A Comprehensive Evaluation of the Impact of ATP on Laryngeal Symptoms, Hypersensitivity and Function

NCT05570981 | Unknown DMC

• 1 other identifier: H-21076805
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Refractory Cough

Outcome Measures

Primary Outcomes (5)

• Maximal decrease in glottic anterior angle (degrees) during challenge testing

  The maximal decrease in glottic anterior angle during challenge testing

  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

• Maximal increase in glottic anterior angle (degrees) after challenge testing

  The difference between the minimal glottic anterior angle observed during challenge testing and the maximal glottic anterior angle observed from immediately after challenge testing and until 5 minutes after challenge testing

  During challenge testing and from immediately after challenge testing until 5 minutes after challenge testing

• Maximal laryngeal relaxation time (seconds)

  Maximum time for glottic angle to normalise (i.e. achieve a value equal to or above the value prior to sensory stimulus)

  At baseline, during challenge testing and from immediately after challenge testing until 5 minutes after challenge testing

• Change in laryngeal relaxation time (seconds) during challenge testing

  Change in time for glottic angle to normalise (i.e. achieve a value equal to or above the value prior to sensory stimulus)

  At baseline and immediately after challenge testing

• Change in laryngeal relaxation time (seconds) in recovery

  Change in time for glottic angle to normalise (i.e. achieve a value equal to or above the value prior to sensory stimulus)

  Immediately after challenge testing and at 5 minutes after challenge testing

Secondary Outcomes (2)

• Cough VAS (0-100 mm)

  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

• Cough count and frequency

  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 (10)

• Breathing frequency (1/minute)

  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

• Breathing frequency variability (entropy, unitless)

  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

• Tidal volume (Litres)

  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

Study Arms (2)

Chronic Refractory Cough (CRC)

Individuals with a diagnosis of chronic refractory cough

Diagnostic Test: Laryngeal sensitivity testing

Healthy controls

Healthy control subjects matched to the CRC group by age and gender

Diagnostic Test: Laryngeal sensitivity testing

Interventions

Laryngeal sensitivity testing DIAGNOSTIC_TEST

Direct stimulation of the laryngeal adductor reflex, measurement of laryngeal EMG and our capability to assess functional laryngeal response to an inhalational challenge with laryngoscopic techniques.

Chronic Refractory Cough (CRC); Healthy controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult patients (≥ 18 years) with chronic refractory cough and age-/gender matched healthy controls.

You may qualify if:

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

You may not qualify if:

• 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)
• Pregnancy or childbearing potential and no contraceptive treatment
• Currently taking any of the following medications:
• 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

Sponsors & Collaborators

• Bispebjerg Hospital: lead
• Royal Brompton & Harefield NHS Foundation Trust: collaborator

Study Sites (1)

Bispebjerg Hospital

Copenhagen, 2400, Denmark

RECRUITING

Central Study Contacts

Emil Walsted, MD PhD

CONTACT

(+45)30338750; emilwalsted@dadlnet.dk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: October 7, 2022
• Study Start: November 28, 2022
• Primary Completion: July 31, 2023
• Study Completion: December 31, 2023
• Last Updated: December 1, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)