A 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 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|
- Psychometric function and relapse into clinical HE [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
- 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 ]
|Study Start Date:||September 2008|
|Study Completion Date:||May 2012|
|Primary Completion Date:||May 2009 (Final data collection date for primary outcome measure)|
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
withdrawal of lactulose
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.