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Pulmonary Disease, Chronic ObstructivePhase 1NCT02551614

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

A Phase 1 study testing Lipopolysaccharide challenge, Saline challenge and Labelled neutrophils and Imaging assessment in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 2 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 45 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Pulmonary Disease, Chronic Obstructive
What is being tested?
Lipopolysaccharide challenge, Saline challenge and Labelled neutrophils and Imaging assessment
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
2 sitesUnited Kingdom
Study dates
17 Mar 2015to 24 May 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • Group 1: healthy subjects
  • Alanine aminotranseferase (ALT) and bilirubin >1.5xupper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • QT corrected by Frederica's formula (QTcF) >450 millisecond (msec).
  • History of acute respiratory illnesses within 4 weeks prior to screening.
  • Asthma or history of asthma (including seasonal asthma).
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  • Oxygen saturation below 94% on room air.
  • Spirometry FEV1 <=80% of predicted or FEV1/FVC ratio <=70% at screening.
  • Ongoing treatment with statins that will be continued during the study or within two weeks of the first imaging visit.
  • History of regular alcohol consumption within 6 months of the study defined as: For United Kingdom sites: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (equivalent to 240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • History of sensitivity to the study challenge agent, radiochemicals, or components thereof, or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
  • Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid (RNA) polymerase chain reaction (PCR) test is obtained.
  • A positive pre-study smoking/drug/alcohol screen.
  • A positive test for human immunodeficiency virus antibody.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first imaging visit in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first imaging visit.
  • Previous exposure to ionising radiation above background (e.g. through work or research studies) that, combined with the estimated exposure dose to be given in this study, results in exposure over 10Milisievert (mSv) in a three year period. Clinical (therapeutic or diagnostic) exposures or those that involve patient benefit will not be included in this calculation.
  • Group 2: COPD patients
  • ALT and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • QTcF > 450 msec or QTcF > 480 msec in subjects with Bundle Branch Block
  • Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, pulmonary fibrosis, asthma or any other respiratory condition that might, in the opinion of the Investigator, compromise the safety of the or affect the interpretation of the results.
  • Any other concurrent inflammatory condition.
  • Anemia until adequately treated.
  • Ongoing treatment with monoclonal antibodies or treatment with monoclonal antibodies in the 12 months prior to the first imaging visit.
  • Ongoing treatment with systemic corticosteroids or systemic corticosteroids within 6 weeks prior to first imaging visit.
  • History of regular alcohol consumption within 6 months of the study defined as: For United Kingdom sites: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (equivalent to 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • History of sensitivity to the radiochemicals, or components thereof, or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
  • Presence of HBsAg, positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA PCR test is obtained.
  • A positive pre-study drug/alcohol screen.
  • A positive test for HIV antibody.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the imaging visit in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first imaging visit.
  • Previous exposure to ionising radiation above background through research studies or work that, combined with the estimated exposure dose to be given in this study, results in exposure over 10mSv in a three year period. Clinical (therapeutic or diagnostic) exposures or those that involve patient benefit will not be included in this calculation.

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • GSK Investigational Site

    Cambridge, CB2 0QQ

  • GSK Investigational Site

    Cambridge, CB2 2GG

Other trials in United Kingdom

About this study

Official title: Measurement of Neutrophil Retention in the Lung in Vivo, Using Autologous Labelled Neutrophils, in Healthy Subjects Following Lipopolysaccharide or Saline Challenge and Patients With Chronic Obstructive Pulmonary Disease (COPD)

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.

Being tested
Lipopolysaccharide challenge, Saline challenge, Labelled neutrophils and Imaging assessment
Keywords
lipopolysaccharide, COPD, neutrophil
Medical subject headings
Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lipopolysaccharide challengeProcedure or surgery

    Lipopolysaccharide solution inhaled using a dosimeter.

  • Saline challengeProcedure or surgery

    0.9% sodium chloride solution inhaled using dosimeter.

  • Labelled neutrophils and Imaging assessmentProcedure or surgery

    Injection of labelled neutrophils and imaging assessments

Study groups in NCT02551614
Study groupRoleWhat they receive
Group 1: healthy subjectsExperimentalSubjects 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.
Receives: Procedure: Lipopolysaccharide challenge; Procedure: Saline challenge; Procedure: Labelled neutrophils and Imaging assessment
Group 2: COPD patientsExperimentalSubjects 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.
Receives: Procedure: Labelled neutrophils and Imaging assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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.

  2. Comparison of neutrophil lung retention between saline-challenged and lipopolysaccharide -challenged healthy subjects.

    Measured: 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).

  3. Comparison of neutrophil lung retention between COPD patients and saline-challenged healthy subjects.

    Measured: 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.

  4. Comparison of neutrophil lung retention between COPD patients and lipopolysaccharide -challenged healthy subjects.

    Measured: 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)

  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.

    Uptake of labelled neutrophils in lungs will be assessed to investigate the reproducibility of the uptake of labelled neutrophils in subjects with stable COPD.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2015 (estimated)
  2. Study start17 Mar 2015
  3. Primary completion24 May 2016
  4. Study completion24 May 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02551614
Sponsor's protocol ID
201463
Status last verified
May 2017
First submitted
14 Sep 2015
Last updated
15 May 2017
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 30674586

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lipopolysaccharide challenge, Saline challenge and Labelled neutrophils and Imaging assessment in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 2 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Uptake of labelled neutrophils in the lung as assessed by single-photon emission tomography (SPECT). (time frame: 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.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02551614, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2017.

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