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

Septic Shock Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02044575
• Other study ID #: SeptiClock
• Status: Completed
• Start date: April 2014
• Est. completion date: March 31, 2019

Study information

• Verified date: June 2020
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 31, 2019
• Est. primary completion date: January 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Locations

Country	Name	City	State
Germany	Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow - Klinikum, Charité- Universitätsmedizin	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Claudia Spies

Country where clinical trial is conducted

Germany, 

References & Publications (2)

Bellet MM, Deriu E, Liu JZ, Grimaldi B, Blaschitz C, Zeller M, Edwards RA, Sahar S, Dandekar S, Baldi P, George MD, Raffatellu M, Sassone-Corsi P. Circadian clock regulates the host response to Salmonella. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9897-902. doi: 10.1073/pnas.1120636110. Epub 2013 May 28. — View Citation

Lim AS, Chang AM, Shulman JM, Raj T, Chibnik LB, Cain SW, Rothamel K, Benoist C, Myers AJ, Czeisler CA, Buchman AS, Bennett DA, Duffy JF, Saper CB, De Jager PL. A common polymorphism near PER1 and the timing of human behavioral rhythms. Ann Neurol. 2012 Sep;72(3):324-34. doi: 10.1002/ana.23636. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Nagalase enzyme activity	Nagalase Enzyme activity is expressed in nmol/min per Milliliter. Analysis is evaluated with the perioperative Nagalase results of 10 patients in the clinical trial Phydelio (EudraCT-No 2008-007237-47).	This parameter is measured at the beginning of the investigation
Other	Venous return	Venous return will be assessed after ICU admission by venous return pressure gradient (dVR)	This parameter is measured at the beginning of the investigation
Primary	Assessment of circadian regulation	Circadian regulation by expression of clock genes	These parameters are measured during intensive care unit stay, for a maximum of 3 days
Secondary	Time on mechanical ventilation		They are followed up until the end of intensive care unit stay - or, for a maximum of 28 days
Secondary	Intensive care unit length of stay		Participants will be followed for the duration of intensive care stay, an expected average of 4 weeks
Secondary	Hospital length of stay		Participants will be followed for the duration of intensive care stay, an expected average of 5 weeks
Secondary	Simplified Acute Physiology Score (SOFA II)		They are measured until the end of intensive care unit stay - or, for a maximum of 28 days.
Secondary	Sequential Organ Failure Assessment (SOFA)		They are measured until the end of intensive care unit stay - or, for a maximum of 28 days.
Secondary	Therapeutic Intervention Scoring System (TISS-28)		They are measured until the end of intensive care unit stay - or, for a maximum of 28 days.
Secondary	Mortality		6 months after intensive care unit discharge
Secondary	Light frequencies		Light frequencies are measured until the end of intensive care unit stay - or, for a maximum of 28 days
Secondary	Light levels (lux)		Light levels are measured until the end of intensive care unit stay - or, for a maximum of 28 days
Secondary	Cortisol		This parameter is measured in ng/ml during intensive care unit stay, for a maximum of 3 days
Secondary	Melatonin		This parameter is measured in pg/ml during intensive care unit stay, for a maximum of 3 days
Secondary	Quality of life	Quality of life is measured by SF-36 questionnaire	Up to 3 and 6 months
Secondary	Cognitive function	Cognitive function is measured by Repeatable Battery for the Assessment of Neuropsychological Status	Up to 3 and 6 months
Secondary	Multiplex-Genexpression analysis	Ncounter neuroinflammation and micro rna panel are analysed	These parameters are measured during intensive care unit stay, for a maximum of 3 days