Functional Respiratory Imaging in Bronchiectasis

Bronchiectasis Clinical Trial

— FRIBE  

Official title:

Functional Respiratory Imaging During Pulmonary Exacerbations in Adults With Non-cystic Fibrosis Bronchiectasis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03818646
• Other study ID #: P02470
• Status: Not yet recruiting
• Start date: January 2019
• Est. completion date: April 2019

Study information

• Verified date: January 2019
• Source: Papworth Hospital NHS Foundation Trust
• Contact: Timothy Baird, MBBS
• Phone: 07706229153
• Email: tmbaird[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Four-week prospective single centre exploratory study in adults with bronchiectasis suffering a pulmonary exacerbation (defined as a change in one or more of the following: cough; sputum amount; sputum colour; breathlessness; fevers; and malaise).

The study will recruit ten adult subjects (male and female) who attend the Cambridge Centre for Lung Infection (CCLI) at the Royal Papworth Hospital, Cambridge, United Kingdom. The study will include individuals with a known diagnosis of bronchiectasis suffering a current pulmonary exacerbation. Participants seen during their usual clinic review with an exacerbation will be invited to participate and enrolled to commence the study that same day (day 0). Participants enrolled will undergo clinical review and a series of standard-of-care testing including sputum culture, lung function tests and blood analysis. Additional to these standard investigations, participants will also undertake a series of patient reported outcomes via validated respiratory questionnaires (Quality of Life - Bronchiectasis - QOL-B; & Leicester Cough Questionnaire - LCQ) and functional respiratory imaging (FRI). FRI consists of low dose high-resolution CT at full inspiration and expiration, combined with computational fluid dynamic testing.

Participants will be treated without delay according to standard of care treatment as per current international guidelines. Participants may be treated as either an inpatient or outpatient determined by the treating respiratory physician.

Follow up will occur on day 7, 14 and 28 post enrolment with serial CT imaging on days 0, 14 and 28. No scheduled follow up testing will be required beyond the day 28 visit, however all participants will receive a follow-up phone call at day 35.

The investigators hypothesize that changes in FRI parameters will be seen pre and post exacerbation treatment and will correlate with changes in lung function and patient reported outcomes. This will confirm FRI as a surrogate biomarker for assessing therapeutic response in future clinical trials in bronchiectasis.

Description:

Four-week prospective single centre exploratory study in adults with bronchiectasis suffering a pulmonary exacerbation.

The study will endeavour to recruit ten adult subjects (male and female) who attend the Cambridge Centre for Lung Infection (CCLI) at the Royal Papworth Hospital, Cambridge, United Kingdom. The study will include individuals with a known diagnosis of bronchiectasis (defined as symptoms of chronic or recurrent bronchial infection with radiological evidence of abnormal and permanent dilation of bronchi) not from cystic fibrosis; and a current pulmonary exacerbation (defined as a 'deterioration in three or more of the following key symptoms for at least 48h: cough; sputum volume and/or consistency; sputum purulence; breathlessness and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND that a clinician determines a change in bronchiectasis treatment is required).

In order to maximise subject recruitment and understanding of the study, all CCLI patients with bronchiectasis that are known to suffer frequent exacerbations (>2 per year) will be sent details of the trial including the Patient Information and Consent Form at the time of study commencement, prior to their individual enrolment. Subjects then seen during their usual clinic review with a pulmonary exacerbation will be invited to participate and enrolled to commence the study that same day (day 0). Participants enrolled will undergo clinical review and a series of standard testing including pulmonary function tests and blood analysis. Additional to these standard investigations, participants will also undertake a series of patient reported outcomes via validated respiratory questionnaires (Quality of Life

• Bronchiectasis - QOL-B; & Leicester Cough Questionnaire - LCQ) and functional respiratory imaging (FRI). FRI consists of low dose high-resolution CT at total lung capacity (TLC) and functional residual capacity (FRC), combined with computational fluid dynamic testing (CFD).

Participants will be treated without delay according to standard usual care as per the current European Respiratory Society (ERS) and British Thoracic Society (BTS) Bronchiectasis Guidelines. Participants may be treated as either an inpatient or outpatient determined by the treating consultant respiratory physician.

Follow up will occur on day 7, 14 and 28 post enrolment. Participants will undergo clinical review and repeat testing according to the below schedule. No scheduled follow up testing will be required beyond the day 28 visit, however all participants will receive a follow up phone call at day 35.

