Bronchodilator Responsiveness in Obliterative Bronchiolitis (BD-OB)

This study has been completed.
Sponsor:
Information provided by:
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
ClinicalTrials.gov Identifier:
NCT01112241
First received: April 27, 2010
Last updated: February 28, 2011
Last verified: April 2010
  Purpose

This study has been designed to provide a substantial evidence of acute bronchodilator responsiveness to two sequentially inhaled drugs, a beta2-agonist (i.e., albuterol) and an anticholinergic (i.e., tiotropium bromide), in a group of patients who developed obliterative bronchiolitis after hematopoietic stem cell transplantation.


Condition Intervention Phase
Obliterative Bronchiolitis
Drug: albuterol plus tiotropium
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Acute Bronchodilator Responsiveness in Obliterative Bronchiolitis (OB) Following Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy:

Primary Outcome Measures:
  • Per Cent Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators [ Time Frame: Baseline and 90 min after bronchodilators ] [ Designated as safety issue: No ]
    Following albuterol plus tiotropium inhalation, FEV1 increments ≥12 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to the American Thoracic Society-European Respiratory Society standard criteria [Pellegrino et al. Eur Respir J 2005; 26: 948-968]. They were calculated as follows: [FEV1, expressed in liters (L), after bronchodilators - FEV1 (L) before bronchodilators/FEV1 (L) before bronchodilators x 100].

  • Absolute Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators [ Time Frame: Baseline and 90 min after bronchodilators ] [ Designated as safety issue: No ]
    Following albuterol plus tiotropium inhalation, FEV1 increments ≥0.20 liters (L) as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to the American Thoracic Society-European Respiratory Society standard criteria [Pellegrino et al. Eur Respir J 2005; 26: 948-968]. They were calculated as follows: [FEV1 (L) after bronchodilators - FEV1 (L) before bronchodilators].

  • Per Cent Change of Forced Vital Capacity (FVC) After Bronchodilators [ Time Frame: Baseline and 90 min after bronchodilators ] [ Designated as safety issue: No ]
    Following albuterol plus tiotropium inhalation, FVC increments ≥12 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to the American Thoracic Society-European Respiratory Society standard criteria [Pellegrino et al. Eur Respir J 2005; 26: 948-968]. They were calculated as follows: [FVC, expressed in liters (L), after bronchodilators - FVC (L) before bronchodilators/FVC (L) before bronchodilators x 100].

  • Absolute Change of Forced Vital Capacity (FVC) After Bronchodilators [ Time Frame: Baseline and 90 min after bronchodilators ] [ Designated as safety issue: No ]
    Following albuterol plus tiotropium inhalation, FVC increments ≥0.20 liters (L) compared with baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to the American Thoracic Society-European Respiratory Society standard criteria [Pellegrino et al. Eur Respir J 2005; 26: 948-968]. They were calculated as follows: [FVC (L) after bronchodilators - FVC (L) before bronchodilators].

  • Per Cent Change of Instantaneous Maximal Forced Expiratory Flow (V'Max) After Bronchodilators [ Time Frame: Baseline and 90 min after bronchodilators ] [ Designated as safety issue: No ]
    Following albuterol plus tiotropium inhalation, V'max increments ≥40 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to Pellegrino et al. [Chest 1998; 114:1607-1612]. They were calculated as follows: [V'max, expressed in liters.second-1 (L.s-1), after bronchodilators - V'max (L.s-1) before bronchodilators/V'max (L.s-1) before bronchodilators x 100].

  • Per Cent Change of Partial Forced Expiratory Flow (V'Part) After Bronchodilators [ Time Frame: Baseline and 90 min after bronchodilators ] [ Designated as safety issue: No ]
    Following albuterol plus tiotropium inhalation, V'part increments ≥40 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to Pellegrino et al. [Chest 1998; 114:1607-1612]. They were calculated as follows: [V'part, expressed in liters.second-1 (L.s-1), after bronchodilators - V'part (L.s-1) before bronchodilators/V'part (L.s-1) before bronchodilators x 100].

  • Per Cent Change of Residual Volume (RV) After Bronchodilators [ Time Frame: Baseline and 90 min after bronchodilators ] [ Designated as safety issue: No ]
    Following albuterol plus tiotropium inhalation, RV decrements ≥10 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to O'Donnell et al. [Eur Respir J 2001; 18: 914-920]. They were calculated as follows: [RV, expressed in liters (L), before bronchodilators - RV (L) after bronchodilators/RV (L) after bronchodilators x 100].

