Neutrophil Imaging in Healthy Subjects Following Lipopolysaccharide or Saline Challenge and in Subjects With Chronic Obstructive Pulmonary Disease

NCT02551614 | Completed Phase 1

• 1 other identifier: 201463
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

lipopolysaccharide; COPD; neutrophil

Outcome Measures

Primary Outcomes (4)

• Uptake of labelled neutrophils in the lung as assessed by single-photon emission tomography (SPECT).

  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.

  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 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 Outcomes (1)

• 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.

Study Arms (2)

Group 1: healthy subjects

EXPERIMENTAL

Subjects will undergo inhaled challenge, either with lipopolysaccharide or saline in a 2:1 ratio, prior to imaging assessments. Assessments will be performed during one study day on an outpatient basis.

Procedure: Lipopolysaccharide challenge; Procedure: Saline challenge; Procedure: Labelled neutrophils and Imaging assessment

Group 2: COPD patients

EXPERIMENTAL

Subjects will undergo imaging assessments during one study day on an outpatient basis. Approximately 10 of these COPD patients will repeat this study day 7-10 days after completion of the first study day to assess the reproducibility of the technique.

Procedure: Labelled neutrophils and Imaging assessment

Interventions

Lipopolysaccharide challenge PROCEDURE

Lipopolysaccharide solution inhaled using a dosimeter.

Group 1: healthy subjects

Saline challenge PROCEDURE

0.9% sodium chloride solution inhaled using dosimeter.

Group 1: healthy subjects

Labelled neutrophils and Imaging assessment PROCEDURE

Injection of labelled neutrophils and imaging assessments

Group 1: healthy subjects; Group 2: COPD patients

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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:

Sponsors & Collaborators

• GlaxoSmithKline: lead
• University of Cambridge: collaborator

Study Sites (2)

GSK Investigational Site

Cambridge, CB2 0QQ, United Kingdom

Location

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

Related Publications (1)

• Tregay N, Begg M, Cahn A, Farahi N, Povey K, Madhavan S, Simmonds R, Gillett D, Solanki C, Wong A, Maison J, Lennon M, Bradley G, Jarvis E, de Groot M, Wilson F, Babar J, Peters AM, Hessel EM, Chilvers ER. Use of autologous 99mTechnetium-labelled neutrophils to quantify lung neutrophil clearance in COPD. Thorax. 2019 Jul;74(7):659-666. doi: 10.1136/thoraxjnl-2018-212509. Epub 2019 Jan 23.

  PMID: 30674586 DERIVED

Related Links

• Results for study 201463 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2015
• First Posted: September 16, 2015
• Study Start: March 17, 2015
• Primary Completion: May 24, 2016
• Study Completion: May 24, 2016
• Last Updated: May 15, 2017

Record last verified: 2017-05

Locations

GB (2)