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Effect of Tolvaptan on Cognitive Function in Cirrhosis

This study is currently recruiting participants.
Verified December 2012 by Hunter Holmes Mcguire Veteran Affairs Medical Center
Sponsor:
Collaborator:
Otsuka America Pharmaceutical
Information provided by (Responsible Party):
Jasmohan Bajaj, Hunter Holmes Mcguire Veteran Affairs Medical Center
ClinicalTrials.gov Identifier:
NCT01556646
First received: March 15, 2012
Last updated: December 10, 2012
Last verified: December 2012
History of Changes
  Purpose

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


Condition Intervention Phase
Cirrhosis
Hepatic Encephalopathy
Hyponatremia
 Drug: Tolvaptan
 Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cirrhosis
Drug Information available for: Tolvaptan
U.S. FDA Resources

Further study details as provided by Hunter Holmes Mcguire Veteran Affairs Medical Center:

Primary Outcome Measures:
  • Cognitive performance [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Brain MR Spectroscopy [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Brain Diffusion Tensor Imaging [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Health-related Quality of Life [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: April 2011
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01556646

Contacts
Contact: Jasmohan S Bajaj, MD 804 675 5802 jsbajaj@vcu.edu

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

No publications provided

Responsible Party: Jasmohan Bajaj, Associate Professor of Medicine, Hunter Holmes Mcguire Veteran Affairs Medical Center
ClinicalTrials.gov Identifier: NCT01556646     History of Changes
Other Study ID Numbers: Bajaj 01720
Study First Received: March 15, 2012
Last Updated: December 10, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Hunter Holmes Mcguire Veteran Affairs Medical Center:
Cirrhosis
Hepatic Encephalopathy
Hyponatremia
 Brain MRI
Health-related quality of life
cognitive function

Additional relevant MeSH terms:
Hyponatremia
Hepatic Encephalopathy
Liver Cirrhosis
Fibrosis
Brain Damage, Chronic
Delirium
Encephalitis
Neurotoxicity Syndromes
Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
 Nervous System Diseases
Metabolic Diseases
Water-Electrolyte Imbalance
Pathologic Processes
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Central Nervous System Viral Diseases
Virus Diseases
Central Nervous System Infections
Poisoning
Substance-Related Disorders

ClinicalTrials.gov processed this record on May 16, 2013