Mechanisms of Change in Behavioral Cough Suppression Therapy for Refractory Chronic Cough
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 135
- 试验地点
- 5
- 主要终点
- Cough threshold sensory testing (CTT)
研究概览
简要总结
This study is testing new ways to help people who have chronic cough that has not improved with typical treatments. One approach is called behavioral cough suppression (BCS) therapy, which teaches people techniques to stop themselves from coughing. Another approach uses a natural substance thought to help reduce the body's sensitivity to cough triggers.
In this study, we will test two treatments and include one no-treatment control group. The control group will undergo baseline testing, cough monitoring, and an fMRI brain scan and will be offered BCS at end of study participation.
The two treatments include:
- BCS therapy with active inhaled treatment (BCS+active),
- BCS therapy with inactive inhaled treatment (BCS+inactive),
The investigators will enroll 135 adults with refractory chronic cough (RCC). 100 participants who qualify and are willing and able to complete 14 study visits in the clinic and two online study visits will be randomly assigned to one of the two treatments. The no-treatment control group (n=35) will be recruited from adults with RCC who are willing to complete baseline testing and fMRI but are not able or willing to attend 14 study clinic visits. These participants will not be randomized.
The investigators want to find out how these treatments affect:
- How sensitive someone is to things that make them cough,
- How well they can hold back a cough when they try,
- How their brain responds to things that cause an urge-to-cough,
- And how much their coughing affects their quality of life.
The investigators believe both treatments will reduce sensitivity to cough stimulants, reduce cough severity, and improve quality of life, but BCS+active inhaled treatment will work better than BCS+inactive inhaled treatment.
详细描述
Refractory chronic cough (RCC) is a persistent and costly condition that is difficult to treat, often persisting despite appropriate treatment of underlying causes. While behavioral cough suppression (BCS) therapy has shown effectiveness in reducing cough frequency and improving quality of life in controlled studies, it remains underutilized, and the mechanisms by which it works are not well understood.
This multi-site randomized controlled trial will investigate the effects and mechanisms of BCS therapy with and without the addition of an inhaled substance designed to enhance the effect of BCS treatment. The active inhaled substance used in the study has demonstrated desensitization effects on sensory pathways in conditions such as chronic rhinitis and pain syndromes, suggesting potential utility in modulating cough-related neural pathways. Inhalation of this substance has been shown to be safe across multiple studies.
The investigators will recruit 135 participants diagnosed with RCC. 100 participants will be randomized into one of two treatment arms -- BCS combined with an active inhaled substance, and BCS combined with an inactive inhalant. A non-randomized no-treatment control group (n=35) will be included to provide a control comparison to fMRI.
Participants in the treatment arms will undergo 12 treatment sessions over several weeks. The study will evaluate both behavioral and neural markers of treatment response. Primary outcome measures will include:
- Cough sensory threshold (C5): the lowest concentration of citric acid causing five or more coughs,
- Cough suppression ability (CS Thresh Diff): the ability to suppress cough when instructed, quantified by the difference between the dose of capsaicin causing five or more coughs when trying to suppress cough (CS5) and C5,
- Urge-to-cough (UTC) sensory-motor threshold difference (UTC S-M Thresh Diff): a measure of how perception of the need to cough relates to actual coughing behavior,
- Blood oxygen level dependent (BOLD) neural responses using whole-brain functional MRI (fMRI) during UTC stimulation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible to participate, participants must meet the following criteria:
- •18 - 99 years of age
- •Diagnosis of refractory or unexplained chronic cough
- •Normal chest imaging (x-ray or CT scan) within past 2 years, without change in cough symptoms
- •If you a potential participant has asthma, the following criteria must be met:
- •Asthma diagnosed by a pulmonary provider
- •Documentation from a pulmonary provider that asthma is well-controlled
- •Agree to carry prescribed rescue inhaler to each study visit
- •Can tolerate, and agree to, avoid rescue inhaler use for 4 hours prior to each study visit. If rescue inhaler use is unavoidable within 4 hours of a study visit, agree to inform researchers in advance so that the session can be rescheduled.