Day 0: Initial consultation - presentation with a pulmonary exacerbation

• Recruitment, consent and enrolment

• History and clinical examination

• Bloods (WCC; neutrophil count; CRP)

• Pregnancy test (urine dipstick) - if appropriate

• Lung function testing (FEV1; FVC; TLC)

• Sputum collection

• Functional respiratory imaging (HRCT at TLC and FRC; may occur + 48 hours of enrolment)

• Patient reported outcomes / questionnaires (QOL-B; LCQ)

• Usual treatment commencement (as per current bronchiectasis guidelines)

Day 7: Mid-treatment follow up (as per usual standard of care)

• History and clinical review

• Bloods (WCC, neutrophil count; CRP)

Day 14: End of treatment follow up

• History and clinical examination

• Bloods (WCC; neutrophil count; CRP)

• Pregnancy test (urine dipstick) - if appropriate

• Lung function testing (FEV1; FVC; TLC)

• Functional respiratory imaging (HRCT at TLC and FRC; may occur +/- 48 hours of day 14)

• Patient reported outcomes / questionnaires (QOL-B; LCQ)

Day 28: Completion of study testing

• History and clinical examination

• Bloods (WCC; neutrophil count; CRP)

• Pregnancy test (urine dipstick) - if appropriate

• Lung function testing (FEV1; FVC; TLC)

• Functional respiratory imaging (HRCT at TLC and FRC; may occur +/- 48 hours of day 28)

• Patient reported outcomes (QOL-B; LCQ)

Day 35: Phone call by research team member

• No scheduled investigations

No scheduled follow up testing will be required beyond the day 28 visit other then a follow up phone call at day 35 (see above).

The investigators hypothesize that changes in FRI parameters will be seen pre and post exacerbation treatment and will correlate well with changes in lung function and patient reported outcomes. This will confirm FRI as a surrogate biomarker for assessing therapeutic response in future clinical trials in bronchiectasis.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: April 2019
• Est. primary completion date: April 2019
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Adult male and females =18 years and = 80 years

• Current diagnosis of bronchiectasis (see above definition)

• Current pulmonary exacerbation (see above definition)

Exclusion Criteria:

• Severe obstructive airways disease (defined as FEV1 < 30%; FEV1/FVC < 70%)

• Diagnosis of other active chronic lung disease (asthma; ABPA; COPD; pulmonary fibrosis)

• Currently treated non-tuberculous mycobacterial disease

• Acute congestive cardiac failure

• Contra-indication or unable to perform HRCT imaging, including pregnancy

• Contra-indication or unable to perform pulmonary function testing

• Active lung malignancy

Related Conditions & MeSH terms

• Bronchiectasis

Intervention

Diagnostic Test:
• Functional Respiratory Imaging
Functional Respiratory Imaging (FRI) is a novel image based functional diagnostic tool that combines high-resolution CT scans (HRCT) at TLC and FRC with flow simulations (computational fluid dynamics - CFD) providing a 3D visualization and quantification of lung structure and function.

Locations

Country	Name	City	State
United Kingdom	Royal Papworth Hospital NHS Foundation Trust	Papworth Everard	Cambridgeshire

Sponsors (1)

Lead Sponsor	Collaborator
Papworth Hospital NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (12)

Bos AC, van Holsbeke C, de Backer JW, van Westreenen M, Janssens HM, Vos WG, Tiddens HA. Patient-specific modeling of regional antibiotic concentration levels in airways of patients with cystic fibrosis: are we dosing high enough? PLoS One. 2015 Mar 3;10(3):e0118454. doi: 10.1371/journal.pone.0118454. eCollection 2015. — View Citation

Chang AB, Bell SC, Byrnes CA, Grimwood K, Holmes PW, King PT, Kolbe J, Landau LI, Maguire GP, McDonald MI, Reid DW, Thien FC, Torzillo PJ. Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand. Med J Aust. 2010 Sep 20;193(6):356-65. — View Citation

De Backer LA, Vos W, De Backer J, Van Holsbeke C, Vinchurkar S, De Backer W. The acute effect of budesonide/formoterol in COPD: a multi-slice computed tomography and lung function study. Eur Respir J. 2012 Aug;40(2):298-305. doi: 10.1183/09031936.00072511. Epub 2011 Dec 19. — View Citation

Hajian B, De Backer J, Vos W, Van Holsbeke C, Clukers J, De Backer W. Functional respiratory imaging (FRI) for optimizing therapy development and patient care. Expert Rev Respir Med. 2016 Feb;10(2):193-206. doi: 10.1586/17476348.2016.1136216. Review. — View Citation

