Hepatic EncephalopathymHE-HHTNCT03586115
Minimal Hepatic Encephalopathy in Hereditary Hemorrhagic Telangiectasian
An observational study of Hepatic Encephalopathy and Minimal Brain Dysfunction, run by University of Bari at 1 site in Italy.
Trial summary
HHT or Rendu-Osler-Weber disease is a genetic disease with an autosomal dominant inheritance pattern, characterized by widespread telangiectases that can involve several organs including the intestinal tract and the liver. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hepatic Encephalopathy, Minimal Brain Dysfunction
- What is being tested?
- Critical flicker frequency assessment
- Type of treatment
- Medical device
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- 8 Jan 2018to 30 Apr 2020
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: All patients with a diagnosis of hereditary hemorragic telangectasia carrying micro or macro porto-systemic vascular shunts
Who may be able to join
- In this study all patients with hereditary hemorragic telangectasia carrying micro or macro porto-systemic vascular shunts will be enrolled.
Who cannot join
- Actual or previous presence of overt HE (West-Haven criteria) (1,2), gastrointestinal bleeding in the previous 2 weeks, significant comorbidities such as cardiac, respiratory or renal failure; previous transjugular intrahepatic portosystemic shunt, electrolyte imbalance as hyponatremia (Na<125 mg/dl), neurological diseases, color blindness or severe visual disturbances (cataracts, diabetic retinopathy), hepatocellular carcinoma or other malignancies, use of psychotropic drugs in the week prior to the study. Patients with advanced liver disease will also be excluded. Diagnosis of cirrhosis or advanced liver fibrosis will be based on: a) histological evaluation documented at any time before enrollment, b) liver transient elastography and c) a combination of clinical, laboratory and abdominal ultrasound parameters established a priori (Barone M et al. Digestive and Liver Disease 2018;50:496-500).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Minimal Hepatic Encephalopathy by a Neurophysiological Test in Patients With Hereditary Hemorrhagic Telangiectasia
HHT or Rendu-Osler-Weber disease is a genetic disease with an autosomal dominant inheritance pattern, characterized by widespread telangiectases that can involve several organs including the intestinal tract and the liver. Liver involvement by HHT is characterized by widespread diffuse liver vascular malformations that give origin to arteriovenous, arterioportal and portovenous shunts. The prevalence of hepatic involvement in HHT can reach 78%. Less commonly, patients may also develop porto-systemic encephalopathy (PSE). However, there are no studies on the possibility that patients with HHT might develop mHE, a highly plausible hypothesis considering the presence of diffuse macroscopic and microscopic porto-systemic shunt in this pathological condition.
Read the detailed description
Hepatic encephalopathy (HE) is a potentially reversible disorder characterized by neuropsychiatric abnormalities and motor disturbances that range from mild alterations of cognitive and motor functions to coma and death (1-2). This condition has been linked to the combination of gut flora alterations, which increase the production of gut-derived toxins such as ammonia and indoles, and porto-systemic shunts, leading to endotoxemia associated to systemic and cerebral inflammation (3-4). The subclinical expression of HE is defined minimal hepatic encephalopathy (mHE) (5-7). The latter condition is characterized by the presence of various quantifiable neurophysiological and neuropsychological deficits that are only recognized by the use of specific diagnostic tools such as the paper-and-pencil tests and its variants as well as critical flicker frequency (CFF) (8-11).
The visual test based on CFF measures the frequency (Hz) when impression of fused light turns to a flickering one (5,11). This neurophysiological test has an elevated specificity and reproducibility, with only little biases due to training effects and daytime variability (7,11-13). CFF has also shown the ability to predict the risk of developing overt HE in cirrhotics undergoing transjugular intrahepatic portosystemic shunt (TIPS) (14,15).
HHT or Rendu-Osler-Weber disease is a genetic disease with an autosomal dominant inheritance pattern, characterized by widespread telangiectases that can involve several organs including the intestinal tract and the liver (16). There are two main types of the disease, HHT1 and HHT2, which are caused respectively by mutations in ENG gene on chromosome 9 coding for endoglin for HHT1and mutations in ACVRL1 gene on chromosome 12 for HHT2 (17,18). These two types of the disease account for most clinical cases but mutations in MADH4 gene on chromosome 5 (encodingSMAD4), have been recently described, and a new type HHT3 has been reported (17). HHT2 is associated with a high rate of liver involvement (18).
