Validation of the Analysis Methodology Behind the Use of Quantitative 18F-FDG PET/CT to Assess Lung Inflammation

NCT03312712 | Unknown

• 1 other identifier: VERIFY
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to validate the method of analysing Positron Emission Tomography (PET) images to assess lung inflammation. Development of novel therapeutic drugs requires a biomarker which is sensitive to the underlying disease and can respond to therapeutic interventions. PET is a potential imaging biomarker which can target molecular and cellular processes. There is currently no standardised method of analysing PET lung data and a lack of validation for the existing techniques. This study is divided in to two parts. Part A aims to determine the best method to perform 18F-FDG PET/CT lung analysis and how it correlates with cell counts from bronchoalveolar lavage (BAL) samples taken from participants with active pulmonary sarcoidosis. Part B will compare imaging data from healthy volunteers who have either undergone a Lipopolysaccharide (LPS) challenge (whereby the lung is temporarily inflamed) or saline equivalent to determine whether lung inflammation can be detected by 18F-FDG PET/CT. No medications will be given and patients will not be asked to stop or change existing medication.

Conditions

Lung Inflammation; Sarcoidosis

Keywords

FDG; PET; CT; Sarcoidosis

Outcome Measures

Primary Outcomes (1)

• Validation of 18F-FDG methodology used to assess lung inflammation in participants with sarcoidosis

  18F-FDG will be assessed using Patlak analysis and a compartmental model. This will be validated against histological samples from lung biopsies taken as part of the patient's standard clinical care prior to enrolling on to this study, and the inflammatory cell counts and densities (principally of macrophages and neutrophils) from BAL fluid in sarcoidosis patients.

  Up to 4 weeks

Secondary Outcomes (5)

• Pulmonary function tests

  Screening Visit (V1)

• Pulmonary function tests

  Screening Visit (V1)

• Plasma biomarkers of inflammation

  Up to 4 weeks

• Plasma biomarkers of inflammation

  Up to 4 weeks

• Leukocyte count and activity from BAL fluid samples

  Up to 6 weeks

Study Arms (2)

Participants with sarcoidosis

* Bronchoscopy, BAL collection, and PFTs\* \[SoC\] \*if required * Screening, research and safety bloods * Dynamic 18F-FDG PET/CT scan

Radiation: PET/CT scan; Diagnostic Test: Blood and urine sampling

Healthy volunteers

Part A: * PFTs * Screening, research and safety bloods * Dynamic 18F-FDG PET/CT scan Part B: * PFTs * Screening, research and safety bloods * Baseline and post challenge Dynamic 18F-FDG PET/CT scans * LPS/saline challenge

Radiation: PET/CT scan; Other: LPS Challenge; Other: Saline Challenge; Diagnostic Test: Blood and urine sampling

Interventions

PET/CT scan RADIATION

PET/CT will be performed at Cambridge University Hospital's PET-CT unit, Cambridge. Participants in Part A of the study (sarcoidosis and HVs) will receive one PET/CT scan. A Cine-CT scan will be performed immediately prior to the 18F-FDG PET/CT scan. Settings for the CT scans will be determined by clinical protocols, radiation dose will be kept as low as reasonably practicable (ALARP) consistent with UK legislation. After 6 hours of fasting and if blood glucose concentration is ≤11mmol/L participants will proceed to undergo an 18FDG PET/CT scan. 18F-FDG will be administered intravenously at a dose of approximately 200 MBq. Positron emission scanning will involve a 60-minute dynamic acquisition from the lungs.

Healthy volunteers; Participants with sarcoidosis

LPS Challenge OTHER

In Part B, eight healthy volunteers will undergo an LPS challenge whereby each participant is injected with the challenge agent, Lipopolysaccharide (LPS), to invoke temporary mild lung inflammation. Each participant will have a PET/CT scan before and after the administration of LPS and the images will be assessed to determine whether these methods are able to detect true lung inflammation.

Healthy volunteers

Saline Challenge OTHER

In Part B, four healthy volunteers will undergo a saline challenge as outlined above for the LPS challenge. Pre- and post-challenge scans will provide control data for the study.

Healthy volunteers

Blood and urine sampling DIAGNOSTIC_TEST

For women whose post-menopausal status and/or pregnancy status is uncertain at screening, a blood sample will be collected to test for pregnancy and menopausal status (hormone profiling) before enrolling them on to the study. If pregnancy status is still uncertain at study visits, participants will have a urine pregnancy test before undergoing any PET/CT scans to ensure it is safe for them to continue in the study.

Healthy volunteers; Participants with sarcoidosis

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Cohort 1: Participants with suspected pulmonary sarcoidosis Cohort 2: Healthy volunteers who are non-smokers, age and gender matched, where possible, to cohort 1 participants

You may qualify if:

• Suspected pulmonary sarcoidosis (as determined by referring physician)
• Requires bronchoscopy, EBUS and BAL (as determined by ILD team at Royal Papworth or Addenbrooke's Hospitals).
• Male or female ≥ 30 years with a BMI of 17-35kg/m2
• Consents to additional bronchoscopic evaluation during NHS mandated bronchoscopy, EBUS and BAL.

You may not qualify if:

• Inability to provide Informed Consent.
• A cardiovascular event in the last 6 months (i.e. acute coronary syndrome, unstable angina, CABG, PCI, stroke, MI, carotid endarterectomy).
• Patients with known clinically significant pulmonary diagnoses of COPD, lung fibrosis, interstitial lung disease, or α1-antitrypsin deficiency.
• Active smoking during the last 5 years.
• Patients with known chronic infections such as HIV or known active tuberculosis.
• Patients with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with active chronic inflammation (e.g. Inflammatory Bowel Disease).
• Known diabetes mellitus or known impaired glucose tolerance
• Participation in a previous research trial in the last three years which involved exposure to significant ionising radiation (i.e. cumulative research radiation dose \>10 mSv)
• Pregnancy
• Women of childbearing potential \[i.e. either postmenopausal or documented hysterectomy and/or bilateral oophorectomy - tubal ligation is not sufficient\].
• Use of systemic steroids (oral or intravenous) at a dose \> 10mg od of prednisolone or equivalent and/or antibiotics 4 weeks prior to PET/CT scan
• For healthy volunteers:
• Age/gender-matched group (Part A only): Male or female ≥ 30 years with a BMI of 17-35kg/m2 inclusive
• LPS/saline challenge group (Part B only): Male or female ≥ 50 years with a BMI of 17-35kg/m2 inclusive
• No smoking history

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• GlaxoSmithKline: collaborator

Study Sites (2)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Royal Papworth Hospital NHS Foundation Trust

Papworth Everard, CB23 3RE, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Venous blood samples and Bronchoalveolar lavage (fluid taken as part of sarcoidosis patient standard of care bronchoscopy at Papworth Hospital) will be analysed at either Cambridge University Hospitals or Papworth Hospital. Research specific venous blood and urine samples will be also obtained, where applicable, as per the study protocol for all participants.

MeSH Terms

Conditions

Pneumonia; Sarcoidosis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Joseph Cheriyan, MBChB, MA, FRCP

  Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laurence Vass

CONTACT

01223 216895; ldv22@cam.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Clinical Pharmacologist & Physician/Associate Lecturer

Study Record Dates

• First Submitted: October 9, 2017
• First Posted: October 18, 2017
• Study Start: January 23, 2018
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: January 9, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)