Release of Nociceptin From Granulocytes in Sepsis

Does the Release Profile of Nociceptin From Immunocytes Differ in Healthy Volunteers and Critically Ill Patients With Sepsis?

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

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock; Severe Sepsis; Sepsis Syndrome
• Intervention / Treatment: Diagnostic test: Septic

• Study Type: Observational
• Enrollment (Actual): 14

Contacts and Locations

Study Locations

• United Kingdom
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary
    • Leicester, Leicestershire, United Kingdom, LE2 7LX
      • University of Leicester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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

Description

Inclusion Criteria:

• For septic patients;

  1. 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.
  2. Male or Female, aged 18 years or above.
  3. Diagnosed with sepsis and admitted to the intensive care unit.
  4. Able (in the Investigators opinion) and willing to comply with all study requirements.
  5. Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.

Healthy Volunteers;

1. Participant is willing and able to give informed consent for participation in the study. Must be able to read and understand English.
2. Male or Female, aged 18 years or above and be
3. In good health.
4. 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
5. Able (in the Investigators opinion) and willing to comply with all study requirements.
6. Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.

Exclusion Criteria:

• 1. 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).

  2. 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.

  3. Participants who have participated in another research study involving an investigational product in the past 12 weeks.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; 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.; Other Names: Healthy volunteers
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; 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.; Other Names: Healthy volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Granulocyte Count	Count of the number of neutrophils in the original sample	Day 1
Mortality In-hospital, at 30 Days	All cause mortality 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	Time to death or discharge (days)	Number of days between admission and death or discharge from hospital
Acute Physiology and Chronic Health Evaluation (APACHE-2) Score	The Acute Physiology and Chronic Health Evaluation (APACHE-2) score for the patient. APACHE 2 is an international standard,12 variable score from 0-71 reflecting disease severity in the critically unwell during the first 24 hours of illness. The score is a combined measure of illness severity (acute physiology), and background chronic health factors. Increased score represents increased predicted mortality. Variables recorded include AaDO2 or PaO2 (depending on FiO2), temperature, mean arterial pressure, blood pH, heart rate, respiratory rate, serum sodium, serum potassium, creatinine, hematocrit, white blood cell count, Glasgow Coma Scale Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985). "APACHE II: a severity of disease classification system". Critical Care Medicine. 13 (10): 818-29	Day 1
Sequential Organ Failure Assessment (SOFA) Score	The Sequential Organ Failure Assessment (SOFA) score for the patient, a score predictive of mortality in sepsis for intensive care patients based on respiratory, cardiovascular, hepatic, coagulation, renal and neurological function (each scored 0-4, with a maximum overall score of 24). The worst (most deranged) physiological values for the first 24 hours are used. A higher score predicts increased mortality. The mortality breakdown for each sofa score range is - SOFA 0-6 (<10% mortality), 7-9 (15-20%), 10-12 (40-50%), 13-14 (50 - 60%), 15 (> 80%), 16 to 24 (> 90%)	Day 1

Collaborators and Investigators

• Sponsor: University of Leicester
• Collaborators: University Hospitals, Leicester; The Royal College of Anaesthetists
• Investigators: Principal Investigator: Christopher P Hebbes, BSc, University of Leicester

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 7, 2016
• Primary Completion (ACTUAL): June 30, 2019
• Study Completion (ACTUAL): June 30, 2019

Study Registration Dates

• First Submitted: January 25, 2017
• First Submitted That Met QC Criteria: January 30, 2017
• First Posted (ESTIMATE): January 31, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 6, 2021
• Last Update Submitted That Met QC Criteria: December 10, 2020
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Shock; Sepsis; Toxemia; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: 0554

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No