Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Mannitol

NCT03105843 | Recruiting Phase 4

• 1 other identifier: 2023-17
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The objectives of this study are to determine the sensory-mechanical responses to Eucapneic Voluntary Hyperventilation (EVH) and Mannitol in individuals with cough variant asthma (CVA) and methacholine-induced cough with normal airway sensitivity (COUGH) and compare these responses to a control group of healthy individuals without asthma or chronic cough. We hypothesize:

1. 1.EVH and Mannitol cause dyspnea, cough, small airway obstruction with resultant dynamic hyperinflation, gas trapping and autoPEEP in individuals with CVA and COUGH, but not healthy controls.
2. 2.The sensory-mechanical responses to both hyperosmolar challenges (EVH and Mannitol) are comparable within groups (CVA, COUGH and healthy controls).

Conditions

Asthma; Cough; Cough Variant Asthma

Keywords

Asthma; Cough; Eucapneic Voluntary Hyperventilation; Hypertonic Saline

Outcome Measures

Primary Outcomes (1)

• Mid expiratory flows

  The bronchodilating effect of a DI will be examined using responses to the challenge testing (Visit 2/3) in these subgroups by comparing the mid-expiratory flow difference between the partial (PEF) and full maximal flow-volume (MEF) loops at 40% above Residual Volume (RV) from the forced vital capacity (FVC) (PEF40 and MEF40 respectively) at provocative dose of 4.5% saline causing a 20% decline in FEV1 (PD20 (HS)) and provocative minute ventilation causing a 20% decline in FEV1 (PC20 (EVH)) with that recorded at baseline.

  Time frame of the methacholine challenge varies between individuals. At provocative dose/ventilation causing a 20% decline in FEV1 (PD20 and PC20 respectively). On average, these occur about 15-25 minutes into the challenge test

Secondary Outcomes (5)

• Respiratory System Reactance (X5)

  After dose administration; will occur 2-5 minutes after dose

• Peripheral Resistance (R5-R20)

  After dose administration; will occur 2-5 minutes after dose

• Central Airway Resistance

  After dose administration; will occur 2-5 minutes after dose

• Forced Vital Capacity (FVC)

  After dose administration; will occur 2-5 minutes after dose

• FEV1/FVC

  After dose administration; will occur 2-5 minutes after dose

Study Arms (3)

Cough Variant Asthma

EXPERIMENTAL

Individuals diagnosed with Cough variant asthma

Drug: Methacholine (MCh) Challenge Testing; Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH); Drug: Mannitol Inhalation Kit

Methacholine-induced cough

EXPERIMENTAL

Individuals with chronic cough and negative methacholine challenge

Drug: Methacholine (MCh) Challenge Testing; Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH); Drug: Mannitol Inhalation Kit

Control

EXPERIMENTAL

Individuals with no history of asthma or chronic cough

Drug: Methacholine (MCh) Challenge Testing; Diagnostic Test: Eucapneic Voluntary Hyperventilation (EVH); Drug: Mannitol Inhalation Kit

Interventions

Methacholine (MCh) Challenge Testing DRUG

Visit 1: Informed consent, Baseline screening and pulmonary function tests and Low-dose methacholine challenge testing using partial and full flow-volume loops.

Also known as: MCh[inhalation of sequential doubling doses of MCh(0.0625-16 mg/mL)], Provocholine

Control; Cough Variant Asthma; Methacholine-induced cough

Eucapneic Voluntary Hyperventilation (EVH) DIAGNOSTIC_TEST

Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.

Control; Cough Variant Asthma; Methacholine-induced cough

Mannitol Inhalation Kit DRUG

Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.

Also known as: Mannitol Challenge Test

Control; Cough Variant Asthma; Methacholine-induced cough

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals aged 18-65 years of age with CVA and individuals with methacholine-induced cough but normal airway sensitivity. The following definitions will be used:
• CVA: chronic cough (≥8 weeks) is the sole or predominant symptom and positive methacholine challenge (PC20 ≤ 16 mg/mL) and history of cough responding to specific asthma treatment (such as inhaled steroid or 1 week trial of bronchodilator);
• Methacholine-induced cough but normal airway sensitivity: chronic cough (≥8 weeks) is the sole or predominant symptom and negative methacholine challenges (PC20 \> 16 mg/mL).
• Individuals aged 18-65 years of age with no history of asthma or chronic cough.

You may not qualify if:

• an exacerbation necessitating a change in medication, emergency department visit or hospitalizations within the previous 4 weeks
• inability to perform acceptable spirometry
• medical contraindications to methacholine challenge testing

Sponsors & Collaborators

• Dr. Diane Lougheed: lead

Study Sites (1)

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

RECRUITING

MeSH Terms

Conditions

Asthma; Cough; Cough-Variant Asthma

Interventions

Methacholine Chloride

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methacholine Compounds; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds

Study Officials

• M. Diane Lougheed, MD, MSc

  Department of Medicine, Queen's University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

M. Diane Lougheed, MD, MSc

CONTACT

613-548-2348; diane.lougheed@kingstonhsc.ca

Taylar Wall, RRT

CONTACT

613-549-6666; taylar.wall@kingstonhsc.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 4, 2017
• First Posted: April 10, 2017
• Study Start: March 1, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)