A Study of Controlled Lactulose Withdrawal

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jasmohan Bajaj, Hunter Holmes Mcguire Veteran Affairs Medical Center
ClinicalTrials.gov Identifier:
NCT00914056
First received: June 3, 2009
Last updated: March 19, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention
Hepatic Encephalopathy
Drug: lactulose

Study Type: Interventional
Study Design: Endpoint Classification: Bio-equivalence Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Is Continuous Lactulose Therapy Necessary for Patients With Hepatic Encephalopathy? A Prospective Study of Controlled Lactulose Withdrawal

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Psychometric function and relapse into clinical HE [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • MR Spectroscopy [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Pro-inflammatory cytokines [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Stool bacterial DNA analysis [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Urine and blood for metabolomics [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Enrollment: 7
Study Start Date: September 2008
Study Completion Date: May 2012
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00914056

Locations
United States, Virginia
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, United States, 23249
Sponsors and Collaborators
Hunter Holmes Mcguire Veteran Affairs Medical Center
  More Information

Publications:
Responsible Party: Jasmohan Bajaj, Associate Professor of Medicine, Hunter Holmes Mcguire Veteran Affairs Medical Center
ClinicalTrials.gov Identifier: NCT00914056     History of Changes
Other Study ID Numbers: Bajaj 006
Study First Received: June 3, 2009
Last Updated: March 19, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Hepatic Encephalopathy
Brain Diseases
Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Brain Diseases, Metabolic
Central Nervous System Diseases
Nervous System Diseases
Metabolic Diseases
Lactulose
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014