Clinical trial NCT00001462: Characterization of the Pathobiology of Early Lung Destruction in Alpha 1-Antitrypsin Deficient Individuals
Official title: Characterization of the Pathobiology of Early Lung Destruction in Alpha 1-Antitrypsin Deficient Individuals
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Emphysema
Lung Diseases, Obstructive
Alpha 1-Antitrypsin Deficiency
Keywords: Alpha 1-Antitrypsin Deficiency
Emphysema
Genetic Diseases
Inflammation
Nitric Oxide
Protease
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2002-12-10
Enrollment: 60
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes

Brief summary: Alpha 1-antitrypsin-deficient individuals develop severe destructive lung disease much earlier and their lung function declines faster than the general population of individuals with chronic obstructive lung disease. This study is designed to better understand the pathogenesis of lung destruction in alpha 1-antitrypsin deficient individuals and to characterize the pathobiology of early lung destruction. To accomplish this we intend to use bronchoalveolar lavage to determine and quantify the factors that initiate and sustain lung inflammation in alpha 1-antitrypsin deficient individuals with lung function above a force expiratory volume in one second (FEV1) of greater than 50% of predicted.

Detailed description: Alpha 1-antitrypsin-deficient individuals develop severe destructive lung disease much earlier and their lung function declines faster than the general population of individuals with chronic obstructive lung disease. This study is designed to better understand the pathogenesis of lung destruction in alpha 1-antitrypsin deficient individuals and to characterize the pathobiology of early lung destruction. To accomplish this we intend to use bronchoalveolar lavage to determine and quantify the factors that initiate and sustain lung inflammation in alpha 1-antitrypsin deficient individuals with lung function above a force expiratory volume in one second (FEV1) of greater than 50% of predicted.

Eligibility criteria: Any alpha 1 antitrypsin-deficient individuals.

18-65 years old.

FEV1 greater than 1 equal to 50 percent of predicted (forced expiratory volume).

Study participation is required for one year.

A total of four bronchoscopies will be performed over a year period.

Methacholine challenge test will be performed at the beginning and end of the study to assess the degree of reactive airways disease.

Pneumococcal and annual influenza vaccine will be given.

No prolastin within one year prior to start of the study.

No oral systemic corticosteroids within 30 days prior to start of study.

No allergy to topical or local anesthetic (i.e., lidocaine).

No pregnancy.

No HIV positive patients.

No Hepatitis B/C virus positive patients.

No patients with any condition associated with immunodeficiency.

No patients with presence of significant cardiac diseases.

No patients with presence of uncorrected blood-clotting disorders.

No patients with any oxygen at home on a regular basis.

No adverse reactions to methacholine.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Heart, Lung and Blood Institute (NHLBI)
state: Maryland
Study officials:
References:
citation: Buist AS. Alpha 1-antitrypsin deficiency in lung and liver disease. Hosp Pract (Off Ed). 1989 May 15;24(5):51-9. doi: 10.1080/21548331.1989.11703712. No abstract available.
citation: Crystal RG. Alpha 1-antitrypsin deficiency, emphysema, and liver disease. Genetic basis and strategies for therapy. J Clin Invest. 1990 May;85(5):1343-52. doi: 10.1172/JCI114578. No abstract available.
citation: Gadek JE, Pacht ER. The protease-antiprotease balance within the human lung: implications for the pathogenesis of emphysema. Lung. 1990;168 Suppl:552-64. doi: 10.1007/BF02718178.
citation: Paris AE, Vragovic O, Sonalkar S, Finneseth M, Borgatta L. Mifepristone and misoprostol compared to osmotic dilators for cervical preparation prior to surgical abortion at 15-18 weeks' gestation: a randomised controlled non-inferiority trial. BMJ Sex Reprod Health. 2019 Nov 21:bmjsrh-2019-200367. doi: 10.1136/bmjsrh-2019-200367. Online ahead of print.