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Minimal Hepatic Encephalopathy in Hereditary Hemorrhagic Telangiectasian (mHE-HHT)

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ClinicalTrials.gov Identifier: NCT03586115
Recruitment Status : Recruiting
First Posted : July 13, 2018
Last Update Posted : July 8, 2019
Sponsor:
Information provided by (Responsible Party):
Michele Barone, University of Bari

Tracking Information
First Submitted Date July 2, 2018
First Posted Date July 13, 2018
Last Update Posted Date July 8, 2019
Actual Study Start Date January 8, 2018
Estimated Primary Completion Date September 23, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 13, 2018)
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
Original Primary Outcome Measures
 (submitted: July 12, 2018)
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) to be diagnosed
Change History Complete list of historical versions of study NCT03586115 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: July 13, 2018)
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
Original Secondary Outcome Measures
 (submitted: July 12, 2018)
Liver fibrosis [ Time Frame: one day ]
The presence of advanced fibrosis can suggest the development of cirrhosis
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Minimal Hepatic Encephalopathy in Hereditary Hemorrhagic Telangiectasian
Official Title Evaluation of Minimal Hepatic Encephalopathy by a Neurophysiological Test in Patients With Hereditary Hemorrhagic Telangiectasia
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.
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 Type Observational
Study Design Observational Model: Other
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population All patients with a diagnosis of hereditary hemorragic telangectasia carrying micro or macro porto-systemic vascular shunts
Condition
  • Hepatic Encephalopathy
  • Minimal Brain Dysfunction
Intervention 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
Study Groups/Cohorts 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.
Intervention: Device: Critical flicker frequency assessment
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 12, 2018)
50
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 31, 2019
Estimated Primary Completion Date September 23, 2019   (Final data collection date for primary outcome measure)
Eligibility 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).
Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
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
Listed Location Countries Italy
Removed Location Countries  
 
Administrative Information
NCT Number NCT03586115
Other Study ID Numbers Policlinic Hospital 4, Bari
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Michele Barone, University of Bari
Study Sponsor University of Bari
Collaborators Not Provided
Investigators
Principal Investigator: michele barone, MD, PhD University of Bari
PRS Account University of Bari
Verification Date July 2019