Hill AT, Haworth CS, Aliberti S, Barker A, Blasi F, Boersma W, Chalmers JD, De Soyza A, Dimakou K, Elborn JS, Feldman C, Flume P, Goeminne PC, Loebinger MR, Menendez R, Morgan L, Murris M, Polverino E, Quittner A, Ringshausen FC, Tino G, Torres A, Vendrell M, Welte T, Wilson R, Wong C, O'Donnell A, Aksamit T; EMBARC/BRR definitions working group. Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research. Eur Respir J. 2017 Jun 8;49(6). pii: 1700051. doi: 10.1183/13993003.00051-2017. Print 2017 Jun. — View Citation

Koser U, Hill A. What's new in the management of adult bronchiectasis? F1000Res. 2017 Apr 20;6:527. doi: 10.12688/f1000research.10613.1. eCollection 2017. Review. — View Citation

Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58. doi: 10.1136/thx.2010.136119. Review. — View Citation

Polverino E, Goeminne PC, McDonnell MJ, Aliberti S, Marshall SE, Loebinger MR, Murris M, Cantón R, Torres A, Dimakou K, De Soyza A, Hill AT, Haworth CS, Vendrell M, Ringshausen FC, Subotic D, Wilson R, Vilaró J, Stallberg B, Welte T, Rohde G, Blasi F, Elborn S, Almagro M, Timothy A, Ruddy T, Tonia T, Rigau D, Chalmers JD. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J. 2017 Sep 9;50(3). pii: 1700629. doi: 10.1183/13993003.00629-2017. Print 2017 Sep. — View Citation

Quint JK, Millett ER, Joshi M, Navaratnam V, Thomas SL, Hurst JR, Smeeth L, Brown JS. Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study. Eur Respir J. 2016 Jan;47(1):186-93. doi: 10.1183/13993003.01033-2015. Epub 2015 Nov 5. — View Citation

van Geffen WH, Hajian B, Vos W, De Backer J, Cahn A, Usmani OS, Van Holsbeke C, Pistolesi M, Kerstjens HA, De Backer W. Functional respiratory imaging: heterogeneity of acute exacerbations of COPD. Int J Chron Obstruct Pulmon Dis. 2018 May 30;13:1783-1792. doi: 10.2147/COPD.S152463. eCollection 2018. — View Citation

Vendrell M, de Gracia J, Olveira C, Martinez-Garcia MA, Girón R, Máiz L, Cantón R, Coll R, Escribano A, Solé A. [Diagnosis and treatment of bronchiectasis. Spanish Society of Pneumology and Thoracic Surgery]. Arch Bronconeumol. 2008 Nov;44(11):629-40. Spanish. — View Citation

Vos W, De Backer J, Poli G, De Volder A, Ghys L, Van Holsbeke C, Vinchurkar S, De Backer L, De Backer W. Novel functional imaging of changes in small airways of patients treated with extrafine beclomethasone/formoterol. Respiration. 2013;86(5):393-401. doi: 10.1159/000347120. Epub 2013 Apr 12. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Airway volume	Change in image based airway volume from FRI	Days 0; 14; and 28
Primary	Airway resistance	Change in image based airway resistance from FRI	Days 0; 14; and 28
Primary	Lung volume	Change in image based lung volume from FRI	Days 0; 14; and 28
Primary	Internal airflow distribution	Change in image based internal airflow distribution from FRI	Days 0; 14; and 28
Primary	Airway wall thickness	Change in image based airway wall thickness from FRI	Days 0;14; and 28
Primary	Blood vessel density	Change in image based blood vessel density from FRI	Days 0; 14; and 28
Primary	Centreline evaluation (airway dimensions over distance into the lung).	Change in image based centreline evaluation (airway dimensions over distance into the lung) from FRI	Days 0; 14; and 28
Secondary	Lung function	Correlation of FRI to lung function (FEV1)	Days 0; 14; and 28
Secondary	QOL-B	Correlation of FRI to the QOL-B (Quality of Life Bronchiectasis) questionnaire	Days 0; 14; and 28
Secondary	LCQ	Correlation of FRI to the LCQ (Leicester Cough Questionnaire) questionnaire	Days 0; 14; and 28
Secondary	CRP	Correlation of FRI to CRP (C-reactive protein)	Days 0; 14; and 28