Exploratory Clinical Study of Neutrophil Activation Probe (NAP) for Optical Molecular Imaging in Human Lungs

Summary

Seriously ill patients may develop a complication called acute lung injury (ALI), a form of inflammation in which lung tissue is filled by fluid containing white blood cells called neutrophils. ALI is common and is often fatal (for example in the USA it is estimated that 190,000 patients develop ALI per annum, of whom 75,000 die). No pharmacological treatment has been shown to improve ALI.

Data from animal models and patients strongly suggest that neutrophils are central to disease progression. However no bedside methods exist to rapidly and accurately determine in seriously ill patients, if neutrophils are present and if they are releasing damaging enzymes such as elastase. As such, the investigating team have developed and synthesised to clinical grade, an imaging agent called NAP (Neutrophil Activation Probe) that detects activated neutrophils and also the damaging enzyme, human neutrophil elastase (HNE). The investigators have extensively tested NAP in animal models for efficacy and safety. It reliably detects activated neutrophils and is not toxic.

NAP is a small molecule that is delivered in tiny doses (called microdoses) to areas of inflammation in human lungs through a bronchoscope. The activity of NAP is visualised by imaging though a tiny camera that is also introduced through the bronchoscope. This camera system is now widely used throughout the world in over 150 sites.

The investigators therefore aim to test the utility and safety of NAP in an exploratory clinical study. The study involves the delivery of NAP to 6 healthy volunteers followed by delivering NAP to 3 patients in ICU with pulmonary infiltrates and 6 patients known to have bronchiectasis.

In the healthy volunteers study, healthy male volunteers recruited from the University of Edinburgh will be invited to participate.

In the ICU study, patients will be recruited from the ICU in the Royal Infirmary of Edinburgh.

In the bronchiectasis study, patients will be recruited from the respiratory service in NHS Lothian.

If the study (which is supported by the Medical Research Council) demonstrates safety and also the ability to image activated neutrophils, the investigators intention is to design future studies in patients with ALI.

Conditions

• Acute Lung Injury

Interventions

OTHER

Microdose of NAP

Delivery of NAP at microdose (\<100mcg) by direct pulmonary administration followed by fibreoptic confocal microendoscopy

Sponsors & Collaborators

• Medical Research Council

  collaborator OTHER_GOV

• University of Edinburgh

  lead OTHER

Principal Investigators

• Kev Dhaliwal, MD · University of Edinburgh

• David Newby, MD · University of Edinburgh

• Chris Haslett, MD · University of Edinburgh

• Tim Walsh, MD · University of Edinburgh

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-10-31

Primary Completion

2016-09-02

Completion

2016-09-02

Countries

• United Kingdom

Study Locations