Liver CirrhosesNCT04131205
Role of MRI in Detection of Minimal Hepatic Encephalopathy
An observational study of Liver Cirrhoses and Hepatic Encephalopathy, run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial summary
Introduction Liver cirrhosis (LC) is irreversible fibrosis of the liver (1) and it remains a public health problem. One of the complications of the cirrhosis is hepatic encephalopathy (HE) which is defined as brain dysfunction caused by liver insufficiency. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Liver Cirrhoses, Hepatic Encephalopathy
- What is being tested?
- Magnetic Resonance Imaging
- How many people
- 40 participants
- Where
- 1 siteSlovenia
- Study dates
- 1 Jun 2019to 1 Jun 2023
- 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 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: We will include 10-20 patients of both genders with signs of hepatic encephalopathy and 10-20 patients of both genders without HE. Diagnosis of HE will be made based on results of validated neuropsychiatric test. Age-matched and gender-matched control group with no gastrointestinal, neurological or psychiatric complaints and normal levels of ammonia in the blood.
Who may be able to join
- Known liver disease/cirrhosis
Who cannot join
- Pregnancy, non compatible material with MRI
Trial locations and contacts
1 site in 1 country.
Sebastian Stefanovic, M.D. contact
Slovenia1 site, 1 recruiting
- Recruiting
Department of Gastroenterology and Hepatology, University Medical Centre Ljubljana
Ljubljana, 1000
Sebastian Stefanovic, M.D., 0038615224166, sebastian.stefanovic@gmail.com
Marjana Turk Jerovsek, M.D., 0038615224166, marjanca88@gmail.com
About this study
Official title: Role of Magnetic Resonance Imaging in Detection of Minimal Hepatic Encephalopathy
Introduction Liver cirrhosis (LC) is irreversible fibrosis of the liver (1) and it remains a public health problem. One of the complications of the cirrhosis is hepatic encephalopathy (HE) which is defined as brain dysfunction caused by liver insufficiency. Pathophysiological mechanisms of HE are complex and multifactorial. Recognition of beginning stages of HE, such as minimal HE (mHE) is of most importance.
Objectives and originality of the project Diagnosis of mHE can be challenging, time-consuming and, at least to some extent, subjective. This project will assess the role of magnetic resonance (MR) in mHE diagnosis with emphasis on multimodal imaging technique. With advanced magnetic resonance (MR) techniques, in-vivo detection of intracellular water content, estimation pH and metabolites levels with millimolar concentrations can be easily performed. This will offer to explore possible pathophysiological mechanisms of HE and to evaluate the results from previous, studies that were mainly performed on animal models or cell cultures.
Read more
By our best knowledge, multimodal MR approach as the investigators propose in this application has not been yet performed. The investigators will use advanced MR techniques which are currently not available in the clinical setting and require multicenter collaboration.
Methods The investigators will include 10-20 patients of both genders with hyperammonemia and mHE and 10-20 patients of both genders with HE. Diagnosis of HE will be made based on results of validated neuropsychiatric test. Age-matched and gender-matched control group with no gastrointestinal, neurological or psychiatric complaints and normal levels of ammonia in the blood. Patients with mHE/HE will be included from outpatient clinic of the Department of gastroenterology, University Medical Centre (UMC) Ljubljana. Healthy controls (HC) will be invited to join via internet advertisement. Contraindications for HC will include gastrointestinal (emphasis on liver disease), neurological or psychiatric complaints. Grade of mHE/HE will be classified according to West-Haven (WH) classification. Patients with different degree of liver cirrhosis, which will be scored with the Child-Pugh (CP) score, and with no contraindications for MR (e.g. presence of metal in body) will be included. Blood levels of liver enzymes and ammonia will be measured in all participants. MR scanning will include: T1- and T2-weighted MR, MRS (MEGA-PRESS and PRESS) in two voxels: striatum and cerebellum. Location will be double-checked by voxel position screenshots. Analysis, with voxel-positioning error compensation will be performed in Gannet (www.gabamrs.com). Moreover, high resolution diffusion weighted imaging (DWI), diffusion kurtosis imaging (DKI), quantitative susceptibility mapping (QSM) will be performed in brain as well. Liver QSM will be executed to assess iron load.
