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Effect of Tolvaptan on Cognitive Function in Cirrhosis

Primary Purpose

Cirrhosis, Hepatic Encephalopathy, Hyponatremia

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Tolvaptan
Sponsored by
Hunter Holmes Mcguire Veteran Affairs Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cirrhosis focused on measuring Cirrhosis, Hepatic Encephalopathy, Hyponatremia, Brain MRI, Health-related quality of life, cognitive function

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Hunter Holmes McGuire VA Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tolvaptan

Arm Description

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

Outcomes

Primary Outcome Measures

Cognitive performance

Secondary Outcome Measures

Brain MR Spectroscopy
Brain Diffusion Tensor Imaging
Health-related Quality of Life

Full Information

First Posted
March 15, 2012
Last Updated
February 6, 2014
Sponsor
Hunter Holmes Mcguire Veteran Affairs Medical Center
Collaborators
Otsuka America Pharmaceutical
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1. Study Identification

Unique Protocol Identification Number
NCT01556646
Brief Title
Effect of Tolvaptan on Cognitive Function in Cirrhosis
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 Type
Interventional

2. Study Status

Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hunter Holmes Mcguire Veteran Affairs Medical Center
Collaborators
Otsuka America Pharmaceutical

4. Oversight

Data Monitoring Committee
No

5. Study Description

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 battery of eight cognitive tests Health related quality of life 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cirrhosis, Hepatic Encephalopathy, Hyponatremia
Keywords
Cirrhosis, Hepatic Encephalopathy, Hyponatremia, Brain MRI, Health-related quality of life, cognitive function

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tolvaptan
Arm Type
Experimental
Arm Description
Open label study of tolvaptan. First 3 days as an inpatient then outpatient for the remainder of the study
Intervention Type
Drug
Intervention Name(s)
Tolvaptan
Other Intervention Name(s)
Samsca
Intervention Description
15 to 30mg qd titrated to sodium concentration
Primary Outcome Measure Information:
Title
Cognitive performance
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Brain MR Spectroscopy
Time Frame
14 days
Title
Brain Diffusion Tensor Imaging
Time Frame
14 days
Title
Health-related Quality of Life
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jasmohan S Bajaj, MD
Organizational Affiliation
Hunter Holmes McGuire VA Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hunter Holmes McGuire VA Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States

12. IPD Sharing Statement

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Effect of Tolvaptan on Cognitive Function in Cirrhosis

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