Albuterol for LAM

Recruiting at 1 trial location

Overseen By Tatyana A Worthy, R.N.

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Must not be taking: MAO inhibitors, Tricyclics, Beta-blockers, others

Disqualifiers: Hypersensitivity to albuterol, Seizures, Cognitive impairment, others

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

Compensation: Varies

Number of Visits: 4

Duration: 3 days

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Background: - Lymphangioleiomyomatosis (LAM) is a rare type of lung disease that occurs almost exclusively in women. In LAM, muscle tissue grows in the lungs and starts to block the flow of air. It is a progressive disease, and in severe cases may require a lung transplant. One possible treatment to improve breathing in people with LAM is inhaled albuterol. Albuterol can be given in a metered dose inhaler (MDI) or with a nebulizer. Researchers want to compare these methods to see which method best improves lung function in women with LAM. Objectives: - To see whether a nebulizer or MDI can better improve lung function in women with LAM. Eligibility: - Women at least 18 years of age who have impaired lung function because of LAM. Design: * Participants will be screened with a physical exam and medical history. No lab tests will be needed for this study. * Participants will have a 3-day overnight stay at the National Institutes of Health. Those who are using long-acting inhalers will have to stop taking these drugs 1 week before the study. * Participants will receive either the nebulizer or two or four puffs of the inhaler. Four puffs of albuterol is a higher dose than is normally prescribed, and is being tested on this study. * Participants will have each treatment around the same time of day on each of the 3 days. Before and after taking the albuterol, participants will have lung function tests.

Do I need to stop my current medications for the trial?

If you are using long-acting inhalers, you must stop taking them 1 week before the study. Also, if you are on monoamine oxidase inhibitors, tricyclic antidepressants, beta-adrenergic receptor antagonists, or long-acting anticholinergic bronchodilators, you need to discontinue them at least 7 days before enrollment.

What safety data exists for Albuterol treatments?

The safety of Albuterol treatments, including Proventil HFA and Ventolin, has been evaluated in several studies. One study found that Proventil HFA and Ventolin have similar safety profiles during regular use over 12 weeks. Another study compared HFA 134a salbutamol sulfate with CFC salbutamol and found no significant differences in safety, including pulse rate, blood pressure, and ECG intervals. Patients switched from CFC to HFA albuterol showed comparable safety and efficacy, with similar adverse event profiles, except for increased asthma symptoms and rhinitis in the CFC group. Overall, HFA albuterol formulations are considered safe and effective alternatives to CFC formulations. ^{1 2 3 4 5}

Is Albuterol a promising drug for LAM?

Albuterol, known by names like Ventolin HFA and ProAir HFA, is a promising drug because it effectively helps open up the airways, making it easier to breathe. Studies show it works well over time and has a similar safety profile to other options. ^{1 2 6 7 8}

What data supports the idea that Albuterol for LAM is an effective drug?

The available research shows that Albuterol, known by various brand names like Proventil HFA and Ventolin, is effective in providing bronchodilation, which means it helps open up the airways in the lungs. This is demonstrated in studies where Albuterol was compared to other treatments for asthma, showing similar effectiveness in improving breathing over 12 weeks. Although the studies focus on asthma, they suggest that Albuterol can effectively improve lung function, which may be beneficial for conditions like LAM. However, there is no specific data provided for LAM in the available research. ^{1 2 6 7 8}

Who Is on the Research Team?

Joel Moss, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

This trial is for women over 18 with Lymphangioleiomyomatosis (LAM), a rare lung disease. They must have specific lung function impairments and may have a diagnosis based on tissue biopsy, organ involvement, or high VGEF-D levels. Excluded are those post-transplant, allergic to albuterol, with certain health conditions like seizures or major systemic diseases, pregnant/breastfeeding women, and those unable to stop certain medications before the study.

Inclusion Criteria

Your lungs have trouble moving air in and out, and your breathing test results are not within the normal range.

I have been diagnosed with LAM through a biopsy, symptoms in lungs and other organs, high VEGF-D levels, or TSC with lung cysts.

Exclusion Criteria

You are unable to stop taking bronchodilators for 24 hours.

I do not have severe thyroid issues, uncontrolled GERD, or major diseases like cancer or severe diabetes.

