Clinical trial NCT05570981: A Comprehensive Evaluation of the Impact of ATP on Laryngeal Symptoms, Hypersensitivity and Function
Official title: A Comprehensive Evaluation of the Impact of ATP on Laryngeal Symptoms, Hypersensitivity and Function - an Observational Controlled Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Refractory Cough
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
Collaborators: name: Royal Brompton & Harefield NHS Foundation Trust
First posted: 2022-10-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult patients (≥ 18 years) with chronic refractory cough and age-/gender matched healthy controls.

Brief summary: OBJECTIVES

* To deliver a comprehensive model of laryngeal assessment, evaluating both the sensory and motor components of upper airway control and to relate this to symptom disturbance.
* Determine if laryngeal control is altered by coughing and the impact of repeated coughing on overall laryngeal control and relaxation to its baseline state.
* Evaluate if cell damage and tissue inflammation (including exposure to ATP) modulates laryngeal hypersensitivity and function, by using a comprehensive array of test modalities.

AIM To utilise state-of-the-art comprehensive assessment tools to evaluate laryngeal hypersensitivity and function in a cohort of individuals with chronic refractory cough and control subjects. The test modalities utilise direct stimulation of the laryngeal adductor reflex, measurement of laryngeal EMG and assessment of functional laryngeal response to an inhalational challenge with laryngoscopic techniques.

HYPOTHESIS Physiological markers of laryngeal hypersensitivity and dysfunction are highly prevalent in patients with chronic refractory cough and manifestations are driven by ATP stimulation.

OUTCOME MEASURES Measurements of laryngeal symptomatology will be measured over a run-in period and during challenge testing. Laryngeal relaxation will be studied using our novel tracking software capability, combining endoscopic imaging and physiological measurements of diaphragm activation.


Eligibility criteria: Inclusion criteria (controls)

* Age ≥ 18 years
* Healthy - with no history of any medical conditions
* No history of asthma / allergies
* Normal spirometric indices
* Non smoker

Inclusion criteria (patients)

* Age ≥ 18 years
* Chronic cough as per ATS definition (\>8 weeks duration)
* High symptom burden (i.e. Cough VAS \>= 40 mm at the screening visit)
* Chest radiograph or CT within 3 years of the screening visit with no abnormalities considered to contribute to chronic cough
* For patients with asthma: a confirmed diagnosis of asthma on the basis of asthma symptoms and reversible airflow obstruction (BDR 200mls + 12% change post bronchodilator and/or positive bronchoprovocation test).

Exclusion criteria

* Current smoker or a smoking history of \>10 pack years
* Asthma that is not well-controlled, as per international asthma guidelines as specified by Global Initiative for Asthma (GINA)
* Recent exacerbation of cough or asthma within 4 weeks of inclusion
* Pregnancy or childbearing potential and no contraceptive treatment
* Respiratory tract infection within 4 weeks of inclusion
* Currently taking any of the following medications:

  * ACE inhibitors and within 3 months of inclusion
  * Antitussives (opioids, pregabalin, gabapentin, amitriptyline, nortriptyline or over-the-counter medications) within 2 weeks of inclusion
  * Medical treatments for GORD, eosinophilic bronchitis or other cough related conditions, initiated or changed (i.e. not in a stable regimen) for 4 weeks prior to inclusion.
* Medical history of COPD or chronic bronchitis
* Medical conditions/history or other circumstances which, in the judgement of the investigator, could increase the risk of adverse events or bias the study results

Primary outcomes:
measure: Maximal decrease in glottic anterior angle (degrees) during challenge testing
timeFrame: Baseline measurement is taken immediately before beginning the challenge test. Minimal value is taken from continuously measured glottic anterior angle, from immediately after baseline measurement and until immediately after challenge testing
measure: Maximal increase in glottic anterior angle (degrees) after challenge testing
timeFrame: During challenge testing and from immediately after challenge testing until 5 minutes after challenge testing
measure: Maximal laryngeal relaxation time (seconds)
timeFrame: At baseline, during challenge testing and from immediately after challenge testing until 5 minutes after challenge testing
measure: Change in laryngeal relaxation time (seconds) during challenge testing
timeFrame: At baseline and immediately after challenge testing
measure: Change in laryngeal relaxation time (seconds) in recovery
timeFrame: Immediately after challenge testing and at 5 minutes after challenge testing
Secondary outcomes:
measure: Cough VAS (0-100 mm)
timeFrame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
measure: Cough count and frequency
timeFrame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
Other outcomes:
measure: Breathing frequency (1/minute)
timeFrame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
measure: Breathing frequency variability (entropy, unitless)
timeFrame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
measure: Tidal volume (Litres)
timeFrame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
measure: Tidal volume variability (entropy, unitless)
timeFrame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
measure: Diaphragm activation (Root Mean Square of EMG mcV in a rolling 50ms window centered at the measureing point)
timeFrame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
measure: Oesophageal pressure (cmH2O)
timeFrame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
measure: Gastric pressure (cmH2O)
timeFrame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
measure: Trans-diaphragmatic pressure (cmH2O)
timeFrame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
measure: Single cough episode duration (seconds)
timeFrame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
measure: Single cough episode intensity VAS (0-100 mm)
timeFrame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing
Locations:
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
Study officials:
References: