Acute Lung Injury Clinical Trial
— NAPOfficial title:
Phase 1 Exploratory Clinical Study of Microdosing NAP for Optical Molecular Imaging in Human Lungs in Healthy Volunteers and in Patients With Acute Lung Injury in Intensive Care
Verified date | November 2019 |
Source | University of Edinburgh |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 15 |
Est. completion date | September 2, 2016 |
Est. primary completion date | September 2, 2016 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Male |
Age group | 18 Years to 60 Years |
Eligibility |
Inclusion Criteria: - 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 Exclusion criteria for part A: 1. Age < 18 or >40 years 2. 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) 3. Any current medication 4. Any history of previous reactions to flourescein or any other anaphylaxis 5. Abnormal physical signs detected at cardiorespiratory examination 6. Temperature >37.3 degrees Celsius 7. Oxygen saturation <95% breathing room air 8. Haemoglobin, white cell count or platelet count outside the normal laboratory reference range 9. Blood sodium, potassium, urea, creatinine, bilirubin, alanine aminotransferase, random glucose or C-reactive protein outside the normal laboratory reference range 10. Forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) <80% predicted 11. FEV1:VC ratio <70% 12. Any significant cardiorespiratory abnormality detected on chest x-ray 13. Peripheral venous access insufficient to support 14 gauge cannulae. 14. General practitioner confirmation of eligibility as a healthy volunteer not received 15. Failure to provide suitable identification (passport/driving licence) 16. Refusal to consent to enter details in 'The Over Volunteering Prevention System' (TOPS) database 17. Positive urine drug screen 18. Participation in any other interventional study or less than three months since their last participation in an interventional study 19. Female Exclusion Criteria for part B 1. Age <18years 2. Any contraindication for bronchoscopy 22,23 3. Refusal for participation by attending consultant 4. Fi02 >70% 5. PEEP>10cm 6. Recent pneumothorax (whilst on ventilator) 7. Any history of previous reactions to flourescein or any other anaphylaxis 8. Participation in any other interventional study or less than three months since their last participation in an interventional study 9. Female Exclusion criteria for Part C 1. Age <18years 2. Any contraindication with bronchoscopy 3. Refusal for aprticipation by attending consultant 4. Recent pneumothorax (last 4 weeks) 5. Myocardial infarction within preceding 4 weeks 6. Any history of previous reactions to fluorescein or any other anaphylaxis 7. Participation in any other interventional study or less than three months since their last participation in an interventional study. 8. Female |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Royal Infirmary of Edinbrugh | Edinburgh | |
United Kingdom | Ward 118, Intensive Care, Royal Infirmary of Edinburgh | Edinburgh | Scotland |
United Kingdom | Wellcome Trust Clinical Research Facility | Edinburgh |
Lead Sponsor | Collaborator |
---|---|
University of Edinburgh | Medical Research Council |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Safety in part A and part B and initial proof of concept in ICU to detect neutrophil activation. | Absence of any adverse events | Within 24 hours of delivery of NAP |
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