Rifaximin for Dementia

(RIDE Trial)

Overseen By Haley Obolewicz, RN

Age: 65+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jasmohan Bajaj

Must not be taking: Antipsychotics, Antibiotics

Disqualifiers: Severe psychopathology, Unstable medical conditions, others

Compensation: Varies

Number of Visits: Unknown

Duration: 10 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new form of the antibiotic rifaximin can positively impact gut microbes in people with dementia. Participants will take either the actual medication or a placebo (a pill with no active medicine) without knowing which one they receive. The goal is to determine if this treatment can benefit those with mild to moderate Alzheimer’s or vascular dementia. Individuals living with these types of dementia, who have a caregiver to assist them, might be suitable for this trial. As a Phase 1, Phase 2 trial, the research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take medications that interact with Rifaximin. If you are on P-glycoprotein (P-gp) inhibitors, you can continue them, but you need to discuss this with the investigator.

Is there any evidence suggesting that Rifaximin SSD is likely to be safe for humans?

Research has shown that Rifaximin SSD is safe and well-tolerated in people with Alzheimer's Disease (AD) and Vascular Dementia (VaD). Studies have found that patients taking this treatment experienced positive changes in inflammation and other body markers, indicating its safety. Rifaximin, the main ingredient, already treats conditions like hepatic encephalopathy and has a good safety record. It does not interact with other medications and is easy to take orally. While direct evidence of its effectiveness in treating dementia is not yet available, its use in other conditions suggests it is generally safe for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for dementia?

Rifaximin SSD is unique because it offers a novel approach to treating dementia by targeting the gut-brain axis, which is different from traditional treatments that primarily focus on neurotransmitter systems in the brain. Unlike standard dementia medications like cholinesterase inhibitors or memantine, rifaximin acts as an antibiotic that may help reduce neuroinflammation and improve cognitive symptoms by altering gut microbiota composition. Researchers are excited about its potential to provide a new, complementary mechanism of action that could enhance or extend the benefits of current therapies.

What evidence suggests that this treatment might be an effective treatment for dementia?

Research suggests that rifaximin, an antibiotic that remains in the gut, might aid people with dementia by altering gut bacteria. Although no direct proof exists yet for its effectiveness in dementia, rifaximin has improved hepatic encephalopathy, a condition that also impacts the brain. By modifying gut bacteria, rifaximin could potentially enhance brain health in dementia patients. Early studies have shown it to be safe and generally well tolerated, with some positive effects on inflammation. This offers hope for its potential to alter the disease's progression. Participants in this trial will receive either Rifaximin SSD 40mg IR BID or a placebo, with the order of administration concealed. ^{1 3 4 5 6}

Who Is on the Research Team?

Jasmohan Bajaj

Principal Investigator

Richmond VA Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals aged 65 or older with mild to moderate Alzheimer's Disease or Vascular Dementia. Participants must be able to consent (or have a legal guardian who can), speak English, and live in the community with a caregiver available.

Inclusion Criteria

Fluency (both participant and caregiver) in written and spoken English to participate in study visits

Able to consent or legal guardian who can consent (with participant assent)

I live at home and have someone who can come with me to study visits.

Exclusion Criteria

I am experiencing diarrhea.

I have not taken antibiotics in the last 6 months.

Severe psychopathology including major depression

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Rifaximin SSD or placebo in a single-blind, placebo-controlled trial to assess changes in gut microbiota and systemic biomarkers

10 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Rifaximin SSD

Trial Overview The study tests Rifaximin SSD, a new non-absorbable antibiotic formulation, against a placebo to see if it positively affects gut microbes in dementia patients.

How Is the Trial Designed?

Group I: Rifaximin SSD 40mg IR BID Experimental Treatment 1 Intervention

Patients will be given placebo and actual drug sequentially with the order hidden

Group II: Placebo Placebo Group 1 Intervention

Patients will be given placebo and actual drug sequentially with the order hidden

Who Is Running the Clinical Trial?

Jasmohan Bajaj

Lead Sponsor

Trials

2

Recruited

40+

Bausch Health Companies, INC.

Collaborator

Trials

2

Recruited

90+

Bausch Health Americas, Inc.

Industry Sponsor

Trials

265

Recruited

82,000+

Dr. Jonathan Sadeh

Bausch Health Americas, Inc.

Chief Medical Officer

MD from Mount Sinai School of Medicine, MSc in Clinical Research from Harvard Medical School

Thomas J. Appio

Bausch Health Americas, Inc.

Chief Executive Officer since 2021

Bachelor's degree in Biology from Rutgers University

Published Research Related to This Trial

Rifaximin is effective in improving symptoms of hepatic encephalopathy, showing superior and faster results compared to traditional treatments like lactulose, and it also reduces hospitalization needs and costs.

The treatment is generally well-tolerated, with mostly minor gastrointestinal side effects, making it a safer option compared to other medications for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin for the treatment of hepatic encephalopathy. Lawrence, KR., Klee, JA.[2022]

Long-term treatment with rifaximin (RFX) significantly reduced blood ammonia levels and improved liver function in patients with hepatic encephalopathy (HE), with a median follow-up of 41.6 weeks.

The recurrence rate of HE was found to be 26.2%, with the presence of ascites at baseline being a significant risk factor for recurrence, highlighting the importance of monitoring this condition in patients undergoing RFX treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effects of long-term rifaximin treatment for Japanese patients with hepatic encephalopathy. Suzuki, H., Sezaki, H., Suzuki, F., et al.[2020]

A survey of 159 physicians revealed that treatment choices for cognitive disorders in dementia patients showed little variation between Alzheimer's type dementia (SDAT) and vascular dementia (VD), indicating that the type of dementia does not significantly influence medication selection.

