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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

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

Condition or disease Intervention/treatment Phase
Cirrhosis Hepatic Encephalopathy Hyponatremia Drug: Tolvaptan Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : April 2011
Actual Primary Completion Date : June 2013
Actual Study Completion Date : June 2013

Arm Intervention/treatment
Experimental: Tolvaptan
Open label study of tolvaptan. First 3 days as an inpatient then outpatient for the remainder of the study
Drug: Tolvaptan
15 to 30mg qd titrated to sodium concentration
Other Name: Samsca

Primary Outcome Measures :
  1. Cognitive performance [ Time Frame: 14 days ]

Secondary Outcome Measures :
  1. Brain MR Spectroscopy [ Time Frame: 14 days ]
  2. Brain Diffusion Tensor Imaging [ Time Frame: 14 days ]
  3. Health-related Quality of Life [ Time Frame: 14 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01556646

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United States, Virginia
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, United States, 23249
Sponsors and Collaborators
Hunter Holmes Mcguire Veteran Affairs Medical Center
Otsuka America Pharmaceutical
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Principal Investigator: Jasmohan S Bajaj, MD Hunter Holmes McGuire VA Medical Center

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Responsible Party: Jasmohan Bajaj, Associate Professor of Medicine, Hunter Holmes Mcguire Veteran Affairs Medical Center Identifier: NCT01556646     History of Changes
Other Study ID Numbers: Bajaj 01720
First Posted: March 16, 2012    Key Record Dates
Last Update Posted: February 7, 2014
Last Verified: February 2014
Keywords provided by Jasmohan Bajaj, Hunter Holmes Mcguire Veteran Affairs Medical Center:
Hepatic Encephalopathy
Brain MRI
Health-related quality of life
cognitive function
Additional relevant MeSH terms:
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Liver Cirrhosis
Hepatic Encephalopathy
Brain Diseases
Pathologic Processes
Liver Diseases
Digestive System Diseases
Central Nervous System Diseases
Nervous System Diseases
Liver Failure
Hepatic Insufficiency
Brain Diseases, Metabolic
Metabolic Diseases
Water-Electrolyte Imbalance
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Physiological Effects of Drugs