Bronchodilator Therapy for Cystic Fibrosis

Overseen By Satvir S Dhillon, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Disqualifiers: Chronic airway infection, Organ transplantation, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a bronchodilator, a medicine that opens airways, can reduce shortness of breath and improve exercise ability in adults with cystic fibrosis (CF). CF is a genetic disease that causes thick mucus to block the airways, making breathing difficult. Participants will use either the bronchodilator salbutamol or a placebo to determine which is more effective. Individuals with a confirmed CF diagnosis, who experience breathlessness, and do not smoke might be suitable for this trial. As an unphased trial, it offers participants the chance to contribute to important research that could enhance future CF treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that salbutamol, a medication that opens the airways, is generally safe for people with cystic fibrosis (CF). Studies have found that it can improve lung function when taken before exercise and was well-tolerated by participants.

However, like any medication, it can cause side effects. Common side effects of salbutamol include shaking and nausea, which most people find mild.

While salbutamol can aid breathing, studies also indicate it does not significantly enhance exercise performance in CF patients. Considering both the potential benefits and side effects is important when deciding to join a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for cystic fibrosis primarily focus on managing symptoms and reducing lung infections. However, salbutamol is unique because it acts as a bronchodilator that directly relaxes the muscles in the airways, making it easier to breathe. Unlike some standard therapies that may take longer to show benefits, salbutamol can provide rapid relief from breathing difficulties. Researchers are excited about this treatment because its fast-acting nature could significantly improve the quality of life for people with cystic fibrosis by providing quick and effective relief from airway constriction.

What evidence suggests that this trial's treatments could be effective for cystic fibrosis?

Research shows that salbutamol, a type of inhaler, can help individuals with cystic fibrosis (CF) breathe better. Studies have found that it can increase the amount of air exhaled in one breath, improving breathing in both children and adults with CF. Some individuals notice significant improvement, especially when using salbutamol before exercising. However, while it may ease breathing, it might not make exercising feel easier. Overall, salbutamol is considered safe and can provide short-term relief for those with CF. Participants in this trial will receive either a salbutamol metered-dose inhaler or a placebo metered-dose inhaler to evaluate salbutamol's effectiveness in this context. ^{1 2 6 7 8}

Who Is on the Research Team?

Jordan A Guenette, PhD

Principal Investigator

University of British Columbia - Centre for Heart Lung Innovation

Are You a Good Fit for This Trial?

This trial is for adults with cystic fibrosis who experience difficulty breathing and limited exercise capacity. Eligible participants must have a specific range of lung function, be between the ages of 19 and older, have a body mass index from 16 to 30, and cannot currently smoke or have a heavy past smoking history. People with certain infections or other diseases affecting breathing, those needing supplemental oxygen, or with a history of organ transplantation can't join.

Inclusion Criteria

I am 19 years old or older.

My health condition is currently stable.

I am a non-smoker or have smoked less than 20 pack-years.

Exclusion Criteria

I have a condition besides CF that affects my breathing or ability to exercise.

I have a long-term lung infection with specific bacteria.

I need extra oxygen or my oxygen levels drop below 80% when I exercise.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Assessment

Medical history screening, chronic activity-related dyspnea, quality of life, and physical activity questionnaires, anthropometric measurements, pulmonary function assessment, and a symptom-limited incremental cycle exercise test

1 week

1 visit (in-person)

Treatment

Participants undergo constant-load cycle exercise tests with inhalation of either 400 μg salbutamol or placebo in a crossover design

5 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Salbutamol

Trial Overview The study is testing whether Salbutamol—a bronchodilator medication that helps open up the airways in the lungs—can effectively reduce shortness of breath and improve exercise performance in CF patients compared to a placebo (a substance with no therapeutic effect).

How Is the Trial Designed?

Group I: Salbutamol meter-dose inhaler Active Control 1 Intervention

Inhalation of 400 μg salbutamol

Group II: Placebo meter-dose inhaler Placebo Group 1 Intervention

Inhalation of 400 μg placebo

Salbutamol is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Ventolin for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchoconstriction
• High blood potassium levels

Approved in United States as Albuterol/Ventolin for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchoconstriction
• High blood potassium levels

Approved in Canada as Ventolin for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchoconstriction
• High blood potassium levels

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Published Research Related to This Trial

The study found significant differences in the fine particle doses of albuterol sulfate among the three inhalers: Ventolin delivers 21 μg, Proventil delivers 40 μg, and ProAir delivers 64 μg, indicating that Proventil and ProAir provide 2 to 3 times more medication likely to reach the lungs compared to Ventolin.

Using a valved holding chamber (VHC) effectively reduces the delivery of larger particles from all three inhalers without affecting the fine particle dose, suggesting that VHCs can enhance the therapeutic efficacy of these inhalers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a holding chamber on albuterol metered-dose inhaler product differences. Johnson, JL., Guthrie, D., Hyde, J., et al.[2017]

Endotracheal administration of albuterol was successfully used in a 67-year-old woman with severe asthma, leading to significant improvement in her clinical status and arterial blood gases.

