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?

This trial explores how well albuterol, a common asthma medication, can assist women with Lymphangioleiomyomatosis (LAM), a rare lung disease that obstructs airflow. The study compares two delivery methods for albuterol: a nebulizer and an inhaler, to determine which one better improves lung function. Women experiencing breathing difficulties due to LAM might be suitable candidates for this trial. Participants will stay at the National Institutes of Health for a few days to test each method and measure lung function. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works and assess its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

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.

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

Research shows that albuterol, whether used with a nebulizer or an inhaler, is generally safe and well-tolerated. Studies have found that about 30% of patients with lymphangioleiomyomatosis (LAM) experience improved breathing with albuterol, indicating that the treatment can open airways without causing major problems.

Albuterol is a familiar medication often used for asthma and other breathing issues. It has been used for a long time, and most people tolerate it well. Some side effects might include a fast heartbeat or slight shaking, but these are usually mild and temporary.

In this early-stage trial (Phase 1/2), the main goal is to confirm safety and determine the best dose. This phase involves checking for any side effects and ensuring the treatment is safe. Since albuterol is already approved for other conditions, its safety is well understood, which should reassure potential trial participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Albuterol for lymphangioleiomyomatosis (LAM) because it offers a new approach to managing this rare lung condition. Unlike the current standard treatments for LAM, which often include sirolimus or everolimus to slow disease progression, Albuterol is a bronchodilator that can directly improve lung function by relaxing airway muscles. This could provide immediate relief from breathing difficulties, offering a complementary option to the existing therapies that primarily focus on long-term disease management. The use of both inhaler and nebulizer forms allows flexibility in delivery, catering to patient preference and specific clinical needs.

What evidence suggests that albuterol might be an effective treatment for LAM?

Research has shown that albuterol, whether used with a nebulizer or an inhaler, can improve lung function in people with Lymphangioleiomyomatosis (LAM). About one-third of LAM patients with breathing difficulties respond to medications like albuterol that open the airways. One study found that approximately 30% of LAM patients experienced a 12% improvement in lung function when using albuterol. This trial will compare the effectiveness of albuterol delivered via nebulizer, one treatment arm, with albuterol delivered via inhaler, another treatment arm, to determine which method might help LAM patients breathe better. ^{1 2 3 4 6}

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

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]

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 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]

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01799538

NCT01799538 | Nebulized or Inhaled Albuterol for ... 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.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11355058/

Inhalational Drug Devices: Revisiting the Linchpin of Asthma ... This review will discuss the anatomy and physiology behind drug delivery via inhalers, the types of inhalers currently available for use, nebulizers, and ...

3. med.upenn.edu med.upenn.edu/rare-lung-diseases/information-for-doctors.html

Information for Doctors | Laboratory of Rare Lung Diseases The subjects will be provided with a short-acting β2-agonist for symptom relief during the study (albuterol sulfate, Ventolin® HFA). Subjects who remain ...

4. cc.nih.gov cc.nih.gov/recruit/protocols/13_lam

Albuterol in Patients With Lymphangioleiomyomatosis One possible treatment to improve breathing in patients with LAM is inhaled albuterol. Albuterol can be given using a hand held inhaler or with a nebulizer.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0169409X20300363

Post-inhalation cough with therapeutic aerosols This review provides an assessment of post-inhalation cough with therapeutic aerosols. Factors that increase cough may be mitigated through design of the drug, ...

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, ...