Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 31, 2018
Sponsor:
Information provided by (Responsible Party):
Michele Barone, University of Bari

Brief 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. 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.

Condition or disease Intervention/treatment
Hepatic Encephalopathy Minimal Brain Dysfunction Device: Critical flicker frequency assessment

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.


Layout table for study information
Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Other
Time Perspective: Cross-Sectional
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 : October 13, 2018
Estimated Study Completion Date : December 31, 2018


Group/Cohort Intervention/treatment
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All patients with a diagnosis of hereditary hemorragic telangectasia carrying micro or macro porto-systemic vascular shunts
Criteria

Inclusion Criteria:

  • In this study all patients with hereditary hemorragic telangectasia carrying micro or macro porto-systemic vascular shunts will be enrolled.

Exclusion Criteria:

  • 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).

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): NCT03586115


Contacts
Layout table for location contacts
Contact: michele barone, MD, PhD 01100390805591111 ext 3514 michele.barone@uniba.it
Contact: Alfredo Di Leo, MD, PhD 01100390805591111 ext 2577 alfredo.dileo@uniba.it

Locations
Layout table for location information
Italy
Policlinic Hospital Recruiting
Bari, Italy, 70124
Contact: Michele Barone, MD, PhD    011-39-0805593514    michele.barone@uniba.it   
Sponsors and Collaborators
University of Bari
Investigators
Layout table for investigator information
Principal Investigator: michele barone, MD, PhD University of Bari

Publications:
Layout table for additonal information
Responsible Party: Michele Barone, Clinical professor, University of Bari
ClinicalTrials.gov Identifier: NCT03586115     History of Changes
Other Study ID Numbers: Policlinic Hospital 4, Bari
First Posted: July 13, 2018    Key Record Dates
Last Update Posted: July 31, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Brain Diseases
Telangiectasia, Hereditary Hemorrhagic
Attention Deficit Disorder with Hyperactivity
Central Nervous System Diseases
Nervous System Diseases
Liver Diseases
Digestive System Diseases
Brain Diseases, Metabolic
Metabolic Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Hematologic Diseases
Attention Deficit and Disruptive Behavior Disorders
Neurodevelopmental Disorders
Mental Disorders
Hepatic Encephalopathy
Liver Failure
Hepatic Insufficiency
Telangiectasis
Vascular Malformations
Cardiovascular Abnormalities
Congenital Abnormalities