EYE-Mobile TRACKer IN the Diagnosis of Minimal Hepatic Encephalopathy
- Conditions
- Cirrhosis
- Interventions
- Device: Eye-tracker Mobile EBT
- Registration Number
- NCT03732118
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
Hepatic encephalopathy (HE) corresponds to the neurological or the neuropsychological symptoms caused by an acute or chronic liver disease and/or porto-systemic shunt. Many patients present neurological symptoms even if their liver disease is stabilized. Furthermore, HE is associated with an altered quality of life and an increased mortality. Its incidence is high with 30 to 80% of cirrhotic patients that will display according to retained diagnostic criteria. HE symptoms are going from subtle neuropsychological abnormalities detected only on neuropsychological testing, minimal HE, to altered consciousness, overt HE. Recently, the therapeutic armamentarium has increased with now several drugs (rifaximin, ammonia lowering agents) that are able to prevent new bouts of HE. Unfortunately, the diagnosis of minimal HE is difficult and no gold-standard is available. None of the proposed test is rapid and easily performed at bedside.
Recently, different studies suggest the potential interest of the study of the ocular movements in HE. Abnormalities in ocular saccades could be an early predictor of cortical impairment. In a pilot feasibility study using an eye-tracker, we could show that cirrhotic patients with minimal HE had, compared to healthy controls, increased latencies, decreased speed of voluntary and reflex saccades, more errors in anti-saccades, more anticipations saccades and more difficulties to fix the target.
Our hypothesis was that the use of the eye-tracker will enable the diagnosis of minimal HE by studying the characteristics of saccades and anti-saccades.
Since no gold-standard is available for the diagnosis of minimal HE, we will use the conclusion of an adjudication committee formed by 2 experts. Their clinical judgment will take into account the results of medical history, clinical examination, neuropsychological testing, PHES, Critical Flicker Frequency test (CFF), ammonemia levels, EEG and brain MRI with spectroscopy.
- Detailed Description
Hepatic encephalopathy (HE) corresponds to the neurological or the neuropsychological symptoms caused by an acute or chronic liver disease and/or porto-systemic shunt. Many patients present neurological symptoms even if their liver disease is stabilized. Furthermore, HE is associated with an altered quality of life and an increased mortality. Its incidence is high with 30 to 80% of cirrhotic patients that will display according to retained diagnostic criteria. HE symptoms are going from subtle neuropsychological abnormalities detected only on neuropsychological testing, minimal HE, to altered consciousness, overt HE. Recently, the therapeutic armamentarium has increased with now several drugs (rifaximine, ammonia lowering agents) that are able to prevent new bouts of HE. Unfortunately, the diagnosis of minimal HE is difficult and no gold-standard is available. None of the proposed test is rapid and easily performed at bedside.
Recently, different studies suggest the potential interest of the study of the ocular movements in HE. Abnormalities in ocular saccads could be an early predictor of cortical impairment. In a pilot feasibility study using an eye-tracker, we could show that cirrhotic patients with minimal HE had, compared to healthy controls, increased latencies, decreased speed of voluntary and reflex saccads, more errors in anti-saccads, more anticipations saccads and more difficulties to fix the target.
Our hypothesis was that the use of the eye-tracker will enable the diagnosis of minimal HE by studying the characteristics of saccads and anti-saccads.
Since no gold-standard is available for the diagnosis of minimal HE, we will use the conclusion of an adjudication committee formed by 2 experts. Their clinical judgment will take into account the results of medical history, clinical examination, neuropsychological testing, PHES, Critical Flicker Frequency test (CFF), ammonemia levels, EEG and brain MRI with spectroscopy.
Gold standard definition: diagnostic of minimal HE as stated by adjudication committee composed of 2 experts. Each patient will be classified as : patient without EH (neither clinical or minimal) and patient with EHM. The results of medical history, clinical examination, EEG results (triphasic waves, decreased frequency), ammonia level (above 50mcmol/L or not), neuropsychological testing encompassing PHES (below -4 or not) and CFF (below 39Hz or not), brain MRI with MR-spectroscopy (HE profile on MRS) will be aggregated to obtain their adjudication. All the tests will be performed by trained personal aware of the evaluation of cirrhotic patients with possible HE. The eye-tracking evaluation will be blinded to the conclusion of the adjudication committee (presence or absence of HE).
