Nebulized or Inhaled Albuterol for Lymphangioleiomyomatosis

Overview

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.

Full Title of Study: “13-H-0051 Bronchodilator Effects of Nebulized Versus Inhaled Albuterol in Subjects With Lymphangioleiomyomatosis”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 1, 2022

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.

Interventions

  • Drug: albuterol inhaler
    • 2 puffs of Metered Dose inhaler for Bronchodilation
  • Drug: albuterol nebulizer
    • Albuterol administered by nebulization will produce a greater increase in FEV1.
  • Procedure: PFT
    • Breathing Test

Arms, Groups and Cohorts

  • Experimental: 1
    • Nebullizer
  • Active Comparator: 2
    • Inhaler

Clinical Trial Outcome Measures

Primary Measures

  • Greater improvement in lung function with nebulized albuterol.
    • Time Frame: 3 days
    • Greater improvement in lung function with nebulized albuterol.

Participating in This Clinical Trial

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).

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • National Heart, Lung, and Blood Institute (NHLBI)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Joel Moss, M.D., Principal Investigator, National Heart, Lung, and Blood Institute (NHLBI)
  • Overall Contact(s)
    • Tatyana Worthy, R.N., (301) 827-1376, worthyt@mail.nih.gov

References

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

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. Epub 2005 Oct 6.

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.

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