A Study of Controlled Lactulose Withdrawal

Hepatic Encephalopathy Clinical Trial

Official title:

Is Continuous Lactulose Therapy Necessary for Patients With Hepatic Encephalopathy? A Prospective Study of Controlled Lactulose Withdrawal

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00914056
• Other study ID #: Bajaj 006
• Status: Completed
• Phase: N/A
• First received: June 3, 2009
• Last updated: March 19, 2013
• Start date: September 2008
• Est. completion date: May 2012

Study information

• Verified date: March 2013
• Source: Hunter Holmes Mcguire Veteran Affairs Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

After resolution of the initial episode of hepatic encephalopathy (HE), lactulose is routinely continued indefinitely as maintenance therapy. Although widely used for this indication, lactulose has never been shown in randomized, controlled trials to be effective for preventing exacerbations of HE. Indeed, lactulose was found to be ineffective at preventing HE when administered prophylactically to patients undergoing portosystemic shunt insertion. While some patients may be lactulose dependent following an initial episode of HE, it is likely that most could have their lactulose discontinued with no adverse consequences.

This goal is worth pursuing because lactulose is not innocuous. It has an unpleasant taste, and it routinely produces gastrointestinal symptoms, including bloating, gas and diarrhea. In high doses it can cause incontinence, dehydration and electrolyte derangements. Patients universally dislike taking lactulose and often are noncompliant with treatment. A recent trial showed that patients on lactulose had a substantial risk of hospital admissions due to lactulose-related complications and treatment non-compliance.

Description:

In this pilot study we propose to perform controlled lactulose withdrawal in selected patients with HE whose initial presentation follows a clearly defined, reversible precipitating event or those with stable, chronic HE. We hypothesize that a majority of these patients can be withdrawn from daily lactulose therapy without deterioration of cognitive function, and that lactulose withdrawal will improve symptoms and quality of life for these individuals. We propose to carry out a comprehensive battery of clinical, laboratory, microbiological and psychometric evaluations before and after lactulose withdrawal. We will closely follow changes in cognitive function and re-institute lactulose therapy at the first sign of clinical deterioration. Through multivariate analysis we propose to develop a model to discriminate between treatment dependent and treatment independent patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: May 2012
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Diagnosis of hepatic cirrhosis based on biopsy, clinical and/or radiological findings.

• Stable HE (chronic): On daily lactulose for more than 6 months without hospitalization for HE within 3 months of enrollment.

• Treated with lactulose on a daily basis, with restoration of mental status to baseline.

• Lives with an adult individual who is willing to serve as a full-time caregiver.

• Able and willing to give informed consent.

Exclusion Criteria:

• Use of antibiotics, including rifaximin.

• Patient without an adult caregiver.

• Pre-existing focal neurological deficits, seizures or other indication of structural neurological disorder.

• Actively abusing illicit drugs or alcohol.

Study Design

Endpoint Classification: Bio-equivalence Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Brain Diseases
• Hepatic Encephalopathy

Intervention

Drug:
• lactulose
withdrawal of lactulose

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Hunter Holmes Mcguire Veteran Affairs Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (2)

Bajaj JS, Gillevet PM, Patel NR, Ahluwalia V, Ridlon JM, Kettenmann B, Schubert CM, Sikaroodi M, Heuman DM, Crossey MM, Bell DE, Hylemon PB, Fatouros PP, Taylor-Robinson SD. A longitudinal systems biology analysis of lactulose withdrawal in hepatic enceph — View Citation

Bajaj JS, Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S, Sikaroodi M, Gillevet PM. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol. 2012 Jan 1;302(1):G168-75. doi: 10.1152/ajpgi.00190.201 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Psychometric function and relapse into clinical HE		30 days	Yes
Secondary	MR Spectroscopy		30 days	No
Secondary	Pro-inflammatory cytokines		30 days	No
Secondary	Stool bacterial DNA analysis		30 days	No
Secondary	Urine and blood for metabolomics		30 days	No
Secondary	Quality of life		30 days	No