Since the data from the eye-tracker are quantitative, a ROC curve will be used to evaluate the diagnostic performance of each parameters measured by the study device (mainly, saccads latencies, voluntary and reflexes ones, and the percentage of errors in saccads, anti-saccads and voluntary anticipations).
The ability of each measure to diagnose minimal HE will be evaluated by the area under the ROC and its 95% confidence interval. Sensibility, specificity, positive and negative predictive values will be given for each possible cut-off with their 95% confidence interval. In order to optimize the diagnostic performance, the most discriminating values will be used to build a multivariate diagnostic model. To prevent overfitting frequently associated with "standard" logistic regression, the selection of variables of interest will be performed with the LASSO method. This method is valuable when the number of subjects are limited.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 30
Eligibility criteria for EHM+ subjects:
- Age between 18 and 70 (inclusive)
- Cirrhosis
- Minimal hepatic encephalopathy
- Expression of non opposition
Eligibility criteria for EHM- subjects:
- Age between 18 and 70 (inclusive)
- Cirrhosis
- No hepatic encephalopathy (minimal or clinical)
- Paired with EHM+ subjects about age, gender, MELD score and cirrhosis etiology
- Expression of non opposition
Exclusion Criteria for all subjects:
- Age older than 70
- MMS score < 24
- Clinical hepatic encephalopathy
- Cirrhosis etiology different from alcoholic, viral or metabolic one
- Intake of psychotropic drugs within 48h
- Alcohol intake > 30 g/j
- Heart, renal or respiratory failure
- Evolutive neurological diseases
- History of neurological diseases causing consequences
- Non corrected visuals disorders
- Oculomotor disorders from any etiology
- Highly-resistant bacteria carrier subjects
- Inability to put on the eye-tracker device
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description No hepatic encephalopathy (minimal or clinical) Eye-tracker Mobile EBT - Minimal hepatic encephalopathy Eye-tracker Mobile EBT -
- Primary Outcome Measures
Name Time Method Diagnostic performance (evaluated with the area under the roc curve) associated with the measure of reflex saccads latencies for the diagnostic of minimal HE one day The diagnostic performance of the measure of reflex saccads latencies will be evaluated by the area under the roc curve and its 95% confidence interval
- Secondary Outcome Measures
Name Time Method Area under the roc curve associated with the measure of reflex saccads gain for the diagnostic of minimal HE one day The diagnostic performance of the measure of reflex saccads gain will be evaluated by the area under the roc curve and its 95% confidence interval.
Association between reflex saccads gain and results of neuropsychological testings one day Association between reflex saccads speed and results of neuropsychological testings one day Association between voluntary saccads gain and results of neuropsychological testings one day Area under the roc curve associated with the measure of percentage of errors in saccads for the diagnostic of minimal HE. one day The diagnostic performance of the measure of percentage of errors in saccads will be evaluated by the area under the roc curve and its 95% confidence interval.
Association between percentage of errors in anti-saccads and results of neuropsychological testings one day Area under the roc curve associated with the measure of reflex saccads speed for the diagnostic of minimal HE. one day The diagnostic performance of the measure of reflex saccads speed will be evaluated by the area under the roc curve and its 95% confidence interval.
Area under the roc curve associated with the measure of voluntary saccads latency for the diagnostic of minimal HE. one day The diagnostic performance of the measure of voluntary saccads latency will be evaluated by the area under the roc curve and its 95% confidence interval.
Association between voluntary saccads latency and results of neuropsychological testings one day Area under the roc curve associated with the measure of voluntary saccads gain for the diagnostic of minimal HE. one day The diagnostic performance of the measure of voluntary saccads gain will be evaluated by the area under the roc curve and its 95% confidence interval.
Association between voluntary saccads anticipation and results of neuropsychological testings one day Area under the roc curve associated with the measure of voluntary saccads anticipation for the diagnostic of minimal HE. one day The diagnostic performance of the measure of voluntary saccads anticipation will be evaluated by the area under the roc curve and its 95% confidence interval.
Association between percentage of errors in saccads and results of neuropsychological testings one day Area under the roc curve associated with the measure of percentage of errors in anti-saccads for the diagnostic of minimal HE one day The diagnostic performance of the measure of percentage of errors in anti-saccads will be evaluated by the area under the roc curve and its 95% confidence interval.
Trial Locations
- Locations (1)
Pitié-Salpêtrière Hospital
🇫🇷Paris, France