This method of delivering albuterol directly to the bronchial tree is effective for intubated asthmatic patients, allowing for rapid recovery and extubation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of asthma-related respiratory arrest with endotracheal albuterol (salbutamol). Verbeek, PR., Gareau, AB., Rubes, CJ.[2019]

Lipid microparticles (LMs) were successfully developed to provide a sustained release of salbutamol sulphate, a common bronchodilator for asthma, using the spray congealing technique.

The optimal formulation achieved a drug loading of 4.72% and a particle size suitable for effective delivery, indicating potential for improved asthma treatment through prolonged medication release.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of spray congealing and melt emulsification methods for the incorporation of the water-soluble salbutamol sulphate in lipid microparticles. Scalia, S., Traini, D., Young, PM., et al.[2013]

In a study of nine healthy subjects, intravenous salbutamol (SAL) at a dose of 20 microg/min significantly increased minute ventilation (VE) by 37.8%, along with increases in oxygen consumption (VO2) and CO2 production (VCO2), indicating that SAL raises metabolic demands.

The rise in ventilation was linked to increased serum lactate levels and a decrease in base excess, suggesting that SAL can induce lactic acidosis, which may pose risks for asthmatic patients with limited ventilatory capacity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms by which systemic salbutamol increases ventilation. Tobin, AE., Pellizzer, AM., Santamaria, JD.[2022]

In a double-blind controlled trial involving nine patients with severe chronic airway obstruction, all participants preferred nebulized salbutamol over placebo, indicating its potential efficacy in improving symptoms.

Patients showed significant improvements in morning and evening peak flow measurements and reported lower symptom scores for breathlessness, wheezing, and sputum production during the active treatment period, suggesting that nebulized salbutamol may be beneficial for those not responding to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Domiciliary nebulised salbutamol solution in severe chronic airway obstruction. Wilson, RS., Connellan, SJ.[2019]

In a study involving 24 asthmatic patients, both HFA 134a salbutamol sulfate and CFC 11/12 salbutamol showed equivalent improvements in lung function (FEV1 and FVC) after inhalation, indicating similar efficacy.

The safety profiles of both medications were comparable, with no significant differences in heart rate, blood pressure, or adverse events, suggesting that HFA 134a salbutamol sulfate is a safe alternative to CFC 11/12 salbutamol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cumulative dose-response study of non-CFC propellant HFA 134a salbutamol sulfate metered-dose inhaler in patients with asthma. Kleerup, EC., Tashkin, DP., Cline, AC., et al.[2019]

A study involving 10 healthy volunteers found no significant differences in lung bioavailability between generic (Salamol, Salbulin) and innovator (Ventolin) formulations of inhaled salbutamol, indicating similar effectiveness in delivering the medication to the lungs.

All formulations produced comparable plasma salbutamol levels and urinary excretion rates, suggesting that both generic and innovator inhalers can be used interchangeably without loss of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung bioavailability of generic and innovator salbutamol metered dose inhalers. Clark, DJ., Gordon-Smith, J., McPhate, G., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15978535/

Inhaled beta-agonists improve lung function but not ... Conclusions: In adults with CF, salbutamol improves post-exercise FEV1 and is safe when administered immediately before exercise but does not improve exercise ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7387861/

Short‐acting inhaled bronchodilators for cystic fibrosis - PMC To evaluate short‐acting inhaled bronchodilators in children and adults with CF in terms of clinical outcomes and safety.

3. pulmonologyadvisor.com pulmonologyadvisor.com/news/the-effects-of-salbutamol-inhalation-on-children-with-cystic-fibrosis/

The Effects of Salbutamol Inhalation on Patients With ... In pediatric patients with cystic fibrosis (CF), bronchodilator inhalation with salbutamol is likely to have a positive short-term effect of on forced ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0012369216311400

A Controlled Trial of Long-term Bronchodilator Therapy in ... Responders showed greater maximum improvement by day 28 while taking albuterol (45 ± 42 L/min) than they did while taking placebo (22 ± 17 L/min; p = 0.03, ...

5. respiratory-therapy.com respiratory-therapy.com/disorders-diseases/chronic-pulmonary-disorders/cystic-fibrosis/salbutamol-inhalation-pediatric-cystic-fibrosis/

Positive Response to Salbutamol Inhalation in Cystic Fibrosis ... Salbutamol inhalation had a positive short-term effect on forced expiratory volume in pediatric cystic fibrosis patients.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00634517

4-Week Study of Efficacy, Safety and PK of Albuterol-HFA ... This 4-week clinical study evaluates the efficacy and safety of Albuterol Sulfate HFA Inhalation Aerosol in comparison with the Active Control, ...

7. cff.org cff.org/managing-cf/bronchodilators

Bronchodilators You may experience adverse side effects when you take any medication, including bronchodilators. Common side effects of albuterol include: Tremor. Nausea ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0012369215490488

Effect of Albuterol on Maximal Exercise Capacity in Cystic ... The current study demonstrates that inhaled albuterol does not improve indexes of maximal exercise performance in CF subjects with moderate severity airways ...