The Role of Bacterial Overgrowth and Delayed Intestinal Transit in Hepatic Encephalopathy.

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by New York University School of Medicine
Sponsor:
Collaborator:
Salix Pharmaceuticals
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT01846806
First received: May 1, 2013
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

This is a prospective study designed to examine the role of bacterial overgrowth and delayed intestinal transit and the effect of Rifaximin with hepatic encephalopathy (HE). This study is divided into Phase A and Phase B. The purpose of Phase A is to test patients with cirrhosis to determine if they have bacterial overgrowth which may lead to slow intestinal transit and hepatic encephalopathy. The purpose of Phase B is to investigate whether the improvement found in patients with hepatic encephalopathy taking Rifaximin is also related to decreased bacterial overgrowth. The target population is patients with chronic liver cirrhosis with or without symptoms of HE. Many patients may present with advanced cirrhosis and may be on the liver transplant list.

During Phase A, 20 patients will be asked to sign the informed consent form and will be assigned a subject number. They will be asked to provide demographic information, medical history, history of hospitalizations for HE, and HE medication use. They will undergo a complete physical examination, urine pregnancy test (women of childbearing potential), 12-lead EKG, grading of ascites, modified Child Pugh Score, MELD Score. They will also complete the following neuropsychological questionnaires: NCT, D-KEFS Trail Making Test, California Verbal Learning Test, WAIS-III Digit Symbol-Coding and Block Design, D-KEFS Stroop Color-Word Test, Evaluation of Constructional Apraxia, , and asterixis. During the evaluatin visit (a minimum of 3 days after the Screening Visit) the following procedures will be performed: lab tests (chemistry and hematology panels). They will also complete the following questionnaires: Liver Disease Quality of Life Questionnaire, Fisk Fatigue Impact Score, Flatulence Survey, Epworth Sleepiness Scale. Finally, they will undergo a Lactulose Hydrogen Breath Test: This test is designed to evaluate both intestinal transit and bacterial overgrowth.

Participants in Phase B will be administered of 550 mg of Rifaximin two times a day for 14 days. Patients will be scheduled to come in on day 14 of the active study period. The follow up visit is day 28, where some of the tests described above will be repeated. During Phase B, patients will be asked to undergo a complete physical examination, a Neurological Examination [including calculation of modified Child Pugh and MELD Score NCT, and Trail Making Test], evaluation of constructional apraxia and asterixis. In addition, the researchers will make sure the patient meets eligibility criteria for participation in open label trial of Rifaximin. They will be administered the first dose study drug (Rifaximin) by study coordinator or investigator and they will be dispensed the study drug needed for the remainder of the trial and a diary for them to record daily flatulence. A urine pregnancy test will be performed within 48 hours of first study dose (for women of childbearing potential). During Day 14 and Day 28 visits, patients will have 1 tablespoon of blood drawn for measurement of the ammonia level and to monitor for potential blood clots. They will complete the NCT, Trails Test, Digit Symbol-Coding, Block Design, and Stroop Tests. They will also complete the Liver Disease Quality of Life Questionnaire, Fisk Fatigue Impact Score, Flatulence Survey (A diary will be provided to the patient with instructions on how to record flatulence experiences on a daily basis), and the Epworth Sleepiness Scale questionnaires. In addition, on Day 14, they will undergo another Lactulose Hydrogen Breath Test.

Subjects' mental capacity will be assessed at each visit via interview, brief mental status, questionnaires and psychometric evaluation. Any subject who appears to have lost capacity to continue participation, as evidenced by HE grade 2 or higher, a lack of attentiveness, concentration, or understanding of evaluation, will be discontinued from the study. Female subjects of childbearing potential will be asked to comply with the use of contraception during the Phase B study period as well as throughout the time they remain on study drug.

Following completion of the study, patients will be categorized by the degree of HE. To determine whether impaired intestinal transit and bacterial overgrowth are associated with severity of HE, multivariate analysis will be performed to determine whether the independent factors of liver disease severity, intestinal transit, and bacterial overgrowth are significant predictors of the presence and severity of HE. Also, to determine whether treatment with Rifaximin improves bacterial overgrowth, ammonia levels, and HE, changes in Breath Test analysis be correlated will be correlated with changes in ammonia levels and HE.


Condition Intervention
Hepatic Encephalopathy
Drug: Rifaximin

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Role of Bacterial Overgrowth and Delayed Intestinal Transit in Hepatic Encephalopathy. Phase A: Breath Testing and Colonic Transit in Hepatic Encephalopathy. Phase B: The Effect of Rifaximin on Bacterial Overgrowth and Severity of Hepatic Encephalopathy in Patients With Severe Hepatic Encephalopathy

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Laboratory results [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
    Results will be evaluated for the following lab tests: blood chemistry (including ammonia and other potential toxins) and hematology panels

  • Lactulose Hydrogen Breath Test [ Time Frame: Day 3 and Day 14 ] [ Designated as safety issue: No ]
    This test is designed to evaluate both intestinal transit and bacterial overgrowth. Subjects will be asked to breathe into a collection bag, drink 10g of lactulose that has been mixed with 8 oz of water, breathe again into the collection bag after waiting 20 minutes and then again every 10 minutes for a total of 2 hours.

  • Quality of Life [ Time Frame: Day 3, Day 14, and Day 28 ] [ Designated as safety issue: No ]
    Participants will be asked to rate levels of depression, fatigue, and sleepiness, as well as decreases or increases in their quality of life.


Estimated Enrollment: 30
Study Start Date: September 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rifaximin
Participants in Phase B will be administered 550 mg of Rifaximin two times a day for 14 days.
Drug: Rifaximin
Participants in Phase B will be administered 550 mg of Rifaximin two times a day for 14 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ambulatory patients with HCV cirrhosis will be screened for participation in the study
  • Ability to complete Number Connection Test
  • Creatinine <1.5mg/dL
  • Able to provide informed consent
  • Patients determined to possibly meet the West Haven criteria grade 0 or 1 for HE

Exclusion Criteria:

  • Active interferon therapy
  • History of alcohol abuse within six months
  • Active gastrointestinal bleeding
  • Use of agents that alter intestinal motility, e.g., methadone, cholestyramine, Tricyclic antidepressants, etc.
  • Use of Neomycin or other antibiotics within the past 2 weeks
  • Pregnancy
  • Unable to provide informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01846806

Contacts
Contact: Samuel Sigal, M 212-263-3643 samuel.sigal@nyumc.org

Locations
United States, New York
NYU Medical Center Recruiting
New York, New York, United States, 10016
Contact: Samuel Sigal, MD    212-263-3643    samuel.sigal@nyumc.org   
Principal Investigator: Samuel Sigal, MD         
Sponsors and Collaborators
New York University School of Medicine
Salix Pharmaceuticals
  More Information

No publications provided

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01846806     History of Changes
Other Study ID Numbers: 10-00570
Study First Received: May 1, 2013
Last Updated: November 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by New York University School of Medicine:
Hepatic Encephalopathy

Additional relevant MeSH terms:
Hepatic Encephalopathy
Brain Damage, Chronic
Delirium
Encephalitis
Neurotoxicity Syndromes
Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolic Diseases
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Central Nervous System Viral Diseases
Virus Diseases
Central Nervous System Infections
Poisoning
Substance-Related Disorders
Rifaximin
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 29, 2014