A Study of Controlled Lactulose Withdrawal

Sponsor

Hunter Holmes Mcguire Veteran Affairs Medical Center (U.S. Fed)

Overall Status

Completed

CT.gov ID

NCT00914056

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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	N/A

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 We hypothesize that a majority of these patients can be withdrawn from daily lactulose therapy without deterioration of cognitive function, and that lactulose withdrawal will improve symptoms and quality of life for these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

Study Type:

Interventional

Actual Enrollment :

7 participants

Allocation:

N/A

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 :

Sep 1, 2008

Actual Primary Completion Date :

May 1, 2009

Actual Study Completion Date :

May 1, 2012

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Psychometric function and relapse into clinical HE [30 days]

Secondary Outcome Measures

MR Spectroscopy [30 days]
Pro-inflammatory cytokines [30 days]
Stool bacterial DNA analysis [30 days]
Urine and blood for metabolomics [30 days]
Quality of life [30 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia	United States	23249

Sponsors and Collaborators

Hunter Holmes Mcguire Veteran Affairs Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jasmohan Bajaj, Associate Professor of Medicine, Hunter Holmes Mcguire Veteran Affairs Medical Center

ClinicalTrials.gov Identifier:

NCT00914056

Other Study ID Numbers:

Bajaj 006

First Posted:

Jun 4, 2009

Last Update Posted:

Mar 20, 2013

Last Verified:

Mar 1, 2013

Additional relevant MeSH terms:

Hepatic Encephalopathy

Brain Diseases

Lactulose

Study Results

No Results Posted as of Mar 20, 2013