- Conditions
- Liver Cirrhoses, Hepatic Encephalopathy
- Being tested
- Magnetic Resonance Imaging
- Medical subject headings
- Hepatic Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance ImagingDiagnostic test
Also called Ammonia Levels, Child Pugh Score, West-Haven grade of Hepatic Encephalopathy
We will assess the role of magnetic resonance (MR) in mHE diagnosis with emphasis on multimodal imaging technique
| Study group | Role | What they receive |
|---|---|---|
| Minimal Hepatic Encephalopathy | Patients with hyperammonemia and minimal hepatic encephalopathy Receives: Diagnostic Test: Magnetic Resonance Imaging | |
| Control | Healthy controls Receives: Diagnostic Test: Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Structural and Functional Changes in Brain Structures with Magnetic Resonance Imaging
GABA levels and other neurotransmitters with respect to the tissue water signal and corrected for tissue composition.
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2019
- Study start1 Jun 2019
- Primary completion1 Jun 2023 (estimated)
- Study completion1 Jun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (30)Papers the sponsor has linked to this study.
- Other trials for Liver CirrhosesStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe sponsor's other registered studies.
- 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
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Collaborators
- University of Ljubljana, Faculty of Medicine, Medical University of Graz, Johns Hopkins University
- Responsible party
- Principal investigator, Sebastian Stefanovic, MD, University Medical Centre Ljubljana
- Investigators
- Dusan Suput, M.D., Study chair, Medical Faculty of LjubljanaBorut Stabuc, M.D., Study chair, Department of Gastroenterology and Hepatology, University Medical Centre Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04131205
- Sponsor's protocol ID
- HepaticEncephalopathy
- Status last verified
- Oct 2019
- First submitted
- 15 Oct 2019
- Last updated
- 18 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
American Association for the Study of Liver Diseases; European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014 Sep;61(3):642-59. doi: 10.1016/j.jhep.2014.05.042. Epub 2014 Jul 8. No abstract available.
PubMed 25015420Bartolic M, Vovk A, Suput D. Effects of NH4CL application and removal on astrocytes and endothelial cells. Cell Mol Biol Lett. 2016 Aug 23;21:13. doi: 10.1186/s11658-016-0011-3. eCollection 2016.
PubMed 28536616Binesh N, Huda A, Bugbee M, Gupta R, Rasgon N, Kumar A, Green M, Han S, Thomas MA. Adding another spectral dimension to 1H magnetic resonance spectroscopy of hepatic encephalopathy. J Magn Reson Imaging. 2005 Apr;21(4):398-405. doi: 10.1002/jmri.20291.
PubMed 15779041Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013 Mar;58(3):593-608. doi: 10.1016/j.jhep.2012.12.005.
PubMed 23419824Bustamante J, Rimola A, Ventura PJ, Navasa M, Cirera I, Reggiardo V, Rodes J. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 1999 May;30(5):890-5. doi: 10.1016/s0168-8278(99)80144-5.
PubMed 10365817Chavarria L, Alonso J, Garcia-Martinez R, Simon-Talero M, Ventura-Cots M, Ramirez C, Torrens M, Vargas V, Rovira A, Cordoba J. Brain magnetic resonance spectroscopy in episodic hepatic encephalopathy. J Cereb Blood Flow Metab. 2013 Feb;33(2):272-7. doi: 10.1038/jcbfm.2012.173. Epub 2012 Nov 21.
PubMed 23168529Dale AM, Fischl B, Sereno MI. Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage. 1999 Feb;9(2):179-94. doi: 10.1006/nimg.1998.0395.
PubMed 9931268Elwir S, Rahimi RS. Hepatic Encephalopathy: An Update on the Pathophysiology and Therapeutic Options. J Clin Transl Hepatol. 2017 Jun 28;5(2):142-151. doi: 10.14218/JCTH.2016.00069. Epub 2017 May 4.
PubMed 28660152Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy--definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002 Mar;35(3):716-21. doi: 10.1053/jhep.2002.31250.
PubMed 11870389Fischl B, Dale AM. Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11050-5. doi: 10.1073/pnas.200033797.
PubMed 10984517Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, van der Kouwe A, Killiany R, Kennedy D, Klaveness S, Montillo A, Makris N, Rosen B, Dale AM. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron. 2002 Jan 31;33(3):341-55. doi: 10.1016/s0896-6273(02)00569-x.
PubMed 11832223Fischl B, Salat DH, van der Kouwe AJ, Makris N, Segonne F, Quinn BT, Dale AM. Sequence-independent segmentation of magnetic resonance images. Neuroimage. 2004;23 Suppl 1:S69-84. doi: 10.1016/j.neuroimage.2004.07.016.
PubMed 15501102Fischl B, Sereno MI, Dale AM. Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system. Neuroimage. 1999 Feb;9(2):195-207. doi: 10.1006/nimg.1998.0396.
