Hepatic EncephalopathyPhase 2NCT04155099
Investigational Microbiota Restoration Therapeutic for Hepatic Encephalopathy
A Phase 2 study testing RBX7455 in people with Hepatic Encephalopathy and Cirrhosis, Liver, run by Ochsner Health System at 1 site in United States.
Trial summary
Individuals with cirrhosis are likely to develop overt hepatic encephalopathy for which diagnostic modalities and treatment options are limited. The purpose of this study is to determine if individuals with cirrhosis who experience hepatic encephalopathy would benefit from investigational microbiota restoration… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatic Encephalopathy, Cirrhosis, Liver
- What is being tested?
- RBX7455
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2021to 30 Jul 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals who are male or female and are between the ages of 18 and 70 years.
- Individuals with a current diagnosis of liver cirrhosis as evidenced by one or more of the following:
- Liver Biopsy
- OR a clinical suspicion of cirrhosis based on the presence of one or more of the following criteria:
- Radiologic evidence of varices, cirrhosis or portal hypertension
- Laboratory evidence of platelet count <100,000 or AST/ALT ratio >1
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- Endoscopic evidence of varices or portal gastropathy
- Elastography (i.e. Fibroscan)
- Individuals must have at least one previously documented episode of HE.
- Individuals must be able to read and write in the English language.
- Individuals must be able and willing to utilize the electronic device necessary to measure cognitive function without assistance from outside individuals once the training phase has been completed.
- Individuals must be able to provide valid informed consent prior to any study related procedures.
Who cannot join
- Individuals who are color-blind.
- Individuals actively using psychotropic substances including alcohol.
- Individuals who are pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. Study individuals are expected to attest to this fact during their participation time. Females who are not surgically sterile or having undergone greater than one year of menopause will receive urine pregnancy tests at screening and initial drug dosing.
- Presence of TIPS (transjugular intrahepatic portosystemic shunt).
- Individuals with an active bacterial infection and are taking antibiotics for those infections at time of consent.
- Individuals with ANC <800 (neutropenia).
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- Individuals with MELD >17.
- Individuals with platelet count <35,000/mm3.
- Individuals who are immunocompromised due any of the following reasons:
- HIV infection (CD4 count <200/mm3) or AIDS diagnosis
- Inherited/primary immunodeficiency disorders
- Treatment with any anti-neoplastic agent within the last 3 months (excluding locoregional therapy for hepatocellular carcinoma)
- Treatment with any immunosuppressant medications [including but not limited to monoclonal antibodies to B cells or T cells, anti-TNF agents, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine), calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil] within the last 3 months
- Individuals who have previously undergone FMT.
- Individuals with a history of colorectal cancer (all stages).
- Individuals with a history of chronic intrinsic GI diseases such as inflammatory bowel disease (ulcerative colitis, Crohn's disease or microscopic colitis), eosinophilic gastroenteritis, celiac disease or irritable bowel syndrome as determined by Rome III criteria.
- Individuals with a history of colectomy, major gastro-intestinal surgery, or intra-abdominal surgery.
- Individuals with a history of Clostridium difficile infection six months prior to study enrollment.
- Individuals with a history of chronic diarrhea.
- Individuals currently participating in a research trial that involves drug or device intervention.
- Individuals who are unable to fulfill all study criteria.
- Individuals that the PI determines are not capable of participating in the research study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessment of Cognitive Ability and the Intestinal Microbiome in Individuals With Liver Disease Before and After Investigational Microbiota Restoration Therapeutic
Individuals with cirrhosis are likely to develop overt hepatic encephalopathy for which diagnostic modalities and treatment options are limited. The purpose of this study is to determine if individuals with cirrhosis who experience hepatic encephalopathy would benefit from investigational microbiota restoration therapy due to their inherent cognitive alterations. Analysis for a correlation between changes in microbiome composition and specific blood biomarkers could allow for earlier diagnosis of HE which could then be treated earlier and with novel treatments.
Read the detailed description
The investigators hypothesize that changes in an individual's cognition due to HE-related liver cirrhosis can be stabilized and/or improved through investigational microbiota restoration therapeutic treatment. The main objective of this study is to determine if investigational microbiota restoration therapeutic treatment alters the cognitive function in individuals with cirrhosis who have been previously diagnosed with overt hepatic encephalopathy (HE). Once individuals have one HE episode, they are more likely to experience additional episodes, even after complying with standard of care. The number of HE episodes each study group experiences during the post-treatment follow-up will be compared among treatment groups. It is also anticipated that cognitive improvement will correlate with specific changes in the intestinal microbiota composition of these individuals likely shifting their microbiome away from baseline samples and becoming more like donor samples. Novel blood biomarkers potentially related to episodes of HE will be assessed in individuals before and after treatment.
