Nebulized or Inhaled Albuterol for Lymphangioleiomyomatosis

NCT ID: NCT01799538

Last Updated: 2025-12-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-10
• Study Completion Date: 2027-11-01

Brief Summary

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.

Detailed Description

We have reported that approximately one third of patients with lymphangioleiomyomatosis (LAM) who have airflow obstruction respond to bronchodilators such as albuterol, a Beta2-adenergic receptor agonist, with an increase in forced expiratory flow in one second (FEV1) of 12% and 200 ml above baseline values. Others however, have questioned these findings, reporting instead, a low rate of response of only six percent. Contrasting with our study, in this study albuterol was administered with a metered dose inhaler whereas in ours it was given by nebulizer. We propose to measure changes in lung function after administration of albuterol, respectively by metered inhaler and nebulizer, for 3 consecutive days in 100 LAM subjects. Our hypothesis is that albuterol administered by nebulization will produce a greater increase in FEV1 than two puffs of inhaled albuterol. If this hypothesis is confirmed, then we may recommend that patients with LAM and airflow obstruction use as a method of drug administration a nebulizer, rather than a metered dose inhaler.

Conditions

Lymphangioleiomyomatosis

Keywords

Albuterol; Bronchodilator; Nebulizer; Metered Dose Inhaler

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Nebullizer

Group Type: EXPERIMENTAL

albuterol nebulizer

Intervention Type: DRUG

Albuterol administered by nebulization will produce a greater increase in FEV1

PFT

Intervention Type: PROCEDURE

Breathing Test

2

Inhaler

Group Type: ACTIVE_COMPARATOR

albuterol inhaler

Intervention Type: DRUG

2 puffs of Metered Dose inhaler for Bronchodilation

PFT

Intervention Type: PROCEDURE

Breathing Test

Interventions

albuterol inhaler

2 puffs of Metered Dose inhaler for Bronchodilation

Intervention Type: DRUG

albuterol nebulizer

Albuterol administered by nebulization will produce a greater increase in FEV1

Intervention Type: DRUG

PFT

Breathing Test

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Diagnosis of LAM either by tissue biopsy, evidence of lung and other organ involvement (renal angiomyolipomas, chylous effusions, lymphangioleiomyomas), high serum levels of vascular endothelial growth factor D (VGEF-D)(1) or a diagnosis of TSC associated with cystic lung lesions.
• Age 18 years or over
• Evidence of airflow obstruction: FEV1/VC ratio < fifth percentile of predicted normal and an FEV(1) <80% predicted of the normal values.

Exclusion Criteria

Subjects will be excluded from the study if they meet one or more of the following criteria:

• History of hypersensitivity to albuterol or any of its components.
• Moderate or large pleural effusions (chest x-ray and or CT scan procedure completed under Protocol 95-H-0186)
• History of seizures other than during infancy
• Inability to withhold bronchodilators for 24 hours
• Cognitive Impairment
• Age less than 18 years
• Male sex
• Status-post lung or kidney transplantation
• Pregnant or breast feeding (women of childbearing potential will undergo a blood or urine pregnancy test under Protocol 95-H-0186).
• Treatment with monoaminoxidase inhibitors, tricyclic antidepressants or Beta-adrenergic receptor antagonists or long acting anticholinergic bronchodilators who are unable to be discontinued for at least seven days before enrollment.
• Patients with URI, uncontrolled hyperthyroidism or severe gastro-esophageal reflux. Major systemic diseases (i.e., malignancy; myocardial infarction or unstable angina; type 1 diabetes, severe hypertension; liver cirrhosis).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joel Moss, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Heart, Lung, and Blood Institute (NHLBI)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Tatyana A Worthy, R.N.

Role: CONTACT

Phone: (301) 827-1376

Email: worthyt@mail.nih.gov

Joel Moss, M.D.

Role: CONTACT

Phone: (301) 496-1597

Email: mossj@nhlbi.nih.gov

References

McCormack FX. Lymphangioleiomyomatosis: a clinical update. Chest. 2008 Feb;133(2):507-16. doi: 10.1378/chest.07-0898.

Reference Type: BACKGROUND

PMID: 18252917 (View on PubMed)

Ryu JH, Moss J, Beck GJ, Lee JC, Brown KK, Chapman JT, Finlay GA, Olson EJ, Ruoss SJ, Maurer JR, Raffin TA, Peavy HH, McCarthy K, Taveira-Dasilva A, McCormack FX, Avila NA, Decastro RM, Jacobs SS, Stylianou M, Fanburg BL; NHLBI LAM Registry Group. The NHLBI lymphangioleiomyomatosis registry: characteristics of 230 patients at enrollment. Am J Respir Crit Care Med. 2006 Jan 1;173(1):105-11. doi: 10.1164/rccm.200409-1298OC. Epub 2005 Oct 6.

Reference Type: BACKGROUND

PMID: 16210669 (View on PubMed)

Costello LC, Hartman TE, Ryu JH. High frequency of pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex. Mayo Clin Proc. 2000 Jun;75(6):591-4. doi: 10.4065/75.6.591.

Reference Type: BACKGROUND

PMID: 10852420 (View on PubMed)

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2013-H-0051.html

NIH Clinical Center Detailed Web Page

Other Identifiers

13-H-0051

Identifier Type: -

Identifier Source: secondary_id

130051

Identifier Type: -

Identifier Source: org_study_id