Critical IllnessNCT02706314
Impact of Human Blood Serum From Critically Ill Patients on Human Colon Neuronal Networks.
An observational study of Critical Illness and Multiple Organ Failure, run by University of Rostock at 1 site in Germany.
Trial summary
Critical illness in the ICU setting has high medical and socioeconomic importance. Critically ill patients frequently develop severe neurologic impairment during their course of disease, typically presenting as critical-illness-polyneuropathy (CIP), which is associated with an increased mortality rate. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Critical Illness, Multiple Organ Failure, Polyneuropathy
- How many people
- 61 participants
- Where
- 1 siteGermany
- Study dates
- Mar 2016to 16 Apr 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: All patients with critical illness and fulfilling the inclusion criteria should be screened for the study on two surgical ICUs at the university hospital of Rostock, Germany.
Who may be able to join
- Patients with critical illness, defined as a SOFA-Score ≥ 8 on 3 consecutive days within the first 5 days of ICU stay
- Informed consent by patient or legal proxy
Who cannot join
- Diagnosis of pre-existing neuromuscular diseases other than CIP
- High-dose glucocorticosteroid therapy (> 300 mg Hydrocortisone/die)
- Age < 18
Trial locations and contacts
1 site in 1 country.
Germany1 site
Intensive Care Unit PIT 1 and 2, University hospital Rostock
Rostock, 18055
About this study
Official title: Pilot Observation of the Impact of Human Blood Serum From Critically Ill Patients With or Without Critical-illness-polyneuropathy on Intramural Neuronal Networks of Human Colon Samples
Critical illness in the ICU setting has high medical and socioeconomic importance. Critically ill patients frequently develop severe neurologic impairment during their course of disease, typically presenting as critical-illness-polyneuropathy (CIP), which is associated with an increased mortality rate. To date neither strategies are available to predict nor to specifically treat CIP.
Diagnostic tests to determine CIP during the course of critical illness are available through nerve conduction studies. Further research is needed to find diagnostic tools to identify patients who are on high risk to develop CIP, which could encourage the evolution of new therapeutic strategies for CIP patients.
Read more
The aims of the study are:
- An early detection of changes in intramural neuronal networks of human colon samples induced by human blood serum from critically ill patients in order to predict the development of CIP
- The comparison of different diagnostic tests to diagnose and monitor CIP during the course of critical illness (neurologic examination versus nerve conduction study versus neuromyosonography)
Read the detailed description
All patients with critical illness and fulfilling the inclusion criteria should be screened for the study on two surgical ICUs at the university hospital of Rostock, Germany.
The inclusion of patients will be started if written informed consent was obtained from all participants or their representatives (if direct consent could not be obtained).
The aim of the study is a prediction or an earlier detection of CIP in critically ill patients before nerve conduction studies are able to diagnose CIP. We hypothesize that upregulated circulating neurotoxic factors in human serum of critically ill patients cause neuronal damage and play an important role in the pathogenesis of CIP. Time from upregulation of neurotoxic factors to the clinical appearance of neuronal damage (CIP) is unknown.
An experimental part of the study aims at establishing enteric neuronal networks as functional bioassays for the qualitative detection of neurotoxic humoral factors. Human colon samples will be exposed to the serum of critically ill patients with and without CIP in an organ bath (100% serum) under standardized physiologic conditions. Alterations to neuronal functions (contractions, spontaneous activity) will be studied between serum from patients with CIP, without CIP and serum probes from healthy volunteers (without critical illness).
In a clinical part of the study critically ill patients with and without CIP (detected by nerve conduction studies as the gold standard for the diagnosis of CIP) will be examined by neurologic examination, nerve conduction study and neuromyosonography of peripheral nerves. The incidence, the extent and the time from the beginning of critical illness to the clinical appearance of nerval alterations will be compared between the 3 diagnostic tests.
From all patients basic demographic data, illness severity scores (APACHE-II, SOFA) laboratory results, pre-morbidity data and clinical outcome for the study cohort will be recorded. At day 3 and 10 patients will be examined by neurologic examination, nerve conduction study, neuromyosonography and laboratory tests (inflammation, coagulation, organ function, blood parameters including TNF-alpha, IL-6, S100b, oxidative stress markers, neurofilaments, C-type natriuretic peptide).
- Conditions
- Critical Illness, Multiple Organ Failure, Polyneuropathy, Myopathy
- Medical subject headings
- Critical Illness, Multiple Organ Failure, Polyneuropathies, Muscular Diseases
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 with CIP | Critically ill patients with a Sequential Organ Failure Assessment (SOFA)-Score >7 with CIP | |
| Critically ill patients without CIP | Critically ill patients with a Sequential Organ Failure Assessment (SOFA)-Score >7 without CIP | |
| Healthy volunteers | Healthy volunteers with neither critical illness nor CIP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in the frequency and the amplitude of spontaneous contractions of colonic smooth muscle preparations induced by incubation with serum from critically ill patients with CIP, without CIP and healthy controls
The parameters will be measured in colonic smooth muscle preparations before and after three hours of incubation with serum from healthy controls as well as critically ill patients with or without CIP. The observed changes in the respective parameter over the three-hour period will be estimated in each tested preparation as measured by absolute values of frequency (contractions per minute) and force (millinewton).