I have difficulty with memory or thinking clearly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive either nebulized albuterol or inhaled albuterol for 3 consecutive days, with lung function tests conducted before and after each treatment

3 days

3 visits (in-person, overnight stay)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Albuterol Inhaler
• Albuterol Nebulizer

Trial Overview The trial aims to compare two methods of delivering albuterol—a medication that helps open airways—to see which improves lung function in LAM patients better: an inhaler (MDI) or a nebulizer. Participants will stay overnight for three days at NIH and receive either treatment while their lung function is tested before and after administration.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 2 Interventions

Nebullizer

Group II: 2 Active Control 2 Interventions

Inhaler

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

Approved in United States as Albuterol for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchospasm

Approved in European Union as Salbutamol for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchospasm

Approved in Canada as Albuterol for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchospasm

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study involving 38 patients with mild-to-moderate persistent asthma, all three formulations of formoterol (including Modulite HFA) significantly improved lung function and bronchoprotection compared to placebo.

Modulite HFA formoterol was found to be effective and well tolerated, showing similar efficacy to other formoterol delivery methods, indicating it is a viable option for asthma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bronchoprotective and bronchodilator effects of an HFA pMDI vs. a CFC pMDI and a DPI containing formoterol in asthma patients. Langley, SJ., Houghton, CM., Singh, SD.[2015]

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]

In a study involving 30 patients with stable mild to moderate asthma, both formoterol and albuterol provided similar and rapid bronchodilation, with significant improvements in lung function measured by FEV1 at 3 minutes after inhalation.

Both treatments were well tolerated, indicating that formoterol (9 microg) and albuterol (200 microg) are effective options for quick relief in asthma management, with no significant differences in efficacy between the two.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the bronchodilating effects of formoterol and albuterol delivered by hydrofluoroalkane pressurized metered-dose inhaler. Ankerst, J., Lötvall, J., Cassidy, S., et al.[2019]

Proventil HFA demonstrated bronchodilator effectiveness comparable to Ventolin over a 12-week period, significantly outperforming the HFA-134a placebo in improving lung function as measured by FEV1.

Both Proventil HFA and Ventolin showed a decrease in bronchodilator response after 4 weeks of regular use, indicating a potential reduction in efficacy over time with continued treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proventil HFA provides bronchodilation comparable to ventolin over 12 weeks of regular use in asthmatics. Bleecker, ER., Tinkelman, DG., Ramsdell, J., et al.[2021]

Proventil HFA (albuterol) demonstrated a safety profile similar to Ventolin over 12 weeks of treatment in asthmatic patients, with no significant adverse events reported compared to a placebo.

Both Proventil HFA and Ventolin effectively maintained asthma control without deterioration, as indicated by stable asthma symptom scores and minimal changes in vital signs and laboratory tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proventil HFA and ventolin have similar safety profiles during regular use. Tinkelman, DG., Bleecker, ER., Ramsdell, J., et al.[2019]

A study comparing CFC albuterol and HFA albuterol in asthma patients over 12 weeks found no significant differences in bronchodilator efficacy, indicating that HFA albuterol is just as effective as CFC albuterol.

Patients switched to HFA albuterol reported fewer asthma symptoms and rhinitis compared to those who continued with CFC albuterol, suggesting a potential improvement in overall patient comfort and safety with the new propellant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching patients with asthma from chlorofluorocarbon (CFC) albuterol to hydrofluoroalkane-134a (HFA) albuterol. Bronsky, E., Ekholm, BP., Klinger, NM., et al.[2016]

The inhaler fluticasone propionate/formoterol (FP/FORM) has a longer plume duration and slower velocity compared to fluticasone propionate/salmeterol (FP/SAL), which may enhance drug delivery to the lungs.

FP/FORM produces a warmer and less forceful plume, potentially improving lung deposition of the medication, which is important for effective treatment in respiratory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plume Characteristics of Two HFA-Driven Inhaled Corticosteroid/Long-Acting Beta2-Agonist Combination Pressurized Metered-Dose Inhalers. Johal, B., Murphy, S., Tuohy, J., et al.[2022]

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]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Bronchoprotective and bronchodilator effects of an HFA pMDI vs. a CFC pMDI and a DPI containing formoterol in asthma patients. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

The effect of a holding chamber on albuterol metered-dose inhaler product differences. [2017]

3. United States pubmed.ncbi.nlm.nih.gov

Comparison of the bronchodilating effects of formoterol and albuterol delivered by hydrofluoroalkane pressurized metered-dose inhaler. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Proventil HFA provides bronchodilation comparable to ventolin over 12 weeks of regular use in asthmatics. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Proventil HFA and ventolin have similar safety profiles during regular use. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Switching patients with asthma from chlorofluorocarbon (CFC) albuterol to hydrofluoroalkane-134a (HFA) albuterol. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Plume Characteristics of Two HFA-Driven Inhaled Corticosteroid/Long-Acting Beta2-Agonist Combination Pressurized Metered-Dose Inhalers. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Cumulative dose-response study of non-CFC propellant HFA 134a salbutamol sulfate metered-dose inhaler in patients with asthma. [2019]