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Clock Genes in Patients With Refractory Septic Shock (SeptiClock) - Pilot Study

Completed
Conditions
Septic Shock
Registration Number
NCT02044575
Lead Sponsor
Claudia Spies
Brief Summary

Despite large efforts trying to improve diagnostic and therapy of sepsis have been made over the last decade (e.g. initiation of the Surviving Sepsis Campaign, defining evidence based sepsis therapy bundles) the mortality of septic shock remains high and causes high socioeconomical burden of disease.

The purpose of this pilot study is to evaluate the design and conduct of a projected full scale clinical trial.

Detailed Description

A functional clock is required for induction of several proinflammatory genes, not shown in septic patient settings, yet.

Clock genes are involved in modulating the activity of several transcription factors that are important regulators of immune functions (e.g. HIF1-α, STAT1, STAT3, and NF-κB) (Bellet MM et al., 2013).

Furthermore, polymorphisms such as rs7221412, a common polymorphism near period homolog 1 (PER1), was associated with the timing of activity rhythms and also showed a suggestive time-dependent relationship with both cerebral cortex and monocytes PER1 expression and an association with time of death (Lim ASP et al., 2012).

This explorative project is a pilot study. First data are generated for the assessment of the circadian system in patients with septic shock.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
Inclusion Criteria
  • Male and female patients with age 18 years and above,
  • Patient at intensive care units (8i, 9i and 1i at Charité - University Medicine Berlin , Campus Virchow- Klinikum),
  • Septic shock (ACCP/SCCM (American College of Chest Physicians/Society of Critical Care Medicine) consensus definitions) AND Norepinephrine dosage of >0.3 μg/kg/min for at least 2 hours
Exclusion Criteria
  • Pregnant or lactating female patient,
  • Participation in another interventional study (30 days before study inclusion and during study participation),
  • Acute leucemia,
  • Severe leukocytosis (>50,000/nl),
  • Severe thrombocytopenia (<5,000/nl),
  • Autoimmune disease with systemic medication of ≥10 mg prednisolone equivalent or previous transplantation,
  • Patients receiving interferon therapy (last 14 days),
  • Patients with known hypersensitivity GM-CSF or known antibodies against GM-CSF, yeast-derived products or any component of the study medication,
  • Ongoing (concomitant) chemotherapy or radiotherapy for malignancy,
  • Acute pulmonary embolism or acute myocardial infarction within last 72 hours,
  • Cardiopulmonary resuscitation within last 7 days,
  • Moribund patient (life expectancy <72 hrs.),
  • Presence of a do-not-resuscitate or do-not-intubate order,
  • Known human immunodeficiency virus (HIV) infection or chronic viral hepatitis
  • Lacking willingness to save and hand out data within the study
  • Accommodation in an institution due to an official or judicial order
  • The informed consent of the patient or the subject's legally acceptable representative can´t be obtained in time
  • Patient has a power of attorney or patient's provision, where he/she refuses participation in any clinical trial

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Assessment of circadian regulationThese parameters are measured during intensive care unit stay, for a maximum of 3 days

Circadian regulation by expression of clock genes

Secondary Outcome Measures
NameTimeMethod
Light levels (lux)Light levels are measured until the end of intensive care unit stay - or, for a maximum of 28 days
CortisolThis parameter is measured in ng/ml during intensive care unit stay, for a maximum of 3 days
Sequential Organ Failure Assessment (SOFA)They are measured until the end of intensive care unit stay - or, for a maximum of 28 days.
Simplified Acute Physiology Score (SOFA II)They are measured until the end of intensive care unit stay - or, for a maximum of 28 days.
Therapeutic Intervention Scoring System (TISS-28)They are measured until the end of intensive care unit stay - or, for a maximum of 28 days.
Time on mechanical ventilationThey are followed up until the end of intensive care unit stay - or, for a maximum of 28 days
Hospital length of stayParticipants will be followed for the duration of intensive care stay, an expected average of 5 weeks
Intensive care unit length of stayParticipants will be followed for the duration of intensive care stay, an expected average of 4 weeks
MelatoninThis parameter is measured in pg/ml during intensive care unit stay, for a maximum of 3 days
Cognitive functionUp to 3 and 6 months

Cognitive function is measured by Repeatable Battery for the Assessment of Neuropsychological Status

Mortality6 months after intensive care unit discharge
Light frequenciesLight frequencies are measured until the end of intensive care unit stay - or, for a maximum of 28 days
Quality of lifeUp to 3 and 6 months

Quality of life is measured by SF-36 questionnaire

Multiplex-Genexpression analysisThese parameters are measured during intensive care unit stay, for a maximum of 3 days

Ncounter neuroinflammation and micro rna panel are analysed

Trial Locations

Locations (1)

Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow - Klinikum, Charité- Universitätsmedizin

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Berlin, Germany

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