  • Absolute Change of Residual Volume (RV) After Bronchodilators [ Time Frame: Baseline and 90 min after bronchodilators ] [ Designated as safety issue: No ]
    Following albuterol plus tiotropium inhalation, RV decrements ≥0.30 liters (L) as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to O'Donnell et al. [Eur Respir J 2001; 18: 914-920]. They were calculated as follows: [RV (L), before bronchodilators - RV (L) after bronchodilators].

  • Per Cent Change of Functional Residual Capacity (FRC) After Bronchodilators [ Time Frame: Baseline and 90 min after bronchodilators ] [ Designated as safety issue: No ]
    Following albuterol plus tiotropium inhalation, FRC decrements ≥10 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to O'Donnell et al. [Eur Respir J 2001; 18: 914-920]. They were calculated as follows: [FRC, expressed in liters (L), before bronchodilators - FRC (L) after bronchodilators/FRC (L) after bronchodilators x 100].

  • Absolute Change of Functional Residual Capacity (FRC) After Bronchodilators [ Time Frame: Baseline and 90 min after bronchodilators ] [ Designated as safety issue: No ]
    Following albuterol plus tiotropium inhalation, FRC decrements ≥0.30 liters (L) as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to O'Donnell et al. [Eur Respir J 2001; 18: 914-920]. They were calculated as follows: [FRC (L), before bronchodilators - FRC (L) after bronchodilators].


Enrollment: 17
Study Start Date: April 2010
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: albuterol-tiotropium
At visit 1, lung function measurements will be performed in triplicate before and 90 min after inhaling four separate doses of 100 μg of albuterol (Ventolin®) and soon after 18 μg of tiotropium bromide [Spiriva®] to ensure maximal or near-maximal bronchodilation. Albuterol will be given by a metered-dose inhaler connected to a valved-holding chamber (Volumatic®) and tiotropium by a dry-powder device (Handihaler®).
Drug: albuterol plus tiotropium
Four separate doses of 100 μg of albuterol and 18 μg of tiotropium bromide. Albuterol will be given by a metered-dose inhaler connected to a valved-holding chamber and tiotropium by a dry-powder device.
Other Name: Ventolin® and Spiriva®

Detailed Description:

Obliterative bronchiolitis is a life-threatening non-infectious pulmonary complication of allogeneic hematopoietic stem cell transplantation (HSCT). It is characterized by the development of an obstructive abnormality which has been considered to be insensitive to bronchodilator treatments. However, this knowledge stems from measurements of forced expiratory volume in 1 s (FEV1) which is relatively insensitive to changes in small airway caliber. Moreover, it is known from studies in chronic obstructive pulmonary disease that symptoms improve after bronchodilator treatment even when FEV1 is minimally increased and correlate with the reduction of lung hyperinflation, which is the major consequence of severe expiratory airflow limitation. Therefore, measurements of airway caliber by parameters not affected by volume history and absolute lung volumes are preferable for assessing the effect of bronchodilator interventions.

In the current study, the bronchodilators responsiveness will be assessed by using not only spirometry but also measurements of absolute lung volumes and the forced expiratory flow of a partial maneuver (V'part) started from submaximal lung inflation, thus free of volume history effects.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Obliterative bronchiolitis (OB) following allogeneic HSCT
  • FEV1 to slow inspiratory vital capacity (VC) ratio (FEV1/VC)<5th percentile
  • FEV1 <75% predicted or absolute FEV1 fall >10% of pre-HSCT value
  • evidence of OB by computed tomography scanning
  • negative microbiological yields in bronchoalveolar lavage fluid
  • chronic graft-versus-host disease score >0
  • negative history for bronchial asthma, chronic obstructive pulmonary disease or other significant respiratory disease.

Exclusion Criteria:

  • inability to perform lung function maneuvers
  • pre-existent chronic lung disease other than OB
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01112241

Locations
Italy
Unit of Preventive and Occupational Medicine - Laboratory of Respiratory Pathophysiology, University Hospital San Martino
Genoa, Italy, 16132
Sponsors and Collaborators
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Investigators
Principal Investigator: Giovanni Barisione, MD Unit of Preventive and Occupational Medicine, University Hospital San Martino, Genoa, Italy
  More Information

Publications:
Responsible Party: Giovanni Barisione, Unit of Preventive and Occupational Medicine - Laboratory of Respiratory Pathophysiology
ClinicalTrials.gov Identifier: NCT01112241     History of Changes
Other Study ID Numbers: BOS-01
Study First Received: April 27, 2010
Results First Received: November 30, 2010
Last Updated: February 28, 2011
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy:
Obliterative bronchiolitis
Bronchodilator responsiveness
Partial forced expiratory flow
Lung volumes

Additional relevant MeSH terms:
Bronchiolitis
Bronchiolitis Obliterans
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Tiotropium
Albuterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents

ClinicalTrials.gov processed this record on October 02, 2014