Effect of Tolvaptan on Cognitive Function in Cirrhosis

Study Overview
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Brief Summary
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Hypothesis: Tolvaptan will improve cognitive function, brain edema and health-related quality of life in cirrhotic patients with hyponatremia

Detailed Description
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Baseline assessment will include a battery of eight cognitive tests Health related quality of life MRI head evaluating MR spectroscopy and diffusion tensor imaging Patients will then be given tolvaptan 15-30mg qd for 14 days after which the tests will be repeated. During the first 3 days of tolvaptan administration, patients will be admitted and serum sodium will be drawn every 8 hours. 24 hr urine collection will also be performed. Between the initiation and end of tolvaptan, patients will be seen at least every 3-5 days in between. Participation will be terminated in case patients get transplanted or develop overt HE in between.

Official Title
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Effects of Tolvaptan on Cognitive Function, Brain Metabolism and Quality of Life in Hyponatremic Cirrhotics With Hepatic Encephalopathy: A Prospective Clinical Trial

Conditions
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Cirrhosis, Hepatic Encephalopathy, Hyponatremia

Intervention / Treatment
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* Drug: Tolvaptan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cirrhosis diagnosed by liver biopsy or radiological evidence of nodular cirrhotic liver or varices on endoscopy or laboratory features (platelet count <150,000 with an AST/ALT ratio >1). History of HE controlled on lactulose and/or rifaximin Last HE episode >2 months prior to enrollment and <2 episodes within 6 months Mini-mental status exam score ≥25 Serum sodium <130mg/dl within the last 14 days and the day of enrollment Availability of a caregiver Able to undergo MR of the head Exclusion Criteria: Uncontrolled HE manifested by MMSE <25 Alcohol abuse within 3 months Illicit drug use within 3 months Psychoactive drug use other than regularly scheduled anti-depressants or methadone. Contraindication to MR examination (see attached MRI Safety Form) Placement of a transjugular intra-hepatic portosystemic shunt (TIPS) Creatinine Clearance less than 10 ml/min or undergoing hemodialysis HIV infection Use of azole medications Pregnancy Current use of tolvaptan, hypertonic saline or other medical therapies for hyponatremia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tolvaptan<br>Open label study of tolvaptan. First 3 days as an inpatient then outpatient for the remainder of the study | Drug: Tolvaptan<br>* 15 to 30mg qd titrated to sodium concentration<br>* Other names: Samsca;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive performance |  | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain MR Spectroscopy |  | 14 days | 
| Brain Diffusion Tensor Imaging |  | 14 days | 
| Health-related Quality of Life |  | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cirrhosis, Hepatic Encephalopathy, Hyponatremia, Brain MRI, Health-related quality of life, cognitive function