NCT00914056

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
7

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Sep 2008

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2008

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2009

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

June 3, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 4, 2009

Completed
2.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2012

Completed
Last Updated

March 20, 2013

Status Verified

March 1, 2013

Enrollment Period

8 months

First QC Date

June 3, 2009

Last Update Submit

March 19, 2013

Conditions

Hepatic Encephalopathy

Outcome Measures

Primary Outcomes (1)

  • Psychometric function and relapse into clinical HE

    30 days

Secondary Outcomes (5)

  • 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

Study Arms (1)

Lactulose withdrawal

EXPERIMENTAL

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

Interventions

lactuloseDRUG

withdrawal of lactulose

Lactulose withdrawal

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Related Publications (2)

  • 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.

    PMID: 22527995RESULT

  • 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.

    PMID: 21940902RESULT

MeSH Terms

Conditions

Hepatic Encephalopathy

Interventions

Lactulose

Condition Hierarchy (Ancestors)

Liver FailureHepatic InsufficiencyLiver DiseasesDigestive System DiseasesBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

DisaccharidesOligosaccharidesPolysaccharidesCarbohydratesSugars

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
FED
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Medicine

Study Record Dates

First Submitted

June 3, 2009

First Posted

June 4, 2009

Study Start

September 1, 2008

Primary Completion

May 1, 2009

Study Completion

May 1, 2012

Last Updated

March 20, 2013

Record last verified: 2013-03

Locations

US(1)