MRI in Cystic Fibrosis and Primary Ciliary Dyskinesia

A Pilot Study to Assess the Use of MRI in the Assessment of Patients With Cystic Fibrosis and Primary Ciliary Dyskinesia

This is a small pilot / feasibility study (Approximately 50 patients) to assess the possibility of clinical implementation of MRI assessment of patients with cystic fibrosis and primary ciliary dyskinesia.

Patients will undergo their standard CT imaging and lung function investigations and additionally will undergo MRI examination. Reports from CT (the current gold standard) and MRI will be assessed for concordance and patient acceptability and examination implementation costs will also be assessed. Novel MRI-based potential markers of CF and PCD disease state will also be assessed.

Study Overview

• Status: Unknown
• Conditions: Cystic Fibrosis; Primary Ciliary Dyskinesia
• Intervention / Treatment: Diagnostic test: MRI

Detailed Description

In this small single site pilot / feasibility study we aim to recruit approximately 50 patients over the age of 6 years with known cystic fibrosis (CF) or primary ciliary dyskinesia (PCD).

Patients will be recruited from routine clinic appointments or at admission for inpatient investigation and/or treatment at the point of referral for computed tomography (CT) examination. If they consent to participation they will undergo MRI examination in addition to their standard clinical CT (within 7 days of the CT scan - on the same day if practicable).

The magnetic resonance imaging (MRI) scans will be anonymised and reported by radiologists, blinded to the CT findings. The reports and scores (Eichinger and Brody2) will then be compared those of the standard CT to assess concordance between the modalities and inter and intra observer variability.

Potential novel biomarkers (pulmonary ventilation and perfusion (non-contrast) and sinus mucus and liver tissue characteristics) will be compared with established markers (including lung clearance index) and known CF mutation / PCD type.

Patients or their carers will also be asked to fill in a short questionnaire comparing the differential patient acceptability of CT and MRI examinations. The cost (time, resources etc) of each examination will be calculated and compared.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6NP
    • Recruiting
    • Royal Brompton Hospital
    • Contact: Anand Devaraj; Phone Number: 02073528121; Email: A.Devaraj@rbht.nhs.uk
    • Contact: Thomas Semple, FRCR MBBS; Phone Number: 02073528121; Email: T.Semple@rbht.nhs.uk
    • Principal Investigator: Anand Devaraj
    • Sub-Investigator: Simon Padley
    • Sub-Investigator: Thomas Semple

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with known cystic fibrosis or primary ciliary dyskinesia referred for CT chest as part of routine outpatient or inpatient investigations.

Description

Inclusion Criteria:

• Known CF or PCD Referred for CT chest

Exclusion Criteria:

• Contraindication to MRI (Pacemaker etc) Unable to stay still for MRI

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cystic fibrosis; Patients with known cystic fibrosis	Diagnostic test: MRI; MRI of lungs, paranasal sinuses and liver in addition to established clinical examinations (lung CT, pulmonary function testing); Other Names: Nuclear magnetic resonance (NMR)
Primary ciliary dyskinesia; Patients with known primary ciliary dyskinesia	Diagnostic test: MRI; MRI of lungs, paranasal sinuses and liver in addition to established clinical examinations (lung CT, pulmonary function testing); Other Names: Nuclear magnetic resonance (NMR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Structural and quantitative MRI vs CT in cystic fibrosis and primary ciliary dyskinesia assessment	To determine whether MRI with ventilation imaging can produce sufficiently diagnostic images, in the setting of CF or PCD, to replace CT imaging follow up. This will be assessed via semi-quantitative visual scoring (CT-based Brody / CFCT score and MRI-based Eichinger score) with both scoring systems applied to both CT and MRI. Scoring of the "air-trapping" component of CFCT will be substituted with scoring of ventilation defects on MRI. Scores will come from 2 observers, blinded to each others opinion, with a 3rd observer acting to resolve discrepancies. Intermodality variation will be assessed via ICC and Bland-Altman	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilation MRI vs Lung clearance index (LCI)	Dynamic oxygen enhanced MRI measures will be compared to equivalent measurements from lung clearance testing. Bland Altman and ICC analysis of time to oxygen wash in (in seconds) on MRI, to time to nitrogen washout in seconds from lung clearance testing	18 months
Sinus disease and exacerbations 1	Simple correlative statistics of degree of sinus opacification (percentage volume occupied by mucus and polyps) with frequency of infective exacerbations (number per month)	18 months
Sinus disease and exacerbations 2	Simple correlative statistics of degree of sinus opacification (percentage volume occupied by mucus and polyps) with rate of decline in spirometry measures (percentage drop in predicted FEV1 and FEV1/FVC over the 6 months prior to scanning)	18 months
Sinus disease and exacerbations 3	Simple correlative statistics of presence of susceptibility artefact in sinus mucus (binary; yes, no) with micro-organism cultured (nominal)	18 months
Liver disease 1	Simple correlation of liver volume (cm3) and T1 relaxation time (ms) with serologic markers of liver function (AST, ALT and ALP in IU/L and albumin in g/L)	18 months
Liver disease 2	Simple correlation of liver T1 relaxation time (ms) with ultrasound elastography markers of liver fibrosis (sheer wave speed in m/s)	18 months
Patient acceptability	To determine whether MRI is as acceptable to patients with CF or PCD as CT. This is via simple descriptive statistics from a bespoke questionnaire consisting of 5-point Likert scale questions regarding each scan.	18 months
Clinical implementation	To determine the operational cost differences in implementing MRI follow up vs CT follow up. Simple comparison of cost (in GBP) of diagnostic CT vs lung MRI.	18 months

Collaborators and Investigators

• Sponsor: Royal Brompton & Harefield NHS Foundation Trust
• Collaborators: University Hospital, Basel, Switzerland; Bioxydyn Ltd, Manchester
• Investigators: Principal Investigator: Anand Devaraj, Royal Brompton Hospital London

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2017
• Primary Completion (Anticipated): May 5, 2018
• Study Completion (Anticipated): May 5, 2018

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: September 11, 2017
• First Posted (Actual): September 12, 2017

Study Record Updates

• Last Update Posted (Actual): September 12, 2017
• Last Update Submitted That Met QC Criteria: September 11, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Lung MRI cystic fibrosis primary ciliary dyskinesia
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Lung Diseases; Neurologic Manifestations; Congenital Abnormalities; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Otorhinolaryngologic Diseases; Movement Disorders; Pancreatic Diseases; Abnormalities, Multiple; Ciliopathies; Fibrosis; Cystic Fibrosis; Dyskinesias; Ciliary Motility Disorders
• Other Study ID Numbers: 2016LI002B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share individual participant data outside the research team at this time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No