PubMed 9931269Fischl B, Sereno MI, Tootell RB, Dale AM. High-resolution intersubject averaging and a coordinate system for the cortical surface. Hum Brain Mapp. 1999;8(4):272-84. doi: 10.1002/(sici)1097-0193(1999)8:43.0.co;2-4.
PubMed 10619420Fischl B, van der Kouwe A, Destrieux C, Halgren E, Segonne F, Salat DH, Busa E, Seidman LJ, Goldstein J, Kennedy D, Caviness V, Makris N, Rosen B, Dale AM. Automatically parcellating the human cerebral cortex. Cereb Cortex. 2004 Jan;14(1):11-22. doi: 10.1093/cercor/bhg087.
PubMed 14654453
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Magnetic Resonance Imaging in Detection of Minimal Hepatic Encephalopathy
- ClinicalTrials.gov ID
- NCT04131205
- Acronym / sponsor ID
- HepaticEncephalopathy
- Conditions
- Liver Cirrhoses, Hepatic Encephalopathy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Collaborators
- University of Ljubljana, Faculty of Medicine, Medical University of Graz, Johns Hopkins University
- Study start
- 1 Jun 2019 (actual)
- Primary completion
- 1 Jun 2023 (estimated)
- Study completion
- 1 Jun 2023 (estimated)
- First posted
- 18 Oct 2019 (actual)
- 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.
Introduction Liver cirrhosis (LC) is irreversible fibrosis of the liver (1) and it remains a public health problem. One of the complications of the cirrhosis is hepatic encephalopathy (HE) which is defined as brain dysfunction caused by liver insufficiency. Pathophysiological mechanisms of HE are complex and multifactorial. Recognition of beginning stages of HE, such as minimal HE (mHE) is of most importance.
Objectives and originality of the project Diagnosis of mHE can be challenging, time-consuming and, at least to some extent, subjective. This project will assess the role of magnetic resonance (MR) in mHE diagnosis with emphasis on multimodal imaging technique. With advanced magnetic resonance (MR) techniques, in-vivo detection of intracellular water content, estimation pH and metabolites levels with millimolar concentrations can be easily performed. This will offer to explore possible pathophysiological mechanisms of HE and to evaluate the results from previous, studies that were mainly performed on animal models or cell cultures.
By our best knowledge, multimodal MR approach as the investigators propose in this application has not been yet performed. The investigators will use advanced MR techniques which are currently not available in the clinical setting and require multicenter collaboration.
Methods The investigators will include 10-20 patients of both genders with hyperammonemia and mHE and 10-20 patients of both genders with HE. Diagnosis of HE will be made based on results of validated neuropsychiatric test. Age-matched and gender-matched control group with no gastrointestinal, neurological or psychiatric complaints and normal levels of ammonia in the blood. Patients with mHE/HE will be included from outpatient clinic of the Department of gastroenterology, University Medical Centre (UMC) Ljubljana. Healthy controls (HC) will be invited to join via internet advertisement. Contraindications for HC will include gastrointestinal (emphasis on liver disease), neurological or psychiatric complaints. Grade of mHE/HE will be classified according to West-Haven (WH) classification. Patients with different degree of liver cirrhosis, which will be scored with the Child-Pugh (CP) score, and with no contraindications for MR (e.g. presence of metal in body) will be included. Blood levels of liver enzymes and ammonia will be measured in all participants. MR scanning will include: T1- and T2-weighted MR, MRS (MEGA-PRESS and PRESS) in two voxels: striatum and cerebellum. Location will be double-checked by voxel position screenshots. Analysis, with voxel-positioning error compensation will be performed in Gannet (www.gabamrs.com). Moreover, high resolution diffusion weighted imaging (DWI), diffusion kurtosis imaging (DKI), quantitative susceptibility mapping (QSM) will be performed in brain as well. Liver QSM will be executed to assess iron load.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Minimal Hepatic Encephalopathy | – | Diagnostic Test: Magnetic Resonance ImagingPatients with hyperammonemia and minimal hepatic encephalopathy |
| Control | – | Diagnostic Test: Magnetic Resonance ImagingHealthy controls |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- We will include 10-20 patients of both genders with signs of hepatic encephalopathy and 10-20 patients of both genders without HE. Diagnosis of HE will be made based on results of validated neuropsychiatric test. Age-matched and gender-matched control group with no gastrointestinal, neurological or psychiatric complaints and normal levels of ammonia in the blood.
