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Trial record 51 of 657 for:    Recruiting, Not yet recruiting, Available Studies | "Muscular Diseases"

Impact of Human Blood Serum From Critically Ill Patients on Human Colon Neuronal Networks.

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ClinicalTrials.gov Identifier: NCT02706314
Recruitment Status : Recruiting
First Posted : March 11, 2016
Last Update Posted : October 25, 2017
Sponsor:
Information provided by (Responsible Party):
Dr. Johannes Ehler, MD, University of Rostock

Brief 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. 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:

  1. 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
  2. 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)

Condition or disease
Critical Illness Multiple Organ Failure Polyneuropathy Myopathy

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 Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Case-Control
Time Perspective: Prospective
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
Study Start Date : March 2016
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : December 2018

Group/Cohort
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



Primary Outcome Measures :
  1. 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).

  2. 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).


Secondary Outcome Measures :
  1. Incidence of CIP assessed by standardized nerve conduction study [ Time Frame: Day 10 ]
    CIP defined as a reduction in the amplitude of compound muscle action potentials and sensory nerve action potentials

  2. Incidence of CIP assessed by standardized neurological examination [ Time Frame: Day 10 ]
    CIP defined as decreased or absent tendon reflexes and/or muscular paresis

  3. Incidence of peripheral nerve abnormalities assessed by neuromyosonography [ Time Frame: Day 10 ]
    Defined as increased nerve cross sectional areas in mm²

  4. Incidence of abnormalities of muscle echogenicity assesed by neuromyosonography [ Time Frame: Day 10 ]
    Abnormal muscle echogenicity defined as mild, moderate or massive increased echogenicity in comparison to bone echogenicity

  5. Time of respirator-therapy [ Time Frame: Day 100 ]
  6. Length of ICU stay [ Time Frame: Day 100 ]
  7. The number of participants with death [ Time Frame: Day 100 ]

Biospecimen Retention:   Samples Without DNA
Serum probes will be stored at -80°C.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
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.
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Diagnosis of pre-existing neuromuscular diseases other than CIP
  • High-dose glucocorticosteroid therapy (> 300 mg Hydrocortisone/die)
  • Age < 18

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02706314


Contacts
Contact: Johannes Ehler, MD +493814946401 johannes.ehler@med.uni-rostock.de
Contact: Robert Patejdl, MD +493814948006 robert.patejdl@uni-rostock.de

Locations
Germany
Intensive Care Unit PIT 1 and 2, University hospital Rostock Recruiting
Rostock, Germany, 18055
Contact: Johannes Ehler, MD    +493814946401    johannes.ehler@med.uni-rostock.de   
Sponsors and Collaborators
University of Rostock

Responsible Party: Dr. Johannes Ehler, MD, Dr. med. Johannes Ehler, University of Rostock
ClinicalTrials.gov Identifier: NCT02706314     History of Changes
Other Study ID Numbers: A 2016-0016
First Posted: March 11, 2016    Key Record Dates
Last Update Posted: October 25, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Critical Illness
Polyneuropathies
Multiple Organ Failure
Disease Attributes
Pathologic Processes
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Shock