A Study of Controlled Lactulose Withdrawal

March 19, 2013 updated by: Jasmohan Bajaj, Hunter Holmes Mcguire Veteran Affairs Medical Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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 We hypothesize that a majority of these patients can be withdrawn from daily lactulose therapy without deterioration of cognitive function, and that lactulose withdrawal will improve symptoms and quality of life for these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.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Virginia
      • Richmond, Virginia, United States, 23249
        • Hunter Holmes McGuire VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Lactulose withdrawal
Patients who were started on lactulose as a result of a precipitated HE episode underwent analysis while they were on lactulose; after this they underwent a controlled lactulose withdrawal with 3 visits post-withdrawal at 2 days, 14 days and 30 days after lactulose withdrawal
Drug: lactulose
withdrawal of lactulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Psychometric function and relapse into clinical HE
Time Frame: 30 days
30 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Quality of life
Time Frame: 30 days
30 days
MR Spectroscopy
Time Frame: 30 days
30 days
Pro-inflammatory cytokines
Time Frame: 30 days
30 days
Stool bacterial DNA analysis
Time Frame: 30 days
30 days
Urine and blood for metabolomics
Time Frame: 30 days
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hunter Holmes Mcguire Veteran Affairs Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (ACTUAL)

May 1, 2009

Study Completion (ACTUAL)

May 1, 2012

Study Registration Dates

First Submitted

June 3, 2009

First Submitted That Met QC Criteria

June 3, 2009

First Posted (ESTIMATE)

June 4, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

March 20, 2013

Last Update Submitted That Met QC Criteria

March 19, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Bajaj 006

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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