Commonly prescribed cognition enhancers included piracetam, ginkgo biloba, and nimodipine, with a notable preference for ginkgo biloba among family physicians, highlighting the importance of cost and safety in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribing practice with cognition enhancers in outpatient care: are there differences regarding type of dementia?--Results of a representative survey in lower Saxony, Germany. Stoppe, G., Sandholzer, H., Staedt, J., et al.[2016]

Rifaximin significantly improved blood ammonia levels and the portal systemic encephalopathy index in Japanese patients with hepatic encephalopathy (HE) during a 14-day treatment period, demonstrating its efficacy.

The treatment was well tolerated, with only 13.4% of patients experiencing adverse drug reactions, none of which were severe enough to cause death, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial. Suzuki, K., Endo, R., Takikawa, Y., et al.[2020]

Rifaximin shows better efficacy in treating hepatic encephalopathy (HE) compared to traditional treatments like lactulose and neomycin, based on clinical trials.

Rifaximin has a superior safety and tolerability profile compared to lactulose and possibly neomycin, making it a promising alternative for patients with HE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin for the treatment of hepatic encephalopathy. de Melo, RT., Charneski, L., Hilas, O.[2019]

Rifaximin has been shown to be more effective than lactulose in treating hepatic encephalopathy (HE), with studies indicating it leads to fewer hospitalizations and lower healthcare costs.

The safety profile of rifaximin is favorable, as it is better tolerated compared to other treatments like paromomycin and neomycin, making it a promising option for patients with liver failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin for treatment of hepatic encephalopathy. Maclayton, DO., Eaton-Maxwell, A.[2018]

In a study of 135 elderly patients with Alzheimer's disease, low-dose risperidone (starting at 0.5 mg and increasing to a mean of 1 mg/day) significantly reduced behavioral and psychological symptoms of dementia (BPSD) over 12 weeks, as measured by the Neuropsychiatric Inventory and the BEHAVE-AD scale.

Risperidone was well tolerated, with significant improvements in symptoms like agitation, aggression, and anxiety, indicating its efficacy and safety for managing dementia-related disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with risperidone in the treatment of behavioral and psychological symptoms of dementia. Onor, ML., Saina, M., Trevisiol, M., et al.[2013]

In a study of 625 elderly patients with severe dementia, risperidone significantly reduced psychotic and aggressive symptoms compared to placebo, particularly at doses of 1 mg/day and 2 mg/day.

The 1 mg/day dose of risperidone was found to be effective without significantly increasing the risk of extrapyramidal symptoms, making it a suitable treatment option for managing behavioral symptoms in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. Risperidone Study Group. Katz, IR., Jeste, DV., Mintzer, JE., et al.[2022]

A meta-analysis of 8 randomized controlled trials with 407 patients found that rifaximin is at least as effective as nonabsorbable disaccharides for treating hepatic encephalopathy, with significant improvements in grades of portosystemic encephalopathy.

Rifaximin demonstrated better safety compared to nonabsorbable disaccharides, indicating it may be a preferable treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin versus Nonabsorbable Disaccharides for the Treatment of Hepatic Encephalopathy: A Meta-Analysis. Wu, D., Wu, SM., Lu, J., et al.[2022]

A randomized trial involving 406 patients with mild to moderate Alzheimer's disease found that treatment with doxycycline and rifampin did not improve cognitive function or daily living activities over 12 months.

Both doxycycline and rifampin alone led to a significant decline in cognitive scores compared to placebo, and their combination did not show any beneficial effects, indicating these treatments are not effective for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, blinded, randomized, factorial controlled trial of doxycycline and rifampin for treatment of Alzheimer's disease: the DARAD trial. Molloy, DW., Standish, TI., Zhou, Q., et al.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06718686

Study Details | NCT06718686 | Rifaximin SSD in Dementia ... Rifaximin SSD therapy is safe and well tolerated in patients with AD and VaD with beneficial changes in systemic inflammation and systemic biomarkers of ...

2. withpower.com withpower.com/trial/rifaximin-for-dementia-f144f

Rifaximin for Dementia (RIDE Trial) There is no direct evidence supporting the effectiveness of Rifaximin SSD for dementia, but Rifaximin has been shown to improve hepatic encephalopathy, a ...

3. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/559976

Rifaximin SSD in Dementia Trial Using a new formulation of rifaximin, a non-absorbable antibiotic, to test if it can affect microbes in the gut of patients with dementia ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8804600/

Probing gut‐brain links in Alzheimer's disease with rifaximin We hypothesized that treatment with rifaximin, a minimally absorbed gut‐specific antibiotic, may modify the neurodegenerative process by changing gut flora.

5. patientcareonline.com patientcareonline.com/view/the-liver-meeting-2024-bausch-health-presents-phase-3-study-design-for-investigational-rifaximin-formulation-to-delay-ohe

The Liver Meeting 2024: Bausch Health Presents Phase 3 ... The RED-C program is evaluating the efficacy of a next generation therapeutic, a soluble solid dispersion (SSD) immediate-release rifaximin ...

6. trialx.com trialx.com/clinical-trials/listings/294158/rifaximin-ssd-in-dementia-trial/

Rifaximin SSD in Dementia Trial Hypothesis: Rifaximin SSD therapy is safe and well tolerated in patients with AD and VaD with beneficial changes in systemic inflammation and ...