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Inhaled A1AT in Adult Stable Bronchiectasis

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ClinicalTrials.gov Identifier: NCT03383939
Recruitment Status : Completed
First Posted : December 27, 2017
Last Update Posted : December 27, 2017
Sponsor:
Collaborators:
Bayer
Sociedad Española de Neumología y Cirugía Torácica
Instituto de Salud Carlos III
Information provided by (Responsible Party):
Hospital Universitari Vall d'Hebron Research Institute

Brief Summary:

Aim: to investigate the influence of alpha1-antitrypsin (A1-AT) nebulization on levels of A1-AT in BAL and plasma in patients with stable bronchiectasis.

Method: single-blind placebo-controlled randomised clinical trial. 19 stable bronchiectasis patients with chronic bronchial infection and 10 control patients (without bronchiectasis) underwent a bronchoscopy in order to assess levels and inhibitory capacity of A1AT and neutrophilic elastase. Afterwards, the 19 bronchiectasis patients were randomly allocated to receive inhaled A1AT 250mg diluted in 10ml 0.9% saline solution once a day for a month (Group A, n: 10) or placebo (10ml 0.9% saline solution; group B, n: 9). A new BAL was performed in both groups (A and B) 24 hours after the end of treatment (1month) to re-analyze A1AT and NE.


Condition or disease Intervention/treatment Phase
Bronchiectasis Adult Drug: Group A Drug: Group B Not Applicable

Detailed Description:

Effects of inhaled alpha-1-anti-trypsin in bronchiectasis patients with chronic bronchial infection.

Introduction: one of the main features of bronchiectasis is chronic and deregulated neutrophilic bronchial inflammation. Excessive neutrophilic elastase (NE) activity has been widely described as part of the characteristic imbalance between proteases and anti-proteolytic enzymes that characterizes airways inflammation and progressive lung damage in bronchiectasis.

Alpha-1-antitrypsin (A1AT) is a protease inhibitor involved in protecting lung tissue from enzymes of inflammatory cells, including neutrophilic elastase, and its concentration rises in case of acute and chronic inflammation. Its reduction or absence is associated with the development of a specific kind of emphysema in case of exposure to tobacco smoking.

Moreover it is likely that its levels could be reduced in bronchiectasis as a consequence of chronic bronchial infection and inflammatory deregulation.

Aims:

  1. concentrations of total and free NE, NE inhibitory capacity and A1AT levels were investigated in broncho-alveolar lavage (BAL) of bronchiectasis patients with chronic airways infection in stable conditions in comparison with a control group (patients without bronchiectasis)
  2. The effects of inhaled A1AT (Prolastin) on BAL concentration of total and free NE and A1AT and inhibitory capacity of NE were assessed after one month of treatment in patients with bronchiectasis and chronic bronchial infection (placebo controlled trial) Study design: simple blind placebo-controlled randomized clinical trial

Methods:

19 patients with stable non cystic fibrosis bronchiectasis and chronic bronchial infection and 10 patients without bronchiectasis (control group) underwent a bronchoscopy to perform BAL analysis.

The 19 bronchiectasis patients were randomly allocated to receive inhaled A1AT 250mg diluted in 10ml 0.9% saline solution once a day for a month (Group A, n: 10) or placebo (10ml 0.9% saline solution; group B, n: 9). A new BAL was performed in both groups (A and B) 24 hours after the end of treatment (1month) to re-analyze A1AT and NE.

Clinical, microbiological, biochemical, functional and radiological characteristics of bronchiectasis and potential side effects of treatment on both arms were also recorded before (baseline), at 7, 15, 30 days of treatment and at 1 and 2 months follow-up visits after the end of treatment. The trial was approved by Spanish Ministry of Health (Trial nº 95/256) and local Ethics Committee (AC(HG) 44/95) and all patients signed written consent.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 2 parallel groups of patients with bronchictasis were investigated: 1 receiving inhaled prolastina and 1 receiving placebo (saline solution) all bronchiectasis patients were initially compared with 10 control patients with no bronchiectasis
Masking: Single (Investigator)
Primary Purpose: Supportive Care
Official Title: Effects of Inhaled Alpha-1-anti-trypsin on Proteolytic Activity in BAL of Bronchiectasis Patients With Chronic Bronchial Expectoration
Actual Study Start Date : June 1, 1996
Actual Primary Completion Date : September 7, 1999
Actual Study Completion Date : September 7, 1999

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: group A

10 patients randomly allocated received nebulised alpha1-antitrypsin 250mg (diluted in 10ml injectable solution) once a day during 1 month.

Intervention: nebulised alpha1-antitrypsin 250mg (diluted in 10ml injectable solution) once a day during 1 month

Drug: Group A
one nebulization with 250mg alpha-1-antitrypsine diluted in 10ml injectable solution once a day during 1 month. A CR-60 high flow compressor and Ventstream nebulizer were used for nebulization.
Other Name: inhaled Prolastin (nebulized alpha1-antitrypsin)

Placebo Comparator: group B

9 patients randomly allocated received 10ml 0.9%NaCl saline solution nebulised once daily during 1 month.

intervention: 10ml 0.9% Sodium Chloride saline solution nebulised once daily during 1 month.

Drug: Group B
10ml of 0.9% NaCl saline solution nebulised once daily for 1 month. A CR-60 high flow compressor and Ventstream nebulizer were used for nebulization.
Other Name: placebo

No Intervention: Control
10 patients without bronchiectasis were initially compared wiht bronchiectasis patients (group A + B) to define baseline levels of A1-AT and neutrophil elastase in BAL



Primary Outcome Measures :
  1. Changes from baseline BAL levels of A1AT [ Time Frame: 1 MONTH ]
    Changes from baseline in levels of A1AT in broncho-alveolar lavage at 1 month of treatment with inhaled A1AT


Secondary Outcome Measures :
  1. Changes from baseline neutrophil elastase in BAL [ Time Frame: 1 month ]
    Changes from baseline in levels of neutrophil elastase in broncho-alveolar lavage at 1 month of treatment with inhaled A1AT

  2. Changes from baseline neutrophil elastase inhibitory capacity in BAL [ Time Frame: 1 month ]
    Changes from baseline in levels of neutrophil elastase inhibitory capacity in broncho-alveolar lavage at 1 month of treatment with inhaled A1AT



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Stable clinical conditions (no use of systemic antibiotic or steroid treatment in the last month)
  • diagnosis of bronchiectasis bt CT scan
  • chronic purulent or mucopurulent expectoration (daily sputum expectoration in the last 6 months or more)

Exclusion Criteria:

  • Cystic fibrosis
  • interstitial lung disease as cause of bronchiectasis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03383939


Sponsors and Collaborators
Hospital Universitari Vall d'Hebron Research Institute
Bayer
Sociedad Española de Neumología y Cirugía Torácica
Instituto de Salud Carlos III
Investigators
Principal Investigator: Javier De Gracia, MD, PhD Servei de Pneumologia, Vall D'Hebron Hospital

Responsible Party: Hospital Universitari Vall d'Hebron Research Institute
ClinicalTrials.gov Identifier: NCT03383939     History of Changes
Other Study ID Numbers: AC(HG) 44/95
First Posted: December 27, 2017    Key Record Dates
Last Update Posted: December 27, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hospital Universitari Vall d'Hebron Research Institute:
bronchiectasis
alpha1-antitrypsin
neutrophilic elastase

Additional relevant MeSH terms:
Bronchiectasis
Bronchial Diseases
Respiratory Tract Diseases
Pharmaceutical Solutions
Alpha 1-Antitrypsin
Protein C Inhibitor
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action