Effect of Tolvaptan on Cognitive Function in Cirrhosis

Cirrhosis Clinical Trial

Official title:

Effects of Tolvaptan on Cognitive Function, Brain Metabolism and Quality of Life in Hyponatremic Cirrhotics With Hepatic Encephalopathy: A Prospective Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01556646
• Other study ID #: Bajaj 01720
• Status: Completed
• Phase: Phase 3
• First received: March 15, 2012
• Last updated: February 6, 2014
• Start date: April 2011
• Est. completion date: June 2013

Study information

• Verified date: February 2014
• Source: Hunter Holmes Mcguire Veteran Affairs Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Diseases
• Cirrhosis
• Hepatic Encephalopathy
• Hyponatremia
• Liver Cirrhosis

Intervention

Drug:
• Tolvaptan
15 to 30mg qd titrated to sodium concentration

Locations

Country	Name	City	State
United States	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Hunter Holmes Mcguire Veteran Affairs Medical Center	Otsuka America Pharmaceutical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognitive performance		14 days	No
Secondary	Brain MR Spectroscopy		14 days	No
Secondary	Brain Diffusion Tensor Imaging		14 days	No
Secondary	Health-related Quality of Life		14 days	No