- •Normal pulmonary function testing with spirometry (FEV1/FVC of at least 70% if diagnosed with asthma) within 2 years (6 months for those with a diagnosis of asthma), without change in symptoms since (NOTE: spirometry is included as part of cough threshold testing and can serve as this criteria if the participant has not had spirometry within the designated time.)
- •Laryngoscopy or stroboscopy within 2 years without evidence of structural pathology and no change in vocal quality since exam
- •Proficient reader/speaker of English
- •Willing to take a pregnancy test before enrollment (if applicable)
- •Willing to use contraception during the study (if applicable)
- •Access to reliable internet, working email address (for surveys) and a smart phone (for use with CoughMonitor Watch)
- •Demonstrates understanding in study procedures and risks in order to consent
- •Available, and willing, to comply to all study procedures and clinic visits.
排除标准
- •Any of the following will be grounds for exclusion from the study:
- •Currently a smoker of any substance or has a positive history of smoking any substance within the last 6 months
- •Currently suffering from any signs of an upper respiratory infection (other than cough)
- •Hemoptysis (coughing up blood) within the last 6 months
- •Pulmonary diagnosis other than asthma
- •Asthma criteria - participant is deemed ineligible if screened for one or more of the following:
- •Use of rescue inhaler in response to active asthma symptoms ≥ 2 times per week
- •Respiratory related emergency department visit within the past 4 weeks
- •Respiratory related ICU admission within the past 12 months
- •Asthma exacerbation requiring systemic corticosteroid use within the past 4 weeks
- •Pregnant or trying to become pregnant
- •Any complaints or clinical symptoms of dysphagia
- •Live with someone with chronic cough or work with someone with chronic cough who is in close proximity (e.g., within 25 feet) on a daily or nearly daily basis
- •Known allergy to peppers
- •Currently receiving or has received BCS therapy for management of refractory chronic cough
- •Excluded concomitant medications:
- •Inhaled pulmonary medications (inhaled corticosteroids, short-acting beta agonists, long-acting beta-agonist, short-acting muscarinic antagonists), unless prescribed for asthma by pulmonary provider: 30 days prior to Visit 1 through completion of study participation
- •ACE inhibitor (benazepril, captopril, enalapril, fosiniopril, lisinopril, perindopril, quinapril, ramipril, trandolapril): 30 days prior to Visit 1 through completion of study participation.
- •Narcotic antitussive (hydrocodone, oxycodone, morphine, codeine, tramadol): 7 days prior to Visit 1 through completion of study participation
- •Non-narcotic antitussive (benzonatate/Tessalon, dextromethorphan/Delsym, carbetapentane/Solotuss): 7 days prior to Visit 1 through completion of study
- •P2X3 receptor antagonist (gefapixant/Lyfnua): 14 days prior to Visit 1 through completion of study
- •Any off-label prescription medication prescribed for cough (pregabalin/Lyrica, gabapentin/Neurontin, amitriptyline/Elavil): 14 days prior to Visit 1 through completion of study *if a neuromodulator is prescribed for something other than cough, participant must be on a stable dose for a minimum of 7 days
- •The following additional exclusion criteria will apply to participants who will undergo fMRI:
- •Presence of metal implants, devices or fragments (e.g., shrapnel) in the body
- •Claustrophobia
研究组 & 干预措施
Behavioral treatment plus inactive drug
Participants receive behavioral cough suppression therapy (BCST) combined with an inactive inhaled substance.
