Study Stopped
No subjects were able to be recruited for the study.
Treatment of Hepatic Encephalopathy With Flumazenil and Change in Cortical GABA Levels in MRS
2 other identifiers
interventional
N/A
1 country
1
Brief Summary
The purpose of this study is to test feasibility of measuring flumazenil-induced changes in cortical GABA levels observed with localized 1H-MRS in relation to changes in severity of hepatic encephalopathy (HE) in subjects with non-alcoholic liver cirrhosis. This study is a double-blind, placebo-controlled, randomized, cross-over design.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Jun 2014
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 27, 2014
CompletedFirst Posted
Study publicly available on registry
January 29, 2014
CompletedStudy Start
First participant enrolled
June 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2017
CompletedJuly 7, 2020
July 1, 2020
3.3 years
January 27, 2014
July 3, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
hepatic encephalopathy symptoms
To assess flumazenil-induced changes in cortical GABA levels, observed with localized proton magnetic resonance spectroscopy (1H-MRS) using a 4-Tesla imaging spectrometer in relation to changes in hepatic encephalopathy. MRS is a non-invasive imaging technique that allows examination of metabolic changes and biochemical information about the target brain tissues without the need for a biopsy. Hepatic encephalopathy will be measured using neuropsychological tests. These tests include Benton scoring, Hopkins Verbal Learning Test trials and delayed recall and recognition trials, Smith symbol digits, simple auditory sustained attention continuous performance test, digit span sequencing, Wechsler Adult Intelligence Scale-III symbol search, cancellation tasks, line orientation, serial 3s subtraction, Hooper visual orientation test, Trail Making Tests A \& B, and orientation retest. Variables will be transformed so that higher scores indicate better cognitive function.
one year
Secondary Outcomes (2)
hepatic encephalopathy symptoms
one year
flumazenil impact on functional MRI
one year
Study Arms (2)
Flumazenil
EXPERIMENTALA priming dose bolus of 0.4 mg of flumazenil will be administered intravenously (Minute 0). At this time the 1H-MRS scan will begin. Over the next 6 minutes, a drip infusion of flumazenil will be administered to the patient at a rate of 0.1 mg flumazenil per minute for a total of 7 doses during the scan. Total dose will be 1.0 mg.
Saline
PLACEBO COMPARATORA priming dose bolus of 0.4 mg of placebo will be administered intravenously (Minute 0). At this time the 1H-MRS scan will begin. Over the next 6 minutes, a drip infusion of placebo mixed with saline will be administered to the patient at a rate of 0.1 mg per minute for a total of 7 doses during the scan. Total dose will be 1.0 mg.
Interventions
A priming dose bolus of 0.4 mg of flumazenil will be administered intravenously (Minute 0). At this time the 1H-MRS scan will begin. Over the next 6 minutes, a drip infusion of placebo mixed with saline will be administered to the patient at a rate of 0.1 mg per minute for a total of 7 doses during the scan. Total dose will be 1.0 mg.
A priming dose bolus of 0.4 mg of placebo will be administered intravenously (Minute 0). At this time the 1H-MRS scan will begin. Over the next 6 minutes, a drip infusion of placebo mixed with saline will be administered to the patient at a rate of 0.1 mg per minute for a total of 7 doses during the scan. Total dose will be 1.0 mg.
Eligibility Criteria
You may qualify if:
- Age: 18 and older
- ICD-9 diagnosis of hepatic encephalopathy
- Ability to feel comfortable in confined areas (like MRI)
- Ability to provide informed consent
- Speaks fluent English without any communication barriers
- Reliable family member or friend able to stay with participant during abstinence from HE medication prior to visit.
You may not qualify if:
- Current DSM-IV-R diagnosis of Alcohol or Other Drug Abuse or Dependence
- Positive screen for alcohol abuse as determined by the CAGE questionnaire
- Positive urine toxicity screen for benzodiazepine medications or illicit drugs
- History of long-term use of benzodiazepine medications
- Current use of non-benzodiazepine agonist medications
- History of Panic Disorder
- History of any Psychotic Disorder
- History of seizures and/or Seizure Disorder
- History of dysrhythmia, cardiovascular collapse, or recent head trauma
- History of side effects from anticholinergic medications
- History of cyclic antidepressant overdose or poisoning
- Pregnant or nursing
- Resides in nursing home or other long-term care facility
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Yale Psychological Medicine Research Center
New Haven, Connecticut, 06520, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Hochang B Lee, MD
Yale University
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 27, 2014
First Posted
January 29, 2014
Study Start
June 1, 2014
Primary Completion
October 1, 2017
Study Completion
October 1, 2017
Last Updated
July 7, 2020
Record last verified: 2020-07