Minimal Hepatic Encephalopathy in Hereditary Hemorrhagic Telangiectasian (mHE-HHT)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03586115|
Recruitment Status : Recruiting
First Posted : July 13, 2018
Last Update Posted : July 8, 2019
|Condition or disease||Intervention/treatment|
|Hepatic Encephalopathy Minimal Brain Dysfunction||Device: Critical flicker frequency assessment|
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 Type :||Observational|
|Estimated Enrollment :||50 participants|
|Official Title:||Evaluation of Minimal Hepatic Encephalopathy by a Neurophysiological Test in Patients With Hereditary Hemorrhagic Telangiectasia|
|Actual Study Start Date :||January 8, 2018|
|Estimated Primary Completion Date :||September 23, 2019|
|Estimated Study Completion Date :||December 31, 2019|
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.
Device: Critical flicker frequency assessment
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.
Other Name: Hepatic elastometry
- 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
- Liver fibrosis [ Time Frame: one day ]The presence of advanced fibrosis can suggest the development of cirrhosis. Fibrosis is measured by hepatic elastometry and is expressed by kPa
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): NCT03586115
|Contact: michele barone, MD, PhD||01100390805591111 ext email@example.com|
|Contact: Alfredo Di Leo, MD, PhD||01100390805591111 ext firstname.lastname@example.org|
|Bari, Italy, 70124|
|Contact: Michele Barone, MD, PhD 011-39-0805593514 email@example.com|
|Principal Investigator:||michele barone, MD, PhD||University of Bari|