Measured: Baseline and 3 Hours
Changes in the amplitude, the integrated force and the time to first and last peak of contractions evoked by electric field stimulation in colonic smooth muscle preparations incubated with the above mentioned sera
Applying the same time protocol as described above for point 1, except for the use of electric field stimulation as an exogenous trigger of contractions, changes in the respective parameter over the three-hour period will be estimated in each tested preparation as measured by absolute values of force (millinewton), integrated force (millinewton*second) and time (seconds).
Measured: Baseline and 3 Hours
Secondary outcomes (7)
Incidence of CIP assessed by standardized nerve conduction study
CIP defined as a reduction in the amplitude of compound muscle action potentials and sensory nerve action potentials
Measured: Day 10
Incidence of CIP assessed by standardized neurological examination
CIP defined as decreased or absent tendon reflexes and/or muscular paresis
Measured: Day 10
Incidence of peripheral nerve abnormalities assessed by neuromyosonography
Defined as increased nerve cross sectional areas in mm²
Measured: Day 10
Incidence of abnormalities of muscle echogenicity assesed by neuromyosonography
Abnormal muscle echogenicity defined as mild, moderate or massive increased echogenicity in comparison to bone echogenicity
Measured: Day 10
Time of respirator-therapy
Measured: Day 100
Length of ICU stay
Measured: Day 100
The number of participants with death
Measured: Day 100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2016 (estimated)
- Study startMar 2016
- Primary completion16 Apr 2019
- Study completion16 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rostock
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Johannes Ehler, MD, University of Rostock
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02706314
- Sponsor's protocol ID
- A 2016-0016
- Status last verified
- Apr 2019
- First submitted
- 23 Feb 2016
- Last updated
- 18 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Klawitter F, Laukien F, Fischer DC, Rahn A, Porath K, Danckert L, Bajorat R, Walter U, Patejdl R, Ehler J. Longitudinal Assessment of Blood-Based Inflammatory, Neuromuscular, and Neurovascular Biomarker Profiles in Intensive Care Unit-Acquired Weakness: A Prospective Single-Center Cohort Study. Neurocrit Care. 2025 Feb;42(1):118-130. doi: 10.1007/s12028-024-02050-x. Epub 2024 Jul 9.
PubMed 38982001
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Observation of the Impact of Human Blood Serum From Critically Ill Patients With or Without Critical-illness-polyneuropathy on Intramural Neuronal Networks of Human Colon Samples
- ClinicalTrials.gov ID
- NCT02706314
- Acronym / sponsor ID
- A 2016-0016
- Conditions
- Critical Illness, Multiple Organ Failure, Polyneuropathy, Myopathy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- University of RostockUniversity, hospital or other
- Study start
- Mar 2016
- Primary completion
- 16 Apr 2019 (actual)
- Study completion
- 16 Apr 2019 (actual)
- First posted
- 11 Mar 2016 (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.
Critical illness in the ICU setting has high medical and socioeconomic importance. Critically ill patients frequently develop severe neurologic impairment during their course of disease, typically presenting as critical-illness-polyneuropathy (CIP), which is associated with an increased mortality rate. To date neither strategies are available to predict nor to specifically treat CIP.
Diagnostic tests to determine CIP during the course of critical illness are available through nerve conduction studies. Further research is needed to find diagnostic tools to identify patients who are on high risk to develop CIP, which could encourage the evolution of new therapeutic strategies for CIP patients.
The aims of the study are:
- An early detection of changes in intramural neuronal networks of human colon samples induced by human blood serum from critically ill patients in order to predict the development of CIP
- The comparison of different diagnostic tests to diagnose and monitor CIP during the course of critical illness (neurologic examination versus nerve conduction study versus neuromyosonography)
Detailed description
All patients with critical illness and fulfilling the inclusion criteria should be screened for the study on two surgical ICUs at the university hospital of Rostock, Germany.
The inclusion of patients will be started if written informed consent was obtained from all participants or their representatives (if direct consent could not be obtained).
The aim of the study is a prediction or an earlier detection of CIP in critically ill patients before nerve conduction studies are able to diagnose CIP. We hypothesize that upregulated circulating neurotoxic factors in human serum of critically ill patients cause neuronal damage and play an important role in the pathogenesis of CIP. Time from upregulation of neurotoxic factors to the clinical appearance of neuronal damage (CIP) is unknown.
