Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
lipopolysaccharide, COPD, neutrophil
Brief summary
This is an exploratory study to further develop an imaging platform for the assessment of whole lung neutrophil retention. The primary objective of the study is to quantify and compare neutrophil retention in the lungs of lipopolysaccharide-challenged healthy subjects, saline-challenged healthy subjects and subjects with stable COPD. There will be two treatment groups, one with healthy subjects and the other with subjects with stable COPD. The total duration of this study for healthy subjects will be approximately 1 week, in addition to the screening window of 28 days. The total duration of this study for subjects with COPD will be approximately 1 week for those that complete Visit 1 only, and approximately 2 weeks for those subjects with COPD that return to the unit for Visit 2 7-10 days later, in addition to the screening window of 28 days.
Interventions
PROCEDURELipopolysaccharide challenge
Lipopolysaccharide solution inhaled using a dosimeter.
PROCEDURESaline challenge
0.9% sodium chloride solution inhaled using dosimeter.
PROCEDURELabelled neutrophils and Imaging assessment
Injection of labelled neutrophils and imaging assessments
Sponsors
University of Cambridge
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Group 1: Healthy subjects * Between 45 and 75 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring: A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. A subject with well-controlled hypertension, non-insulin dependent diabetes or other well controlled medical conditions may be included if the investigator, in consultation with the Medical Monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects must be stable on their current treatment for at least one month prior to first imaging visit. * Current non-smokers who have not used any tobacco products in the 6-month period preceding the screening visit and have a pack history of less than 5 pack years. Pack years = (cigarettes per day smoked/20) x number of years smoked) * Body weight \>=50 kilogram (kg) and body mass index (BMI) within the range 19-30 kg/meter (m)\^2 (inclusive). * Males. * A female subject is eligible to participate if she is not pregnant (as confirmed by a negative human chorionic gonadotrophin (hCG) test), not lactating, and of non reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Group 2: COPD patients * Between 45 and 75 years of age inclusive, at the time of signing the informed consent. * Stable stage 2-3 COPD patients, in accordance with the definition in the GOLD guidelines, 2014 and with forced expiratory volume in one second (FEV1) \>=40% predicted. Stable is defined as: No COPD exacerbations in the 3 months prior to first imaging visit. Subjects who are stable on their current treatment for at least one month prior to first imaging visit. * Body weight \>=45 kg and BMI within the range 18-32 kg/m\^2 (inclusive). * Males * A female subject is eligible to participate if she is not pregnant (as confirmed by a negative hCG test), not lactating, and of non reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with FSH and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels). Females on HRT and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Uptake of labelled neutrophils in the lung as assessed by single-photon emission tomography (SPECT). | Blood samples will be collected and imaging assessments will be completed after injection of labelled neutrophils at visit 1 (one day) for healthy subjects and visit 1 and 2 (upto two days, 10 days apart) for subjects with COPD. | Uptake of labelled neutrophils in lungs will be assessed to quantify neutrophil retention in the lungs of healthy subjects, lipopolysaccharide -challenged healthy subjects and subjects with stable COPD. |
| Comparison of neutrophil lung retention between saline-challenged and lipopolysaccharide -challenged healthy subjects. | Blood samples will be collected and imaging assessments will be completed after injection of labelled neutrophils at visit 1 (one day as an outpatient visit). | — |
| Comparison of neutrophil lung retention between COPD patients and saline-challenged healthy subjects. | Blood samples will be collected and imaging assessments will be completed after injection of labelled neutrophils at visit 1 (one day) for healthy subjects and visit 1 and 2 (upto two days, 10 days apart) for subjects with COPD. | — |
| Comparison of neutrophil lung retention between COPD patients and lipopolysaccharide -challenged healthy subjects. | Blood samples will be collected and imaging assessments will be completed after injection of labelled neutrophils at visit 1 (one day) for healthy subjects and visit 1 and 2 (upto two days, 10 days apart) for subjects with COPD. | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Uptake of neutrophils in the lung as assessed by SPECT analysis in stable COPD patients scanned on a second visit, 7-10 days after the first visit. | Blood samples will be collected and imaging assessments will be completed after injection of labelled neutrophils at visit 2 (upto two days as outpatient visits, upto 10 days apart) for subjects with COPD. | Uptake of labelled neutrophils in lungs will be assessed to investigate the reproducibility of the uptake of labelled neutrophils in subjects with stable COPD. |
Countries
United Kingdom
Outcome results
None listed