- Conditions
- Hepatic Encephalopathy, Cirrhosis, Liver
- Being tested
- RBX7455, Placebo
- Keywords
- encephalopathy
- Medical subject headings
- Hepatic Encephalopathy, Liver Cirrhosis, Brain Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RBX7455Biological
Also called Microbiota Restoration Therapy
RBX7455 is a preparation of live intestinal microorganisms (active drug) purified from stool donations obtained from healthy, screened donors, mixed with preservative, lyophilized, and put into capsules. The capsules are taken orally (i.e., by mouth). After ingestion, these freeze-dried microorganisms can reconstitute and proliferate in the gut.
PlaceboBiological
Capsule with cellulose filler
| Study group | Role | What they receive |
|---|---|---|
| High dose | Experimental | Capsules of active drug will be supplied in 8-capsule blister packets to be taken twice per week for four weeks. Blood and stool samples and cognitive assessments will be collected before treatment and at 1, 3, 6, and 12 months after treatment. Receives: Biological: RBX7455 |
| Low dose | Experimental | Capsules of active drug will be supplied in 4-capsule blister packets to be taken twice per week for four weeks. Blood and stool samples and cognitive assessments will be collected before treatment and at 1, 3, 6, and 12 months after treatment. Receives: Biological: RBX7455 |
| pill quantity-matched Placebo | Placebo comparator | Capsules of inactive compound will be supplied in 8- or 4-capsule blister packets to be taken twice per week for four weeks. Blood and stool samples and cognitive assessments will be collected before treatment and at 1, 3, 6, and 12 months after treatment. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cognitive function at 1 month post-FMT as measured by change in response times on EncephalApp (Stroop test)
Determine whether microbiota restoration therapy improves cognition 1 month after treatment by measuring differences in time scores from EncephalApp. The app times participants in seconds (s) in variations of the Stroop Test. The average (s) across all trials will be reported as well as the difference in (s) between (trial 1)-(trial 5). Longer completion times indicate greater cognitive impairment, while a decrease in completion time from trial 1 to trial 5 indicates learning (cognitive improvement).
The scale for this measure is theoretically 0s-500s.
Measured: 1 month
Secondary outcomes (3)
Number of HE episodes
Once individuals have one HE episode, they are more likely to experience additional ones, even after complying with standard of care. The number of HE episodes each study group experiences during the post-treatment follow-up will be compared among treatment groups.
Measured: 1 month to 12 months
Engraftment of FMT as assessed by change in type and abundance of gut microbiota following shotgun sequencing
It is anticipated that with treatment, changes in the intestinal microbiota composition of these individuals will likely shift their microbiome to contain different species. Microbiome analyses will measure, at the family and genus level, which bacteria are present and their relative abundance. Samples from the same individual at different time points will be compared as well as differences between treatment groups at each time point.
Measured: 1 month to 12 months
Change in cognitive function at 3, 6 and 12 months post-FMT as measured by change in response times on EncephalApp (Stroop test)
Determine whether microbiota restoration therapy improves cognition 3, 6, and 12 months after treatment by measuring differences in time scores from EncephalApp. The app times participants in seconds (s) in variations of the Stroop Test. The average (s) across all trials will be reported as well as the difference in (s) between (trial 1)-(trial 5). Longer completion times indicate greater cognitive impairment, while a decrease in completion time from trial 1 to trial 5 indicates learning (cognitive improvement).
Measured: 3 to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2019
- Study start1 Mar 2021
- Primary completion30 Jul 2023
- Study completion30 Jul 2023
Why it stopped: Unable to recruit participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Study individuals will be placed into one of four study treatment groups: High dose investigational microbiota restoration therapeutic RBX7455 group, Low dose investigational microbiota restoration therapeutic RBX7455 group, or a pill quantity-matched Placebo group. Individuals will be randomized in a 1:1:1/2:1/2 manner. It is anticipated of the 75 potentially enrolled individuals, 50 will receive active treatment (high or low dose investigational microbiota restoration therapeutic) and 25 will receive placebo.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ochsner Health System
- Sponsor type
- University, hospital or other
- Collaborators
- Rebiotix Inc.
- Responsible party
- Sponsor
- Investigators
- Julia Garcia-Diaz, MD, Principal investigator, Ochsner Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04155099
- Sponsor's protocol ID
- 2019.193
- Status last verified
- Sep 2023
- First submitted
- 21 Aug 2019
- Last updated
- 3 Oct 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Cognitive Ability and the Intestinal Microbiome in Individuals With Liver Disease Before and After Investigational Microbiota Restoration Therapeutic
- ClinicalTrials.gov ID
- NCT04155099
- Acronym / sponsor ID
- 2019.193
- Conditions
- Hepatic Encephalopathy, Cirrhosis, Liver
- Keywords
- encephalopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to recruit participants
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Ochsner Health SystemUniversity, hospital or other
- Collaborators
- Rebiotix Inc.
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 30 Jul 2023 (actual)
- Study completion
- 30 Jul 2023 (actual)
- First posted
- 7 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Individuals with cirrhosis are likely to develop overt hepatic encephalopathy for which diagnostic modalities and treatment options are limited. The purpose of this study is to determine if individuals with cirrhosis who experience hepatic encephalopathy would benefit from investigational microbiota restoration therapy due to their inherent cognitive alterations. Analysis for a correlation between changes in microbiome composition and specific blood biomarkers could allow for earlier diagnosis of HE which could then be treated earlier and with novel treatments.
