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

NCT01532024 | Completed Early Phase 1 DMC

• 2 other identifiers: NAP2011-006169-17
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief 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

Keywords

Optical Imaging; Neutrophil; Elastase; Molecular Imaging; Acute Lung Injury; ARDS

Outcome Measures

Primary Outcomes (1)

• This is an exploratory clinical study. The primary outcome measure is measurement of fluorescence and imaging parameters determined using pCLE and Cellvizio viewer software.

  Fluorescent amplification of NAP upon exposure to activated neutrophils in lungs of patients with Acute Lung Injury

  15 minutes

Secondary Outcomes (1)

• Safety in part A and part B and initial proof of concept in ICU to detect neutrophil activation.

  Within 24 hours of delivery of NAP

Study Arms (3)

Healthy Volunteers

EXPERIMENTAL

Delivery of intrapulmonary NAP Dose escalation from 5 mcgs to 80mcgs

Other: Microdose of NAP

Pulmonary Infiltrate in ICU

EXPERIMENTAL

Delivery of NAP (80mcgs) to ventilated patients with pulmonary infiltrates

Other: Microdose of NAP

Patients with Bronchiectasis

EXPERIMENTAL

Delivery of NAP (80mcgs) to patients with bronchiectasis

Other: Microdose of NAP

Interventions

Microdose of NAP OTHER

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

Healthy Volunteers; Patients with Bronchiectasis; Pulmonary Infiltrate in ICU

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• PART A: healthy male volunteers aged between 18 and 40.
• PART B: Ventilated patients over the age of 18 in on ITU with pulmonary infiltrate
• PART C: Male patients diagnosed with bronchiectasis over the age of 18

You may not qualify if:

• Age \< 18 or \>40 years
• History of any chronic or ongoing acute illness (with particular reference to asthma, upper respiratory tract infection, lower respiratory tract infection, bronchiectasis, congenital heart disease, ischaemic heart disease, valvular heart disease, diabetes mellitus, chronic renal impairment, urinary tract infection)
• Any current medication
• Any history of previous reactions to flourescein or any other anaphylaxis
• Abnormal physical signs detected at cardiorespiratory examination
• Temperature \>37.3 degrees Celsius
• Oxygen saturation \<95% breathing room air
• Haemoglobin, white cell count or platelet count outside the normal laboratory reference range
• Blood sodium, potassium, urea, creatinine, bilirubin, alanine aminotransferase, random glucose or C-reactive protein outside the normal laboratory reference range
• Forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) \<80% predicted
• FEV1:VC ratio \<70%
• Any significant cardiorespiratory abnormality detected on chest x-ray
• Peripheral venous access insufficient to support 14 gauge cannulae.
• General practitioner confirmation of eligibility as a healthy volunteer not received
• Failure to provide suitable identification (passport/driving licence)

Sponsors & Collaborators

• University of Edinburgh: lead
• Medical Research Council: collaborator

Study Sites (3)

Ward 118, Intensive Care, Royal Infirmary of Edinburgh

Edinburgh, Scotland, EH16 4TJ, United Kingdom

Location

Wellcome Trust Clinical Research Facility

Edinburgh, EH16 4SA, United Kingdom

Location

Royal Infirmary of Edinbrugh

Edinburgh, United Kingdom

Location

MeSH Terms

Conditions

Acute Lung Injury

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Kev Dhaliwal, MD

  University of Edinburgh

  STUDY DIRECTOR

• David Newby, MD

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

• Chris Haslett, MD

  University of Edinburgh

  STUDY CHAIR

• Tim Walsh, MD

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2012
• First Posted: February 13, 2012
• Study Start: October 1, 2014
• Primary Completion: September 2, 2016
• Study Completion: September 2, 2016
• Last Updated: November 5, 2019

Record last verified: 2019-11

Locations

GB (3)