An experimental part of the study aims at establishing enteric neuronal networks as functional bioassays for the qualitative detection of neurotoxic humoral factors. Human colon samples will be exposed to the serum of critically ill patients with and without CIP in an organ bath (100% serum) under standardized physiologic conditions. Alterations to neuronal functions (contractions, spontaneous activity) will be studied between serum from patients with CIP, without CIP and serum probes from healthy volunteers (without critical illness).
In a clinical part of the study critically ill patients with and without CIP (detected by nerve conduction studies as the gold standard for the diagnosis of CIP) will be examined by neurologic examination, nerve conduction study and neuromyosonography of peripheral nerves. The incidence, the extent and the time from the beginning of critical illness to the clinical appearance of nerval alterations will be compared between the 3 diagnostic tests.
From all patients basic demographic data, illness severity scores (APACHE-II, SOFA) laboratory results, pre-morbidity data and clinical outcome for the study cohort will be recorded. At day 3 and 10 patients will be examined by neurologic examination, nerve conduction study, neuromyosonography and laboratory tests (inflammation, coagulation, organ function, blood parameters including TNF-alpha, IL-6, S100b, oxidative stress markers, neurofilaments, C-type natriuretic peptide).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Critically ill patients with CIP | – | –Critically ill patients with a Sequential Organ Failure Assessment (SOFA)-Score >7 with CIP |
| Critically ill patients without CIP | – | –Critically ill patients with a Sequential Organ Failure Assessment (SOFA)-Score >7 without CIP |
| Healthy volunteers | – | –Healthy volunteers with neither critical illness nor CIP |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- All patients with critical illness and fulfilling the inclusion criteria should be screened for the study on two surgical ICUs at the university hospital of Rostock, Germany.
Key inclusion criteria (2 listed)
- Patients with critical illness, defined as a SOFA-Score ≥ 8 on 3 consecutive days within the first 5 days of ICU stay
- Informed consent by patient or legal proxy
Key exclusion criteria (3 listed)
- Diagnosis of pre-existing neuromuscular diseases other than CIP
- High-dose glucocorticosteroid therapy (> 300 mg Hydrocortisone/die)
- Age < 18
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
Changes in the frequency and the amplitude of spontaneous contractions of colonic smooth muscle preparations induced by incubation with serum from critically ill patients with CIP, without CIP and healthy controls
Time frame: Baseline and 3 Hours
The parameters will be measured in colonic smooth muscle preparations before and after three hours of incubation with serum from healthy controls as well as critically ill patients with or without CIP. The observed changes in the respective parameter over the three-hour period will be estimated in each tested preparation as measured by absolute values of frequency (contractions per minute) and force (millinewton).
Changes in the amplitude, the integrated force and the time to first and last peak of contractions evoked by electric field stimulation in colonic smooth muscle preparations incubated with the above mentioned sera
Time frame: Baseline and 3 Hours
Applying the same time protocol as described above for point 1, except for the use of electric field stimulation as an exogenous trigger of contractions, changes in the respective parameter over the three-hour period will be estimated in each tested preparation as measured by absolute values of force (millinewton), integrated force (millinewton*second) and time (seconds).
7 secondary outcomes
Incidence of CIP assessed by standardized nerve conduction study
Time frame: Day 10
Incidence of CIP assessed by standardized neurological examination
Time frame: Day 10
Incidence of peripheral nerve abnormalities assessed by neuromyosonography
Time frame: Day 10
Incidence of abnormalities of muscle echogenicity assesed by neuromyosonography
Time frame: Day 10
Time of respirator-therapy
Time frame: Day 100
Length of ICU stay
Time frame: Day 100
The number of participants with death
Time frame: Day 100
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 18 Apr 2019.
- Derived from this study: PubMed 38982001Klawitter F, Laukien F, Fischer DC, Rahn A, Porath K, Danckert L, Bajorat R, Walter U, Patejdl R, Ehler J. Longitudinal Assessment of Blood-Based Inflammatory, Neuromuscular, and Neurovascular Biomarker Profiles in Intensive Care Unit-Acquired Weakness: A Prospective Single-Center Cohort Study. Neurocrit Care. 2025 Feb;42(1):118-130. doi: 10.1007/s12028-024-02050-x. Epub 2024 Jul 9.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Critical Illness and Multiple Organ Failure, run by University of Rostock 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 2 inclusion and 3 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 18 Apr 2019. 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?
Changes in the frequency and the amplitude of spontaneous contractions of colonic smooth muscle preparations induced by incubation with serum from critically ill patients with CIP, without CIP and healthy controls (time frame: Baseline and 3 Hours). The study lists 2 primary outcomes in all. 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 NCT02706314, which also lists 1 linked publication.
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 18 Apr 2019.