Inhaled A1AT in Adult Stable Bronchiectasis

Brief Title

Inhaled A1AT in Adult Stable Bronchiectasis

Official Title

Effects of Inhaled Alpha-1-anti-trypsin on Proteolytic Activity in BAL of Bronchiectasis Patients With Chronic Bronchial Expectoration

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.
    

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

Primary Outcome

Changes from baseline BAL levels of A1AT

Secondary Outcome

 Changes from baseline neutrophil elastase in BAL

Condition

Bronchiectasis Adult

Intervention

Group A

Study Arms / Comparison Groups

 group A

Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

20

Start Date

June 1, 1996

Completion Date

September 7, 1999

Primary Completion Date

September 7, 1999

Eligibility 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
      

Gender

All

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

Javier De Gracia, MD, PhD, , 

NCT ID

NCT03383939

Organization ID

AC(HG) 44/95

Responsible Party

Sponsor

Study Sponsor

Hospital Universitari Vall d'Hebron Research Institute

Collaborators

 Bayer

Study Sponsor

Javier De Gracia, MD, PhD, Principal Investigator, Servei de Pneumologia, Vall D'Hebron Hospital

Verification Date

December 2017