Effect of Tolvaptan on Cognitive Function in Cirrhosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01556646
Recruitment Status : Completed
First Posted : March 16, 2012
Last Update Posted : February 7, 2014
Otsuka America Pharmaceutical
Information provided by (Responsible Party):
Jasmohan Bajaj, Hunter Holmes Mcguire Veteran Affairs Medical Center

March 15, 2012
March 16, 2012
February 7, 2014
April 2011
June 2013   (Final data collection date for primary outcome measure)
Cognitive performance [ Time Frame: 14 days ]
Same as current
Complete list of historical versions of study NCT01556646 on Archive Site
  • Brain MR Spectroscopy [ Time Frame: 14 days ]
  • Brain Diffusion Tensor Imaging [ Time Frame: 14 days ]
  • Health-related Quality of Life [ Time Frame: 14 days ]
Same as current
Not Provided
Not Provided
Effect of Tolvaptan on Cognitive Function in Cirrhosis
Effects of Tolvaptan on Cognitive Function, Brain Metabolism and Quality of Life in Hyponatremic Cirrhotics With Hepatic Encephalopathy: A Prospective Clinical Trial
Hypothesis: Tolvaptan will improve cognitive function, brain edema and health-related quality of life in cirrhotic patients with hyponatremia

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.

Phase 3
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Cirrhosis
  • Hepatic Encephalopathy
  • Hyponatremia
Drug: Tolvaptan
15 to 30mg qd titrated to sodium concentration
Other Name: Samsca
Experimental: Tolvaptan
Open label study of tolvaptan. First 3 days as an inpatient then outpatient for the remainder of the study
Intervention: Drug: Tolvaptan
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
June 2013
June 2013   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
Bajaj 01720
Not Provided
Not Provided
Jasmohan Bajaj, Hunter Holmes Mcguire Veteran Affairs Medical Center
Hunter Holmes Mcguire Veteran Affairs Medical Center
Otsuka America Pharmaceutical
Principal Investigator: Jasmohan S Bajaj, MD Hunter Holmes McGuire VA Medical Center
Hunter Holmes Mcguire Veteran Affairs Medical Center
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP