bad reaction to capsaicin or chilli (which is rare);
- •Prior experience an allergic or bad reaction to a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen;
- •Ongoing or history of stomach ulcer, impaired kidney or liver function, or heart failure;
- •Pregnancy, lactation or actively trying to become pregnant;
- •Currently taking other products with flurbiprofen, aspirin or other anti-inflammatory medicines;
- •Evidence of COVID-19 positivity, either during the COVID Rapid Antigen Test administered on the day of assessment or have informed us that they have become positive in the 24-48 hours after the testing session (i.e., participants who were likely positive during assessment but under the detection threshold);
- •Participants who cannot provide informed voluntary consent.
研究组 & 干预措施
Flurbiprofen Oral Lozenge
30 participants will be asked to suck one (1) flurbiprofen 8.75 mg honey and lemon lozenge (tradename: Strepfen) until dissolved.
干预措施: Flurbiprofen Oral Lozenge (Drug)
Placebo lozenge
30 participants will be asked to suck one (1) non-medicated Difflam Soothing Drops + Immune Support Honey & Lemon flavour lozenge until dissolved.
干预措施: Difflam (Drug)
Flurbiprofen 8.75 MG
30 participants will be asked to perform three (3) oral actuations (2.91 mg per actuation) of flurbiprofen 8.75mg spray.
干预措施: Flurbiprofen 8.75 MG (Drug)
Low dose flurbiprofen spray
30 participants will be asked to perform one (1) oral actuation of flurbiprofen 8.75 mg spray, equivalent to a 2.91mg dosage. This will serve a a low dose control as there is no placebo spray available.
干预措施: Flurbiprofen 8.75 MG (Drug)
结局指标
主要结局
Change in objective measures of cough sensitivity
时间窗: Cough challenge testing will be performed at baseline and 3 hours after intervention.
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.
次要结局
- Change in Cold Symptoms Questionnaire (CSQ) score(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(Nasal fluid samples will be taken at baseline and at 3 hours post-intervention.)
- Change in levels of inflammatory markers in saliva samples(Saliva samples will be taken at baseline and at 3 hours post-intervention.)
- Change in levels of inflammatory markers in pharyngeal lavage samples(Pharyngeal lavage samples will be taken at baseline and at 3 hours post-intervention.)
- Patients' Global Impression of Change score(Participants self-report using the Patients' Global Impression of Change score at 3 hours post-intervention.)
研究者
Stuart Mazzone
Professor in Neuroscience
University of Melbourne