A Study of Controlled Lactulose Withdrawal

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00914056
Recruitment Status : Completed
First Posted : June 4, 2009
Last Update Posted : March 20, 2013
Information provided by (Responsible Party):
Jasmohan Bajaj, Hunter Holmes Mcguire Veteran Affairs Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Hepatic Encephalopathy Drug: lactulose Not Applicable

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 We hypothesize that a majority of these patients can be withdrawn from daily lactulose therapy without deterioration of cognitive function, and that lactulose withdrawal will improve symptoms and quality of life for these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  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Is Continuous Lactulose Therapy Necessary for Patients With Hepatic Encephalopathy? A Prospective Study of Controlled Lactulose Withdrawal
Study Start Date : September 2008
Actual Primary Completion Date : May 2009
Actual Study Completion Date : May 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Lactulose
U.S. FDA Resources

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

Primary Outcome Measures :
  1. Psychometric function and relapse into clinical HE [ Time Frame: 30 days ]

Secondary Outcome Measures :
  1. MR Spectroscopy [ Time Frame: 30 days ]
  2. Pro-inflammatory cytokines [ Time Frame: 30 days ]
  3. Stool bacterial DNA analysis [ Time Frame: 30 days ]
  4. Urine and blood for metabolomics [ Time Frame: 30 days ]
  5. Quality of life [ Time Frame: 30 days ]

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00914056

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

Publications of Results:
Responsible Party: Jasmohan Bajaj, Associate Professor of Medicine, Hunter Holmes Mcguire Veteran Affairs Medical Center Identifier: NCT00914056     History of Changes
Other Study ID Numbers: Bajaj 006
First Posted: June 4, 2009    Key Record Dates
Last Update Posted: March 20, 2013
Last Verified: March 2013

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