干预措施: BCS+inactive (Behavioral)
Behavioral treatment plus inhaled drug
Participants receive behavioral cough suppression (BCS) therapy combined with inhaled drug designed to enhance BCS therapy
干预措施: BCS+active (Combination Product)
fMRI Control
Participants will undergo assessments without treatment
结局指标
主要结局
Cough threshold sensory testing (CTT)
时间窗: From enrollment to 4 weeks following enrollment
Measure of cough sensitivity using progressive doses of inhaled vaporized citric acid. The dose causing 5 or more coughs (C5) is the endpoint.
Cough suppression threshold difference (CS Thresh Diff)
时间窗: From enrollment to 4 weeks following enrollment
Measure of cough suppression ability. The participant first completes cough suppression threshold testing which involves inhalation of progressive doses of citric acid while actively trying to suppress cough. The dose causing 5 or more coughs when trying to not cough (CS5) is the endpoint. CS Thresh Diff is the difference between CS5 and C5.
Urge-to-Cough Sensory Motor Threshold Difference (UTC S-M Thresh Diff)
时间窗: From enrollment to 4 weeks following enrollment
A measure of the relationship between sensation of UTC and motor action of coughing. The measure is determined by calculating the difference between first UTC felt during cough threshold testing (Cu) and UTC at the dose of citric acid that causes 2 or more coughs (C2) (i.e., UTC at C2 - UTC at Cu).
Blood oxygen level dependent neural responses (BOLD)
时间窗: 4 weeks following enrollment BCS+CAP and BCS+Sham participants; enrollment to 1 week post-enrollment for the fMRI control group
Whole-brain fMRI performed during inhalation of capsaicin to trigger urge-to-cough. (NOTE: this measure is only required for those enrolling at Univ. of Colorado)
Cough threshold sensory testing (CTT)
时间窗: From enrollment to 14 weeks following enrollment
Measure of cough sensitivity using progressive doses of inhaled vaporized citric acid. The dose causing 5 or more coughs (C5) is the endpoint.
Cough suppression threshold testing (CSTT)
时间窗: From enrollment to 14 weeks following enrollment
Measure of cough suppression ability using progressive doses of inhaled vaporized citric acid. The dose causing 5 or more coughs when trying to not cough (CS5) is the endpoint.
Urge-to-Cough Sensory Motor Threshold Difference (UTC S-M Thresh Diff)
时间窗: From enrollment to 14 weeks following enrollment
A measure of the relationship between sensation of UTC and motor action of coughing. The measure is determined by calculating the difference between first UTC felt during cough threshold testing (Cu) and UTC at the dose of citric acid that causes 2 or more coughs (C2) (i.e., UTC at C2 - UTC at Cu).
Blood oxygen level dependent neural responses (BOLD)
时间窗: From enrollment to 14 weeks following enrollment
Whole-brain fMRI performed during inhalation of capsaicin to trigger urge-to-cough. (NOTE: this measure is only required for those enrolling at Univ. of Colorado)
次要结局
- Leicester Cough Questionnaire (LCQ)(From enrollment to 19 weeks following enrollment)
- Cough frequency(From enrollment to 11 weeks following enrollment)
- Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ)(From enrollment to 19 weeks following enrollment)
- Voice Handicap Index - 10 (VHI-10)(From enrollment to 19 weeks following enrollment)
- Multidimensional Assessment of Interoceptive Awareness (MAIA-2)(From enrollment to 8 weeks following enrollment)
- PROMIS - Global Health(From enrollment to 11 weeks following enrollment)
- PROMIS - Sleep(From enrollment to 8 weeks following enrollment)
- Patient Global Impression of Severity (PGI-S)(From enrollment to 19 weeks following enrollment)
- Patient Global Impression of Change (PGI-C)(From enrollment to 19 weeks following enrollment)
- Study Specific Questions (3; 3-SSQ)(From enrollment to 19 weeks following enrollment)
- Leicester Cough Questionnaire (LCQ)(From enrollment to 23 weeks following enrollment)
- Cough frequency(From enrollment to 14 weeks following enrollment)
研究者
Laurie Slovarp
Professor
University of Montana