Release of Nociceptin From Granulocytes in Sepsis

NCT03037281 | Completed Results

• 1 other identifier: 0554
• Study Type: observational
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

Nociceptin is a protein found in the body, with a number of functions in the central nervous system, blood vessels and the gut. There is evidence that it may have a role in controlling the immune response to infection, and may act as a link between the brain and immune system. In infection, or after surgery, there is an increase in nociceptin, and subjects greater elevations of nociceptin have a poorer outcome. There is evidence that cells of the immune system may produce nociceptin, although it is not yet known which cells are capable of producing it, and what "switches on" production. This study aims to determine

1. 1.Which cells of the immune system can produce nociceptin
2. 2.If there is a difference in the ability to produce nociceptin between healthy volunteers and patients with severe infections

Conditions

Sepsis; Septic Shock; Sepsis Syndrome; Severe Sepsis

Outcome Measures

Primary Outcomes (1)

• Proportion of Responsive Biosensor Cells Responding to Granulocyte Addition in the Presence and Absence of NOP Antagonist

  Measure of N/OFQ presence in granulocytes and associated supernatant

  Day 1

Secondary Outcomes (6)

• Granulocyte Count

  Day 1

• Mortality In-hospital, at 30 Days

  30 days

• Time to ICU Discharge (or Death if on ICU)

  Time to ICU discharge (or death if on ICU)

• Time to Death or Discharge

  Number of days between admission and death or discharge from hospital

• Acute Physiology and Chronic Health Evaluation (APACHE-2) Score

  Day 1

Study Arms (2)

Septic

Patients admitted to the intensive care unit with a diagnosis of sepsis. For the purposes of this study, patients must have a diagnosis of sepsis; SIRS (2 of pulse \>90, WCC, BP, Oxygen(Dellinger et al., 2013)) with microbiological evidence of infection (positive blood culture, urine dipstick, compatible history or examination, radiographic evidence)

Diagnostic Test: Septic

Healthy volunteers

Healthy volunteers will be approached within the Department of Cardiovascular Sciences, and provided with the PIS, with consent taken by one of the investigating team.

Diagnostic Test: Septic

Interventions

Septic DIAGNOSTIC_TEST

30mls of blood will be sampled by venepuncture, or sampled from indwelling lines (in the case of septic patients on intensive care). Blood will be sampled using standard techniques, and transferred to EDTA containing blood bottles, and undergo processing immediately.

Also known as: Healthy volunteers

Healthy volunteers; Septic

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers - Adults, staff or students at the Univesity of Leicester, with no significant comorbidity Septic patients - Adult patients admitted to the adult intensive care unit, Leicester Royal Infirmary, with a diagnosis of sepsis

You may qualify if:

• For septic patients;
• Participant is willing and able to give informed consent for participation in the study, or if lacking capacity, a next of kin or advocate is willing and able to give assent for participation in the study. Must be able to read and understand English.
• Male or Female, aged 18 years or above.
• Diagnosed with sepsis and admitted to the intensive care unit.
• Able (in the Investigators opinion) and willing to comply with all study requirements.
• Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.
• Healthy Volunteers;
• Participant is willing and able to give informed consent for participation in the study. Must be able to read and understand English.
• Male or Female, aged 18 years or above and be
• In good health.
• Have had no course of medication, whether prescribed or over-the-counter, in the four weeks before first study dose and no individual doses in the final two weeks other than mild analgesia, vitamins and mineral supplements or, for females, oral contraceptives
• Able (in the Investigators opinion) and willing to comply with all study requirements.
• Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.

You may not qualify if:

• \. Conditions which may make phlebotomy hazardous to the participant (such as significant bleeding disorders or anaemia, or allergy), or to the investigator (blood viral infection).
• \. Any significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
• \. Participants who have participated in another research study involving an investigational product in the past 12 weeks.

Sponsors & Collaborators

• University of Leicester: lead
• The Royal College of Anaesthetists: collaborator
• University Hospitals, Leicester: collaborator

Study Sites (2)

Leicester Royal Infirmary

Leicester, Leicestershire, LE1 5WW, United Kingdom

Location

University of Leicester

Leicester, Leicestershire, LE2 7LX, United Kingdom

Location

MeSH Terms

Conditions

Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

Condition Hierarchy (Ancestors)

Infections; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Limitations and Caveats

Technical problems with both measurement and immunocyte extraction contributed to high variability with the assay and inconsistencies.Small numbers of subjects recruited precluded robust statistical analysis.Basophil extraction very low - not viable.

Results Point of Contact

• Title: Dr Christopher Hebbes
• Organization: University of Leicester

christopher.hebbes@le.ac.uk

0116 252 2522

Study Officials

• Christopher P Hebbes, BSc

  University of Leicester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2017
• First Posted: January 31, 2017
• Study Start: April 7, 2016
• Primary Completion: June 30, 2019
• Study Completion: June 30, 2019
• Last Updated: January 6, 2021
• Results First Posted: January 6, 2021

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)