Key inclusion criteria (1 listed)
- Known liver disease/cirrhosis
Key exclusion criteria (1 listed)
- Pregnancy, non compatible material with MRI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnetic Resonance ImagingAlso: Ammonia Levels, Child Pugh Score, West-Haven grade of Hepatic EncephalopathyWe will assess the role of magnetic resonance (MR) in mHE diagnosis with emphasis on multimodal imaging technique | Diagnostic test | Control, Minimal Hepatic Encephalopathy |
Primary outcome
Structural and Functional Changes in Brain Structures with Magnetic Resonance Imaging
Time frame: 2 hours
GABA levels and other neurotransmitters with respect to the tissue water signal and corrected for tissue composition.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2019.
- Background: PubMed 25015420American Association for the Study of Liver Diseases; European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014 Sep;61(3):642-59. doi: 10.1016/j.jhep.2014.05.042. Epub 2014 Jul 8. No abstract available.
- Background: PubMed 28536616Bartolic M, Vovk A, Suput D. Effects of NH4CL application and removal on astrocytes and endothelial cells. Cell Mol Biol Lett. 2016 Aug 23;21:13. doi: 10.1186/s11658-016-0011-3. eCollection 2016.
- Background: PubMed 15779041Binesh N, Huda A, Bugbee M, Gupta R, Rasgon N, Kumar A, Green M, Han S, Thomas MA. Adding another spectral dimension to 1H magnetic resonance spectroscopy of hepatic encephalopathy. J Magn Reson Imaging. 2005 Apr;21(4):398-405. doi: 10.1002/jmri.20291.
- Background: PubMed 23419824Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013 Mar;58(3):593-608. doi: 10.1016/j.jhep.2012.12.005.
- Background: PubMed 10365817Bustamante J, Rimola A, Ventura PJ, Navasa M, Cirera I, Reggiardo V, Rodes J. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 1999 May;30(5):890-5. doi: 10.1016/s0168-8278(99)80144-5.
- Background: PubMed 23168529Chavarria L, Alonso J, Garcia-Martinez R, Simon-Talero M, Ventura-Cots M, Ramirez C, Torrens M, Vargas V, Rovira A, Cordoba J. Brain magnetic resonance spectroscopy in episodic hepatic encephalopathy. J Cereb Blood Flow Metab. 2013 Feb;33(2):272-7. doi: 10.1038/jcbfm.2012.173. Epub 2012 Nov 21.
- Background: PubMed 9931268Dale AM, Fischl B, Sereno MI. Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage. 1999 Feb;9(2):179-94. doi: 10.1006/nimg.1998.0395.
- Background: PubMed 28660152Elwir S, Rahimi RS. Hepatic Encephalopathy: An Update on the Pathophysiology and Therapeutic Options. J Clin Transl Hepatol. 2017 Jun 28;5(2):142-151. doi: 10.14218/JCTH.2016.00069. Epub 2017 May 4.
- Background: PubMed 11870389Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy--definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002 Mar;35(3):716-21. doi: 10.1053/jhep.2002.31250.
- Background: PubMed 10984517Fischl B, Dale AM. Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11050-5. doi: 10.1073/pnas.200033797.
- Background: PubMed 11832223Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, van der Kouwe A, Killiany R, Kennedy D, Klaveness S, Montillo A, Makris N, Rosen B, Dale AM. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron. 2002 Jan 31;33(3):341-55. doi: 10.1016/s0896-6273(02)00569-x.
- Background: PubMed 15501102Fischl B, Salat DH, van der Kouwe AJ, Makris N, Segonne F, Quinn BT, Dale AM. Sequence-independent segmentation of magnetic resonance images. Neuroimage. 2004;23 Suppl 1:S69-84. doi: 10.1016/j.neuroimage.2004.07.016.
- 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.
Sebastian Stefanovic, M.D. contact
Dusan Suput, M.D. study chair
Medical Faculty of Ljubljana
Borut Stabuc, M.D. study chair
Department of Gastroenterology and Hepatology, University Medical Centre Ljubljana
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 Liver Cirrhoses and Hepatic Encephalopathy, run by University Medical Centre Ljubljana at 1 site in Slovenia.
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 1 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 18 Oct 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 Slovenia. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gasper Zupan, M.D. (0038615437826, gasper.zupan@mf.uni-lj.si), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Structural and Functional Changes in Brain Structures with Magnetic Resonance Imaging (time frame: 2 hours). 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 NCT04131205, which also lists 30 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 18 Oct 2019.