Clinical trial NCT00914056: A Study of Controlled Lactulose Withdrawal
Official title: Is Continuous Lactulose Therapy Necessary for Patients With Hepatic Encephalopathy? A Prospective Study of Controlled Lactulose Withdrawal
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatic Encephalopathy
Lead sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center
Sponsor class: FED
First posted: 2009-06-04
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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 We hypothesize that a majority of these patients can be withdrawn from daily lactulose therapy without deterioration of cognitive function, and that lactulose withdrawal will improve symptoms and quality of life for these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

Primary outcomes:
measure: Psychometric function and relapse into clinical HE
timeFrame: 30 days
Secondary outcomes:
measure: MR Spectroscopy
timeFrame: 30 days
measure: Pro-inflammatory cytokines
timeFrame: 30 days
measure: Stool bacterial DNA analysis
timeFrame: 30 days
measure: Urine and blood for metabolomics
timeFrame: 30 days
measure: Quality of life
timeFrame: 30 days
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center
state: Virginia
Study officials:
References:
citation: Bajaj JS, Gillevet PM, Patel NR, Ahluwalia V, Ridlon JM, Kettenmann B, Schubert CM, Sikaroodi M, Heuman DM, Crossey MM, Bell DE, Hylemon PB, Fatouros PP, Taylor-Robinson SD. A longitudinal systems biology analysis of lactulose withdrawal in hepatic encephalopathy. Metab Brain Dis. 2012 Jun;27(2):205-15. doi: 10.1007/s11011-012-9303-0. Epub 2012 Apr 12.
citation: Bajaj JS, Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S, Sikaroodi M, Gillevet PM. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol. 2012 Jan 1;302(1):G168-75. doi: 10.1152/ajpgi.00190.2011. Epub 2011 Sep 22.