EVH + Mannitol for Cough Variant Asthma

Overseen By M. Diane Lougheed, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Dr. Diane Lougheed

Disqualifiers: Recent exacerbation, Spirometry inability, Methacholine contraindications, Smoking, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how two treatments, Eucapneic Voluntary Hyperventilation (EVH) and Mannitol, affect individuals with cough variant asthma (CVA) and those with a chronic cough triggered by methacholine. Researchers will compare their responses to those of healthy individuals without these conditions. The goal is to determine if these treatments cause breathing problems and coughing in the affected groups but not in healthy individuals. Those who have experienced a persistent cough for more than eight weeks, either from CVA or methacholine-triggered cough, may be suitable candidates for this study. As a Phase 4 trial, this research focuses on understanding how these already FDA-approved treatments can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that previous treatment with inhaled or systemic corticosteroids is not an exclusion criterion. Your medication use will be recorded and examined during the study.

What is the safety track record for Eucapneic Voluntary Hyperventilation and Mannitol?

Research has shown that Eucapneic Voluntary Hyperventilation (EVH) and hypertonic saline tests are generally safe for studies. These tests might cause a cough in some people but are usually well-tolerated. Past studies have used these methods to help diagnose asthma and other breathing issues without major safety concerns.

Methacholine challenge testing, another part of this study, is a common way to check for asthma. It involves inhaling a substance that can temporarily narrow the airways, aiding in the diagnosis of breathing problems. Previous patients demonstrated that this method is safe, though it may cause mild coughing or shortness of breath for a short time.

Both tests have been used in clinical settings and are considered safe for research. They mimic asthma symptoms, allowing doctors to better understand and treat breathing conditions. For those considering joining a trial with these tests, the risk of serious side effects is low based on available data. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Eucapneic Voluntary Hyperventilation (EVH) and Hypertonic Saline (HS) challenge tests for Cough Variant Asthma because these approaches offer a fresh perspective on diagnosing and understanding asthma-related coughs. Unlike standard treatments that typically involve inhaled corticosteroids or bronchodilators, these tests focus on assessing airway responsiveness, which can provide deeper insights into how coughs are triggered and managed. By using hypertonic saline and hyperventilation as triggers, these methods might help identify underlying mechanisms specific to Cough Variant Asthma, potentially leading to more personalized and effective treatment strategies in the future.

What evidence suggests that this trial's treatments could be effective for cough variant asthma?

Research has shown that certain tests can effectively detect airway sensitivity in people with asthma, including cough variant asthma (CVA). In this trial, participants with CVA will undergo tests such as the Eucapneic Voluntary Hyperventilation (EVH) and Hypertonic Saline (HS) Challenge Tests. These tests have demonstrated that 84% of people with asthma had a strong reaction to a test using salty water, while healthy individuals had only a minor reaction. Another group in the trial will undergo Methacholine (MCh) Challenge Testing, which helps identify CVA by causing the airways to narrow, confirming asthma-like symptoms in those who mainly experience a cough. These methods are valuable for assessing and diagnosing different types of asthma by showing how the airways respond to specific challenges. ^{3 4 6 7 8}

Who Is on the Research Team?

M. Diane Lougheed, MD, MSc

Principal Investigator

Department of Medicine, Queen's University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with cough variant asthma or chronic cough due to methacholine-induced cough but normal airway sensitivity. It's also open to healthy individuals without a history of asthma or chronic cough. People can't join if they've had a recent exacerbation, can't do proper lung function tests, have conditions that make the methacholine test unsafe, or have smoked heavily.

Inclusion Criteria

I have had a chronic cough for over 8 weeks and it improved with asthma treatment.

I have had a cough for over 8 weeks and passed a specific breathing test.

Exclusion Criteria

I cannot perform a lung function test properly.

I've had a health issue in the last month that required changing my medication or a hospital visit.

You have medical reasons that make it unsafe for you to do the methacholine challenge test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Challenge Testing

Participants undergo eucapneic voluntary hyperventilation (EVH) and Mannitol challenges to assess sensory-mechanical responses

1-2 weeks

2-3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after challenge tests

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Eucapneic Voluntary Hyperventilation (EVH) and Hypertonic Saline (HS) Challenge Tests
• Methacholine (MCh) Challenge Testing

Trial Overview The study aims to understand how people with certain types of coughs and healthy controls respond to two different stimuli: breathing exercises (EVH) and Mannitol inhalation. Researchers want to see if these cause symptoms like shortness of breath and whether there are differences in lung mechanics between groups.

How Is the Trial Designed?

Group I: Methacholine-induced cough Experimental Treatment 3 Interventions

Individuals with chronic cough and negative methacholine challenge

Group II: Cough Variant Asthma Experimental Treatment 3 Interventions

Individuals diagnosed with Cough variant asthma

Group III: Control Experimental Treatment 3 Interventions

Individuals with no history of asthma or chronic cough

Who Is Running the Clinical Trial?

Dr. Diane Lougheed

Lead Sponsor

Trials

2

Recruited

60+

Dr. Diane Lougheed

Lead Sponsor

Trials

2

Recruited

60+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/2178963/

Inhalational challenge using hypertonic saline in asthmatic ... In normal subjects the FEV1 was reduced by 6 +/- 2% (mean +/- SD) after inhalation of 33 ml of aerosol. Eighty four percent of the asthmatic subjects exhibited ...

2. jacionline.org jacionline.org/article/S0091-6749(08)01137-8/fulltext

Exercise and other indirect challenges to demonstrate ... This article reviews and describes the symptom-based diagnosis, the exercise challenge, and other indirect challenges such as eucapnic voluntary hyperpnea.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4963444/

Eucapnic Voluntary Hyperpnea: Gold Standard for ... This article provides a state-of-the-art review of EVH, including an overview of the test methodology and its interpretation.

4. publications.ersnet.org publications.ersnet.org/content/erj/21/6/1050

Indirect airway challenges | European Respiratory Society A reduction in FEV1 of 10% of the pre-exercise value is widely accepted as outside the response observed in healthy individuals without asthma. Eucapnic ...

5. researchgate.net researchgate.net/publication/7905272_Methods_for_Indirect_Challenge_Tests_Including_Exercise_Eucapnic_Voluntary_Hyperpnea_and_Hypertonic_Aerosols

(PDF) Methods for "Indirect" Challenge Tests Including ... Eucapnic voluntary hyperpnea was developed later, as a surrogate test for exercise. Hypertonic aerosols were introduced to mimic the dehydrating ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3205007/

Cough response to isocapnic hyperpnoea of dry air and ... We investigated whether there is an association between cough response induced by IHDA and hypertonic saline (HS) challenges.

7. withpower.com withpower.com/trial/phase-4-cough-8-2021-49a83

EVH + Mannitol for Cough Variant Asthma The objectives of this study are to determine the sensory-mechanical responses to Eucapneic Voluntary Hyperventilation (EVH) and Mannitol in individuals ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8569027/

Utility of Cough Provocation Tests in Chronic Cough and ... ... eucapnic voluntary hyperventilation, and hypertonic saline. The ... Investigating the safety of capsaicin cough challenge in severe asthma.