Effect of Tolvaptan on Cognitive Function in Cirrhosis

Hunter Holmes Mcguire Veteran Affairs Medical Center

Status and phase: Completed; Phase 3

Conditions: Hepatic Encephalopathy; Cirrhosis; Hyponatremia

Treatments: Drug: Tolvaptan

Study type: Interventional

Funder types: Other U.S. Federal agency; Industry

Identifiers

NCT01556646

Bajaj 01720

Details and patient eligibility

About

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

Full 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.

Enrollment: 25 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

Tolvaptan

Experimental group

Description:

Open label study of tolvaptan. First 3 days as an inpatient then outpatient for the remainder of the study

Treatment:

Drug: Tolvaptan