Functionality of Endogenous Biological Clock in Sepsis

NCT04063332 | Unknown

• 1 other identifier: CLOCK
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of the current study is to demonstrate dysregulation of immune system΄s circadian rhythms as a consequence of sepsis, as well as marked malfunction of the central circadian clock in comparison with patients without sepsis , the presence of which burdens independently the final outcome and , hence, need to be addressed.

Conditions

Circadian Rhythm Disorders; Sepsis

Keywords

circadian; sepsis; clock; melatonin

Outcome Measures

Primary Outcomes (4)

• The substantial discrepancy in the values of melatonin, cortisol and core body temperature (central CLOCK circadian markers) between septic and non-septic patients.

  Different values in melatonin,cortisol, core body temperature .

  7 days

• The substantial discrepancy in the circadian rhythms' genes expression levels (peripheral clock markers) between septic and non-septic patients ,within their peripheral blood leucocytes .

  Different mRNA levels of clock, bmal1, per, cry genes within peripheral blood leucocytes.

  7 days

• The difference in the extent of deviation from normal, with regard to the values of melatonin-cortisol-core body temperature (circadian triad) between septic and non-septic patients.

  Extent of abnormality in the values of melatonin,cortisol and core body temperature .

  7 days

• The difference in the extent of deviation from normal, with regard to the levels of circadian rhythms' genes expression (immune system's clock) between septic and non-septic patients ,within their peripheral blood leucocytes .

  Extent of abnormality in the mRNA levels of clock, bmal1, per, cry genes within peripheral blood leucocytes.

  7 days

Secondary Outcomes (6)

• Mortality rate at 28 days.

  28 days

• Mortality rate at 90 days.

  90 days

• Munich ChronoType Questionnaire results ,including Mid-sleep, Sleep Duration on both work and free days (MSw, MSf, MSfsc, SLDw, SLDf, SLDØ, chronotype).

  30 days

• Pittsburgh Sleep Quality Index (Global PSQI Score).

  30 days

• Munich ChronoType Questionnaire results ,including Mid-sleep, Sleep Duration on both work and free days (MSw, MSf, MSfsc, SLDw, SLDf, SLDØ, chronotype).

  60 days

Study Arms (3)

GROUP A

Absolutely healthy individuals without any comorbidities, working at the same environment with the rest of groups (doctors are excluded as belong to one of the special categories) patients with sepsis as defined by the Sepsis-3 classification criteria3

GROUP B

Control patients without sepsis or infection and with the same exactly comorbidities (ideally ≤2 suffering organ systems) , i.e. identical Charlson score, identical mental status and age difference ≤ 5 years with group A

GROUP C

Patients with sepsis as defined by the Sepsis-3 classification criteria3

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

* GROUP A: absolutely healthy individuals without any comorbidities, working at the same environment with the rest of groups (doctors are excluded as belong to one of the special categories) patients with sepsis as defined by the Sepsis-3 classification criteria3 * GROUP Β: control patients without sepsis or infection and with the same exactly comorbidities (ideally ≤2 suffering organ systems) , i.e. identical Charlson score, identical mental status and age difference ≤ 5 years with group A * GROUP C: patients with sepsis as defined by the Sepsis-3 classification criteria3

You may qualify if:

• Adults (age ≥18 years)
• Written informed consent
• Male or female gender
• Οne of the following cases:
• Healthy controls without comorbidities OR
• Patients without sepsis or infection , with identical Charlson Comorbidity Index and same mental status with the septic patients OR
• Patients with sepsis

You may not qualify if:

• Failure to obtain written informed consent
• Age \<18 years
• Pregnancy or breastfeeding
• Solid tumor or hematologic malignancy
• Asthma
• Neurodegenerative disease
• Traumatic brain injury
• Confirmed depression
• Autoimmune disorders
• Special categories following unfixed or varying routine schedules (e.g. travels overseas or even short distances, if frequent/jet lag/on-call duties/nightshifts with regard to doctors,security guards,singers)
• Per os or iv corticosteroids daily intake of dose at least
• Corticosteroid oral or intravenous intake of at least 0.4 mg/kg of equivalent prednisone daily over the last 15 days

Sponsors & Collaborators

• University of Athens: lead
• Hellenic Sepsis Study Group: collaborator

Study Sites (2)

2nd Department of Intensive Care Medicine, Attikon University Hospital

Athens, Attica, 12462, Greece

RECRUITING

4th Department of Internal Medicine, Attikon University Hospital

Athens, Attica, 12462, Greece

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples for mRNA analysis and hormones' measurements

MeSH Terms

Conditions

Chronobiology Disorders; Sepsis

Condition Hierarchy (Ancestors)

Nervous System Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Evangelos J Giamarellos-Bourboulis, MD, PhD

  University of Athens

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Evangelos J Giamarellos-Bourboulis, MD, PhD

CONTACT

+302107480662; egiamarel@med.uoa.gr

Maria G Kalogridi, MD

CONTACT

+302105831916; mkalogr@med.uoa.gr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Professor of Internal Medicine ,President-Elect: European Shock Society, Co-ordinator: Hellenic Sepsis Study Group

Study Record Dates

• First Submitted: August 13, 2019
• First Posted: August 21, 2019
• Study Start: June 3, 2019
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: December 12, 2023

Record last verified: 2023-12

Locations

GR (2)