Clinical trial NCT01556646: Effect of Tolvaptan on Cognitive Function in Cirrhosis
Official title: Effects of Tolvaptan on Cognitive Function, Brain Metabolism and Quality of Life in Hyponatremic Cirrhotics With Hepatic Encephalopathy: A Prospective Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cirrhosis
Hepatic Encephalopathy
Hyponatremia
Keywords: Cirrhosis
Hepatic Encephalopathy
Hyponatremia
Brain MRI
Health-related quality of life
cognitive function
Lead sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center
Sponsor class: FED
Collaborators: name: Otsuka America Pharmaceutical
First posted: 2012-03-16
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: Baseline assessment will include a

1. battery of eight cognitive tests
2. Health related quality of life
3. 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.

Eligibility criteria: 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

Primary outcomes:
measure: Cognitive performance
timeFrame: 14 days
Secondary outcomes:
measure: Brain MR Spectroscopy
timeFrame: 14 days
measure: Brain Diffusion Tensor Imaging
timeFrame: 14 days
measure: Health-related Quality of Life
timeFrame: 14 days
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center
state: Virginia
Study officials:
affiliation: Hunter Holmes McGuire VA Medical Center
name: Jasmohan S Bajaj, MD
role: PRINCIPAL_INVESTIGATOR
References: