Septic ShockNCT02044575
Clock Genes in Patients With Refractory Septic Shock (SeptiClock) - Pilot Study
An observational study of Septic Shock, run by Claudia Spies at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2014to 31 Mar 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Critically ill patients with septic shock
Who may be able to join
- 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
Who cannot join
- 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,
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow - Klinikum, Charité- Universitätsmedizin
Berlin, 13353
About this study
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.
Read the 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.
- Conditions
- Septic Shock
- Keywords
- Clock genes, circadian regulation
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Critically ill patients | Intensive care unit patients with refractory septic shock |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of circadian regulation
Circadian regulation by expression of clock genes
Measured: These parameters are measured during intensive care unit stay, for a maximum of 3 days
Secondary outcomes (14)
Time on mechanical ventilation
Measured: They are followed up until the end of intensive care unit stay - or, for a maximum of 28 days
Intensive care unit length of stay
Measured: Participants will be followed for the duration of intensive care stay, an expected average of 4 weeks
Hospital length of stay
Measured: Participants will be followed for the duration of intensive care stay, an expected average of 5 weeks
Simplified Acute Physiology Score (SOFA II)
Measured: They are measured until the end of intensive care unit stay - or, for a maximum of 28 days.
Sequential Organ Failure Assessment (SOFA)
Measured: They are measured until the end of intensive care unit stay - or, for a maximum of 28 days.
Therapeutic Intervention Scoring System (TISS-28)
Measured: They are measured until the end of intensive care unit stay - or, for a maximum of 28 days.
Mortality
Measured: 6 months after intensive care unit discharge
Light frequencies
Measured: Light frequencies are measured until the end of intensive care unit stay - or, for a maximum of 28 days
Light levels (lux)
Measured: Light levels are measured until the end of intensive care unit stay - or, for a maximum of 28 days
Cortisol
Measured: This parameter is measured in ng/ml during intensive care unit stay, for a maximum of 3 days
Melatonin
Measured: This parameter is measured in pg/ml during intensive care unit stay, for a maximum of 3 days
Quality of life
Quality of life is measured by SF-36 questionnaire
Measured: Up to 3 and 6 months
Cognitive function
Cognitive function is measured by Repeatable Battery for the Assessment of Neuropsychological Status
Measured: Up to 3 and 6 months
Multiplex-Genexpression analysis
Ncounter neuroinflammation and micro rna panel are analysed
Measured: These parameters are measured during intensive care unit stay, for a maximum of 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2014 (estimated)
- Study startApr 2014
- Primary completion21 Jan 2018
- Study completion31 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Claudia Spies
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Claudia Spies, Charite University, Berlin, Germany
- Investigators
- Claudia Spies, MD, Prof., Study director, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02044575
- Sponsor's protocol ID
- SeptiClock
- Status last verified
- Jun 2020
- First submitted
- 20 Jan 2014
- Last updated
- 16 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23716692Lim 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.
PubMed 23034908Lachmann G, Ananthasubramaniam B, Wunsch VA, Scherfig LM, von Haefen C, Knaak C, Edel A, Ehlen L, Koller B, Goldmann A, Herzel H, Kramer A, Spies C. Circadian rhythms in septic shock patients. Ann Intensive Care. 2021 Apr 26;11(1):64. doi: 10.1186/s13613-021-00833-5.
PubMed 33900485
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clock Genes in Patients With Refractory Septic Shock (SeptiClock) - Pilot Study
- ClinicalTrials.gov ID
- NCT02044575
- Acronym / sponsor ID
- SeptiClock
- Conditions
- Septic Shock
- Keywords
- Clock genes, circadian regulation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Claudia SpiesUniversity, hospital or other
- Study start
- Apr 2014 (actual)
- Primary completion
- 21 Jan 2018 (actual)
- Study completion
- 31 Mar 2019 (actual)
- First posted
- 24 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Critically ill patients | – | –Intensive care unit patients with refractory septic shock |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Critically ill patients with septic shock
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (18 listed)
- 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),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Assessment of circadian regulation
Time frame: These parameters are measured during intensive care unit stay, for a maximum of 3 days
Circadian regulation by expression of clock genes
14 secondary outcomes
Time on mechanical ventilation
Time frame: They are followed up until the end of intensive care unit stay - or, for a maximum of 28 days
Intensive care unit length of stay
Time frame: Participants will be followed for the duration of intensive care stay, an expected average of 4 weeks
Hospital length of stay
Time frame: Participants will be followed for the duration of intensive care stay, an expected average of 5 weeks
Simplified Acute Physiology Score (SOFA II)
Time frame: They are measured until the end of intensive care unit stay - or, for a maximum of 28 days.
Sequential Organ Failure Assessment (SOFA)
Time frame: They are measured until the end of intensive care unit stay - or, for a maximum of 28 days.
Therapeutic Intervention Scoring System (TISS-28)
Time frame: They are measured until the end of intensive care unit stay - or, for a maximum of 28 days.
Mortality
Time frame: 6 months after intensive care unit discharge
Light frequencies
Time frame: Light frequencies are measured until the end of intensive care unit stay - or, for a maximum of 28 days
Light levels (lux)
Time frame: Light levels are measured until the end of intensive care unit stay - or, for a maximum of 28 days
Cortisol
Time frame: This parameter is measured in ng/ml during intensive care unit stay, for a maximum of 3 days
Melatonin
Time frame: This parameter is measured in pg/ml during intensive care unit stay, for a maximum of 3 days
Quality of life
Time frame: Up to 3 and 6 months
Cognitive function
Time frame: Up to 3 and 6 months
Multiplex-Genexpression analysis
Time frame: These parameters are measured during intensive care unit stay, for a maximum of 3 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2020.
- Background: PubMed 23716692Bellet 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.
- Background: PubMed 23034908Lim 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.
- Derived from this study: PubMed 33900485Lachmann G, Ananthasubramaniam B, Wunsch VA, Scherfig LM, von Haefen C, Knaak C, Edel A, Ehlen L, Koller B, Goldmann A, Herzel H, Kramer A, Spies C. Circadian rhythms in septic shock patients. Ann Intensive Care. 2021 Apr 26;11(1):64. doi: 10.1186/s13613-021-00833-5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claudia Spies, MD, Prof. study director
Charite University, Berlin, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Septic Shock, run by Claudia Spies at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of circadian regulation (time frame: These parameters are measured during intensive care unit stay, for a maximum of 3 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02044575, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2020.