Cryobiopsy Study to Assess Drug Distribution in Subjects With Suspected Interstitial Lung Disease

NCT03136120 | Completed

• 1 other identifier: 205053
• Study Type: observational
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Interstitial lung disease (ILD) often affects distal lung, and the evaluation of drug distribution to the relevant lung compartments is essential for development of new treatment options. This single center study will utilize samples obtained by transbronchial cryobiopsy (TBCB) procedure to assess the distribution of inhaled drugs in the lungs of the subjects with fibrotic lung disease using mass spectrometry techniques. The study will have a single visit and will include approximately 20 adult subjects with suspected fibrotic ILD and requiring TBCB as part of their diagnostic assessment. This will provide TBCB samples from up to 20 subjects, up to 5 of whom may also provide endobronchial forceps biopsy samples. The study will have 3 phases including screening to check the eligibility, biopsy phase in which all subjects will receive nebulized ipratropium bromide 500 microgram (mcg) for 10 minutes immediately before undergoing bronchoscopy and follow up phase from 7 to 14 days after the procedure. Drug distribution in the lung will be assessed by analyzing biopsy samples collected using mass spectrometry and imaging techniques.

Conditions

Lung Diseases, Interstitial

Keywords

Ipratropium bromide; Cryobiopsy; TBCB; IPF; Transbronchial cryobiopsy; Interstitial lung disease

Outcome Measures

Primary Outcomes (1)

• Evaluation of the distribution of ipratropium bromide within the cryobiopsy samples

  Images and data will be generated using mass spectrometric techniques and histology to show the distribution of ipratropium bromide within the lung cryobiopsy samples taken from subjects with suspected Interstitial Lung disease.

  Up to Week 4

Secondary Outcomes (2)

• Evaluation of the distribution of ipratropium bromide within the endobronchial sample

  Up to Week 4

• Distribution of ipratropium bromide in the proximal and distal lung

  Up to Week 4

Study Arms (1)

Subjects with suspected fibrotic ILD

Eligible subjects will receive nebulized ipratropium bromide 500 mcg for 10 minutes. The subjects will be sedated for bronchoscopic procedure as per routine practice for subjects having bronchoscopy. Cryobiopsy samples for this study will be taken after samples required for diagnosis has been taken and it is safe to do so. One to three endobronchial forceps biopsy samples will be taken from up to 5 subjects to allow comparison of proximal and distal drug distribution.

Drug: Ipratropium Bromide; Procedure: Flexible Bronchoscopy/Biopsy

Interventions

Ipratropium Bromide DRUG

Single dose of 500 mcg Ipratropium nebulizer solution will be administered to all subjects via inhalation route using nebulizer for 10 minutes. Ipratropium bromide is a clear, colorless nebulizer solution available in white plastic ampoules.

Subjects with suspected fibrotic ILD

Flexible Bronchoscopy/Biopsy PROCEDURE

After biopsy samples required for diagnosis have been collected, additional one to two TBCB samples will be taken for this study. 3-5 endobronchial biopsy samples will be taken from up to 5 subjects to compare drug distribution in proximal and distal lung.

Subjects with suspected fibrotic ILD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Male or female subjects above 18 years of age with suspected ILD referred for TBCB for clinical reasons, as part of their diagnostic work up, will be included in this study.

You may qualify if:

• and above years of age inclusive, at the time of signing the informed consent.
• Subjects with suspected ILD listed for TBCB for clinical reasons following review by the ILD services at University College London Hospitals (UCLH) in whom diagnosis has remained unclear following radiological and clinical assessment.

You may not qualify if:

• Male or Female.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions.
• Subjects who have a known drug allergy or other contra-indication to ipratropium bromide.
• Known hypersensitivity to atropine or ipratropium bromide or any other known drug allergies that, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation.
• As a result of the medical history, physical examination or screening investigations, the physician responsible considers the subject unfit for the study.
• The subject is unable or unwilling to perform study assessments and procedures correctly.
• Subjects with a recognized co-existing respiratory disorder (other than ILD) that in the opinion of the investigator would confound the study outcomes.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• University College London Hospitals: collaborator

Study Sites (1)

GSK Investigational Site

London, NW1 2PG, United Kingdom

Location

Related Publications (1)

• Mikolasch TA, Oballa E, Vahdati-Bolouri M, Jarvis E, Cui Y, Cahn A, Terry RL, Sahota J, Thakrar R, Marshall P, Porter JC. Mass spectrometry detection of inhaled drug in distal fibrotic lung. Respir Res. 2022 May 11;23(1):118. doi: 10.1186/s12931-022-02026-5.

  PMID: 35546672 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Lung biopsy samples collected from fibrotic regions of the lung using transbrochial cryobiopsy technique will be collected for this study. Endobronchial biopsy samples will also be taken. The samples will be embedded to a suitable polymer and frozen at -80 degree Celsius ready for analysis.

MeSH Terms

Conditions

Lung Diseases, Interstitial

Interventions

Ipratropium; Biopsy

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

• GSK Clinical Trials

  GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2017
• First Posted: May 2, 2017
• Study Start: November 21, 2017
• Primary Completion: November 13, 2018
• Study Completion: November 13, 2018
• Last Updated: January 29, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)