Liver involvement by HHT is characterized by widespread diffuse liver vascular malformations that give origin to arteriovenous, arterioportal and portovenous shunts. The prevalence of hepatic involvement in HHT can reach 78% (19). Less commonly, patients may also develop porto-systemic encephalopathy (PSE) (20). However, there are no studies on the possibility that patients with HHT might develop mHE, a highly plausible hypothesis considering the presence of diffuse macroscopic and microscopic porto-systemic shunt in this pathological condition.
- Conditions
- Hepatic Encephalopathy, Minimal Brain Dysfunction
- Being tested
- Critical flicker frequency assessment
- Medical subject headings
- Hepatic Encephalopathy, Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Critical flicker frequency assessmentDevice
Also called Hepatic elastometry
All patients will undergo critical flicker frequency assessment to evaluate the presence of minimal hepatic encephalopaty. In addition, hepatic elastometry will be assessed to evaluate the presence of advanced liver fibrosis.
| Study group | Role | What they receive |
|---|---|---|
| Patients with Hereditary telangectasia | In addition to all laboratory analyses and imaging studies required to evaluate the disease, hepatic elastometry and critical flicker frequency assessment will be performed. Receives: Device: Critical flicker frequency assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minimal hepatic encephalopaty
This condition is not clinically evident and therefore it requires specific diagnostic tools (hepatonorm device: measures the critical flicker frequency; the measurement is expressed by Hz) to be diagnosed
Measured: one day
Secondary outcomes (1)
Liver fibrosis
The presence of advanced fibrosis can suggest the development of cirrhosis. Fibrosis is measured by hepatic elastometry and is expressed by kPa
Measured: one day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2018
- Study start8 Jan 2018
- Primary completion21 Mar 2020
- Study completion30 Apr 2020
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 Hepatic EncephalopathyStudies 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
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Bari
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michele Barone, University of Bari
- Investigators
- michele barone, MD, PhD, Principal investigator, University of Bari
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03586115
- Sponsor's protocol ID
- Policlinic Hospital 4, Bari
- Acronym
- mHE-HHT
- Status last verified
- Nov 2020
- First submitted
- 2 Jul 2018
- Last updated
- 3 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Barone M, Shahini E, Iannone A, Viggiani MT, Corvace V, Principi M, Di Leo A. Critical flicker frequency test predicts overt hepatic encephalopathy and survival in patients with liver cirrhosis. Dig Liver Dis. 2018 May;50(5):496-500. doi: 10.1016/j.dld.2018.01.133. Epub 2018 Jan 31.
PubMed 29530628
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Minimal Hepatic Encephalopathy by a Neurophysiological Test in Patients With Hereditary Hemorrhagic Telangiectasia
- ClinicalTrials.gov ID
- NCT03586115
- Acronym / sponsor ID
- mHE-HHT / Policlinic Hospital 4, Bari
- Conditions
- Hepatic Encephalopathy, Minimal Brain Dysfunction
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of BariUniversity, hospital or other
- Study start
- 8 Jan 2018 (actual)
- Primary completion
- 21 Mar 2020 (actual)
- Study completion
- 30 Apr 2020 (actual)
- First posted
- 13 Jul 2018 (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.
HHT or Rendu-Osler-Weber disease is a genetic disease with an autosomal dominant inheritance pattern, characterized by widespread telangiectases that can involve several organs including the intestinal tract and the liver. Liver involvement by HHT is characterized by widespread diffuse liver vascular malformations that give origin to arteriovenous, arterioportal and portovenous shunts. The prevalence of hepatic involvement in HHT can reach 78%. Less commonly, patients may also develop porto-systemic encephalopathy (PSE). However, there are no studies on the possibility that patients with HHT might develop mHE, a highly plausible hypothesis considering the presence of diffuse macroscopic and microscopic porto-systemic shunt in this pathological condition.
Detailed description
Hepatic encephalopathy (HE) is a potentially reversible disorder characterized by neuropsychiatric abnormalities and motor disturbances that range from mild alterations of cognitive and motor functions to coma and death (1-2). This condition has been linked to the combination of gut flora alterations, which increase the production of gut-derived toxins such as ammonia and indoles, and porto-systemic shunts, leading to endotoxemia associated to systemic and cerebral inflammation (3-4). The subclinical expression of HE is defined minimal hepatic encephalopathy (mHE) (5-7). The latter condition is characterized by the presence of various quantifiable neurophysiological and neuropsychological deficits that are only recognized by the use of specific diagnostic tools such as the paper-and-pencil tests and its variants as well as critical flicker frequency (CFF) (8-11).
