Rifamycin in Minimal Hepatic Encephalopathy

NCT04082780 | Completed Phase 2 FDA Drug

• 1 other identifier: BAJAJ0025
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized double-blind placebo-controlled trial of MHE in patients with cirrhosis using rifamycin SV-MMX 600mg BID vs placebo for 30 days with PK, safety, microbiota, brain function and brain MRI endpoints.

Conditions

Hepatic Encephalopathy; Cirrhosis, Liver

Keywords

brain MRI; cognitive testing; microbiota; metabolomics; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Cirrhosis Dysbiosis Ratio of stool microbiota

  Comparing this ratio in rifamycin compared to placebo groups (Lachnospiraceae + Ruminococcaceae + Clostridium Cluster XIV + Veillonellaceae / Enterobacteriaceae + Bacteroidaceae)

  30 days

Secondary Outcomes (19)

• Psychometric hepatic encephalopathy score (PHES) composite score ranges from -15 to +5

  30 days

• EncephalApp Stroop OffTime+OnTime is the total time taken to complete 5 runs in Off and 5 runs in On state.

  30 days

• Sickness Impact Profile total score is the total score determined after all 12 domains are scored

  30 days

• Sickness Impact Profile psychosocial score is the score of the psychosocial part of the SIP

  30 days

• Sickness Impact Profile physical score is the score of the physical part of the SIP

  30 days

Other Outcomes (3)

• Handgrip strength

  30 days

• Body Muscle composition

  30 days

• Brain MR Spectroscopy in Anterior cingulate cortex, posterior gray matter, and right parietal white matter in a subset

  30 days

Study Arms (2)

Rifamycin

EXPERIMENTAL

Rifamycin-SV MMX 600 mg PO two times a day (1200 mg) for 30 days

Drug: Rifamycin SV MMX

Placebo

PLACEBO COMPARATOR

Placebo PO two times a day for 30 days

Other: Placebo

Interventions

Rifamycin SV MMX DRUG

Intervention arm

Also known as: Aemcolo

Rifamycin

Placebo OTHER

Placebo arm

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years
• Cirrhosis defined by any one of the following
• Cirrhosis on liver biopsy or transient elastography
• Nodular liver on imaging
• Endoscopic or radiological evidence of varices in a patient with chronic liver disease
• Platelet count \<150,000/mm3 and AST/ALT ratio \>1 in a patient with chronic liver disease
• Women of childbearing age will need to be on accepted birth control for 10 days prior to entering study and 30 days after the end of the last dose of the study drug.
• Cognitive impairment on PHES aggregate score \[more than or greater than\] -4SD or EncephalApp Stroop - based on norms published in Allampati et al located at the website www.encephalapp.com17 (This is the accepted diagnosis of minimal HE.)
• Willing and able to participate, provide samples and complete follow-up

You may not qualify if:

• Unclear diagnosis of cirrhosis (does not meet the criteria outlined above)
• Child score \>8
• Unable to consent, follow for the study duration
• Normal performance on PHES
• Mini-mental status exam\<2518
• Recent alcohol abuse (within 3 months)
• Recent illicit drug abuse (within 3 months) except marijuana
• Current use of psychoactive drugs apart from long-standing opioids or stable anti-depressant use.
• Prior overt HE episodes defined as West-Haven Criteria grade 2 or higher in the past that required hospitalization or initiation of lactulose or rifaximin therapy
• Currently on lactulose or rifaximin
• Current or recent invasive bacterial or fungal infections (\<1 month)
• Allergic reactions to rifamycin, rifampin or rifaximin
• MELD \>20
• TIPS placement
• Serum sodium\<125

Sponsors & Collaborators

• Hunter Holmes Mcguire Veteran Affairs Medical Center: lead

Study Sites (1)

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

MeSH Terms

Conditions

Hepatic Encephalopathy; Liver Cirrhosis

Interventions

rifamycin SV

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• JASMOHAN BAJAJ

  Hunter Holmes McGuire Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients will be randomized 1:1 into receiving rifamycin or placebo by a random number generator created by Cosmo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2019
• First Posted: September 9, 2019
• Study Start: September 1, 2019
• Primary Completion: April 28, 2023
• Study Completion: April 28, 2023
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)