Effect of Tolvaptan on Cognitive Function in Cirrhosis

NCT ID: NCT01556646

Last Updated: 2014-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2013-06-30

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.

Conditions

Cirrhosis; Hepatic Encephalopathy; Hyponatremia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tolvaptan

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

Group Type: EXPERIMENTAL

Tolvaptan

Intervention Type: DRUG

15 to 30mg qd titrated to sodium concentration

Interventions

Tolvaptan

15 to 30mg qd titrated to sodium concentration

Intervention Type: DRUG

Other Intervention Names

Samsca

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka America Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

Hunter Holmes Mcguire Veteran Affairs Medical Center

FED

Sponsor Role: lead

Responsible Party

Jasmohan Bajaj

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jasmohan S Bajaj, MD

Role: PRINCIPAL_INVESTIGATOR

Hunter Holmes McGuire VA Medical Center

Locations

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, United States

Countries

United States

Other Identifiers

Bajaj 01720

Identifier Type: -

Identifier Source: org_study_id