Detailed description
The investigators hypothesize that changes in an individual's cognition due to HE-related liver cirrhosis can be stabilized and/or improved through investigational microbiota restoration therapeutic treatment. The main objective of this study is to determine if investigational microbiota restoration therapeutic treatment alters the cognitive function in individuals with cirrhosis who have been previously diagnosed with overt hepatic encephalopathy (HE). Once individuals have one HE episode, they are more likely to experience additional episodes, even after complying with standard of care. The number of HE episodes each study group experiences during the post-treatment follow-up will be compared among treatment groups. It is also anticipated that cognitive improvement will correlate with specific changes in the intestinal microbiota composition of these individuals likely shifting their microbiome away from baseline samples and becoming more like donor samples. Novel blood biomarkers potentially related to episodes of HE will be assessed in individuals before and after treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- Study individuals will be placed into one of four study treatment groups: High dose investigational microbiota restoration therapeutic RBX7455 group, Low dose investigational microbiota restoration therapeutic RBX7455 group, or a pill quantity-matched Placebo group. Individuals will be randomized in a 1:1:1/2:1/2 manner. It is anticipated of the 75 potentially enrolled individuals, 50 will receive active treatment (high or low dose investigational microbiota restoration therapeutic) and 25 will receive placebo.
| Arm | Type | Receives |
|---|---|---|
| High dose | Experimental | Biological: RBX7455Capsules of active drug will be supplied in 8-capsule blister packets to be taken twice per week for four weeks. Blood and stool samples and cognitive assessments will be collected before treatment and at 1, 3, 6, and 12 months after treatment. |
| Low dose | Experimental | Biological: RBX7455Capsules of active drug will be supplied in 4-capsule blister packets to be taken twice per week for four weeks. Blood and stool samples and cognitive assessments will be collected before treatment and at 1, 3, 6, and 12 months after treatment. |
| pill quantity-matched Placebo | Placebo comparator | Biological: PlaceboCapsules of inactive compound will be supplied in 8- or 4-capsule blister packets to be taken twice per week for four weeks. Blood and stool samples and cognitive assessments will be collected before treatment and at 1, 3, 6, and 12 months after treatment. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Individuals who are male or female and are between the ages of 18 and 70 years.
- Individuals with a current diagnosis of liver cirrhosis as evidenced by one or more of the following:
- OR a clinical suspicion of cirrhosis based on the presence of one or more of the following criteria:
- Individuals must have at least one previously documented episode of HE.
- Individuals must be able to read and write in the English language.
Key exclusion criteria (22 listed)
- Individuals who are color-blind.
- Individuals actively using psychotropic substances including alcohol.
- Individuals who are pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. Study individuals are expected to attest to this fact during their participation time. Females who are not surgically sterile or having undergone greater than one year of menopause will receive urine pregnancy tests at screening and initial drug dosing.
- Presence of TIPS (transjugular intrahepatic portosystemic shunt).
- Individuals with an active bacterial infection and are taking antibiotics for those infections at time of consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RBX7455Also: Microbiota Restoration TherapyRBX7455 is a preparation of live intestinal microorganisms (active drug) purified from stool donations obtained from healthy, screened donors, mixed with preservative, lyophilized, and put into capsules. The capsules are taken orally (i.e., by mouth). After ingestion, these freeze-dried microorganisms can reconstitute and proliferate in the gut. | Biological | High dose, Low dose |
| PlaceboCapsule with cellulose filler | Biological | pill quantity-matched Placebo |
Primary outcome
Change in cognitive function at 1 month post-FMT as measured by change in response times on EncephalApp (Stroop test)
Time frame: 1 month
Determine whether microbiota restoration therapy improves cognition 1 month after treatment by measuring differences in time scores from EncephalApp. The app times participants in seconds (s) in variations of the Stroop Test. The average (s) across all trials will be reported as well as the difference in (s) between (trial 1)-(trial 5). Longer completion times indicate greater cognitive impairment, while a decrease in completion time from trial 1 to trial 5 indicates learning (cognitive improvement). The scale for this measure is theoretically 0s-500s.
3 secondary outcomes
Number of HE episodes
Time frame: 1 month to 12 months
Engraftment of FMT as assessed by change in type and abundance of gut microbiota following shotgun sequencing
Time frame: 1 month to 12 months
Change in cognitive function at 3, 6 and 12 months post-FMT as measured by change in response times on EncephalApp (Stroop test)
Time frame: 3 to 12 months
Results and safety
The study was stopped early (reason given: Unable to recruit participants). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julia Garcia-Diaz, MD principal investigator
Ochsner Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RBX7455 in people with Hepatic Encephalopathy and Cirrhosis, Liver, run by Ochsner Health System at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Unable to recruit participants). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cognitive function at 1 month post-FMT as measured by change in response times on EncephalApp (Stroop test) (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2023.