The visual test based on CFF measures the frequency (Hz) when impression of fused light turns to a flickering one (5,11). This neurophysiological test has an elevated specificity and reproducibility, with only little biases due to training effects and daytime variability (7,11-13). CFF has also shown the ability to predict the risk of developing overt HE in cirrhotics undergoing transjugular intrahepatic portosystemic shunt (TIPS) (14,15).
HHT or Rendu-Osler-Weber disease is a genetic disease with an autosomal dominant inheritance pattern, characterized by widespread telangiectases that can involve several organs including the intestinal tract and the liver (16). There are two main types of the disease, HHT1 and HHT2, which are caused respectively by mutations in ENG gene on chromosome 9 coding for endoglin for HHT1and mutations in ACVRL1 gene on chromosome 12 for HHT2 (17,18). These two types of the disease account for most clinical cases but mutations in MADH4 gene on chromosome 5 (encodingSMAD4), have been recently described, and a new type HHT3 has been reported (17). HHT2 is associated with a high rate of liver involvement (18).
Liver involvement by HHT is characterized by widespread diffuse liver vascular malformations that give origin to arteriovenous, arterioportal and portovenous shunts. The prevalence of hepatic involvement in HHT can reach 78% (19). Less commonly, patients may also develop porto-systemic encephalopathy (PSE) (20). However, there are no studies on the possibility that patients with HHT might develop mHE, a highly plausible hypothesis considering the presence of diffuse macroscopic and microscopic porto-systemic shunt in this pathological condition.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with Hereditary telangectasia | – | Device: Critical flicker frequency assessmentIn addition to all laboratory analyses and imaging studies required to evaluate the disease, hepatic elastometry and critical flicker frequency assessment will be performed. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All patients with a diagnosis of hereditary hemorragic telangectasia carrying micro or macro porto-systemic vascular shunts
Key inclusion criteria (1 listed)
- In this study all patients with hereditary hemorragic telangectasia carrying micro or macro porto-systemic vascular shunts will be enrolled.
Key exclusion criteria (1 listed)
- Actual or previous presence of overt HE (West-Haven criteria) (1,2), gastrointestinal bleeding in the previous 2 weeks, significant comorbidities such as cardiac, respiratory or renal failure; previous transjugular intrahepatic portosystemic shunt, electrolyte imbalance as hyponatremia (Na<125 mg/dl), neurological diseases, color blindness or severe visual disturbances (cataracts, diabetic retinopathy), hepatocellular carcinoma or other malignancies, use of psychotropic drugs in the week prior to the study. Patients with advanced liver disease will also be excluded. Diagnosis of cirrhosis or advanced liver fibrosis will be based on: a) histological evaluation documented at any time before enrollment, b) liver transient elastography and c) a combination of clinical, laboratory and abdominal ultrasound parameters established a priori (Barone M et al. Digestive and Liver Disease 2018;50:496-500).
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 |
|---|---|---|
| Critical flicker frequency assessmentAlso: Hepatic elastometryAll patients will undergo critical flicker frequency assessment to evaluate the presence of minimal hepatic encephalopaty. In addition, hepatic elastometry will be assessed to evaluate the presence of advanced liver fibrosis. | Device | Patients with Hereditary telangectasia |
Primary outcome
Minimal hepatic encephalopaty
Time frame: one day
This condition is not clinically evident and therefore it requires specific diagnostic tools (hepatonorm device: measures the critical flicker frequency; the measurement is expressed by Hz) to be diagnosed
1 secondary outcome
Liver fibrosis
Time frame: one day
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 3 Nov 2020.
- Background: PubMed 29530628Barone M, Shahini E, Iannone A, Viggiani MT, Corvace V, Principi M, Di Leo A. Critical flicker frequency test predicts overt hepatic encephalopathy and survival in patients with liver cirrhosis. Dig Liver Dis. 2018 May;50(5):496-500. doi: 10.1016/j.dld.2018.01.133. Epub 2018 Jan 31.
- 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.
michele barone, MD, PhD principal investigator
University of Bari
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 Hepatic Encephalopathy and Minimal Brain Dysfunction, run by University of Bari at 1 site in Italy.
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: finished, as of the sponsor's last update on 3 Nov 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 Italy. 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?
Minimal hepatic encephalopaty (time frame: one day). 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 NCT03586115, 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 3 Nov 2020.