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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Yes
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Observational
Eligible Ages 30 Years and Over
Gender All
More Inclusion & Exclusion Criteria

For patients with sarcoidosis:

Inclusion Criteria:

  • - 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.

Exclusion Criteria:

  • - 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 - Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the subject ineligible for inclusion because of a safety concern For healthy volunteers:

    Inclusion criteria:

    - 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 - Normal predicted spirometry values: FEV1/FVC > 0.7 and FEV1 > 80% predicted - Healthy as determined by clinical history & examination by the investigator

    Exclusion criteria:

    - Inability to provide informed consent - Pregnancy - Patients with known chronic inflammation conditions such as rheumatoid arthritis, connective tissue disorders and inflammatory bowel disease - A significant cardiovascular event in the last 6 months - Insulin dependent diabetes mellitus or known impaired glucose tolerance - Participation in previous research trial in the last three years which involves exposure to significant ionising radiation (cumulative dose >10mSv) - 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 - Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the subject ineligible for inclusion because of a safety concern - Women of childbearing potential - Patients with known chronic infections such as HIV or known active tuberculosis.
- Active smoking history (defined as > than 1 cigarette per day on a regular basis) over lifetime - Known lung and/or respiratory disease or associated symptoms (e.g. dyspnoea, wheeze)

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03312712
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Cambridge University Hospitals NHS Foundation Trust
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Joseph Cheriyan, MBChB, MA, FRCP
Principal Investigator Affiliation Cambridge University Hospitals NHS Foundation Trust
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherIndustry
Overall Status Recruiting
Countries United Kingdom
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Lung Inflammation, Sarcoidosis
Additional Details

Inflammation plays an important role in a myriad of human diseases. Interstitial Lung Diseases (ILDs) are characterised by widespread inflammation and represent a major burden to the health sector. Imaging offers a method of assessing lung inflammation which is non-invasive and may help facilitate the development of new therapeutic drugs. Positron Emission Tomography (PET) is a sensitive imaging modality that uses radioactive material to highlight areas of disease. 18F-FDG is the most common radioactive tracer; it accumulates in cells with an increased metabolic rate. Previous studies have shown that inflammatory cells have an increased metabolic rate, thus PET imaging could highlight inflammation. 18F-FDG PET has been used in many studies exploring lung diseases; the concentration of tracer is thought to relate to the severity of inflammation. There is currently no standardised method to analyse FDG-PET scans to assess the concentration of tracer in the lung (and therefore inflammation). A major challenge is providing corrections to ensure that the image only represents tracer in the lung tissue. Such corrections are non-trivial and affect how images are interpreted. A robust validation is needed to ensure that the analysis methods used in FDG-PET images truly represent the degree of lung inflammation. Part A of this study aims to validate and compare the different analysis methods. Pulmonary sarcoidosis is a disease characterised by widespread lung inflammation. In Part A of the study the investigators will recruit patients with this condition, as well as age and gender matched (wherever possible) healthy volunteers. All Part A participants will receive one dynamic 18F-FDG PET/CT scan. The investigators will assess the uptake of 18FDG from PET images from patients with sarcoidosis versus those taken from healthy volunteers to validate and assess the reliability of the analysis method. For Part B of the study the investigators will recruit healthy volunteers aged 50 or more. If sarcoidosis patients in Part A are 50 years old or more, the age-matched HV will be recruited in to Part B instead, thus potentially minimising the number of HVs that might need to be recruited in to Part A of the study. The aims of this research study are: i) To compare FDG-PET derived tissue inflammation measures against measures of inflammation from BAL samples. ii) To compare different models of 18F-FDG lung analysis in patients with pulmonary sarcoidosis. iii) To identify whether FDG PET is sensitive enough to detect a change in inflammation induced in healthy volunteers.

Contact a Trial Team

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International Sites

Cambridge, United Kingdom

Status

Recruiting

Address

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , CB2 0QQ

Site Contact

Laurence Vass, MSc

ldv22@cam.ac.uk

01223 216895

Papworth Everard, United Kingdom

Status

Recruiting

Address

Royal Papworth Hospital NHS Foundation Trust

Papworth Everard, , CB23 3RE

Site Contact

Muhunthan Thillai, BA, PhD, MRCP

ldv22@cam.ac.uk

01223 216895

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