Rifaximin SSD in Dementia Trial (RIDE)

Rifaximin in Dementia Trial (RIDE): Gut-Brain Modulation With Rifaximin SSD in Dementia

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

Study Overview

• Status: Recruiting
• Conditions: Dementia Associated With Cerebrovascular Disease; Dementia Alzheimer Type
• Intervention / Treatment: Drug: Placebo; Drug: Rifaximin SSD 40 mg IR tablet

Detailed Description

Hypothesis: Rifaximin SSD therapy is safe and well tolerated in patients with AD and VaD with beneficial changes in systemic inflammation and systemic biomarkers of dementia due to improvement in microbiota function compared to placebo-related changes in a single-blind, placebo-controlled Phase 1b/2a trial .

Overall Objective: In a single blind placebo-controlled trial in patients with Alzheimer's or vascular dementia, to determine the effect of rifaximin SSD compared to placebo on gut microbial structure and function, cognitive and daily function, and caregiver burden.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jasmohan S Bajaj, MD; Phone Number: 804-675-5802; Email: jasmohan.bajaj@vcuhealth.org
• Study Contact Backup: Name: Haley Obolewicz, RN; Phone Number: 804-675-5705; Email: haley.obolewicz@va.gov

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Recruiting
      • Richmond VA Medical Center
      • Contact: Haley Obolewicz, RN; Phone Number: 15705 804-675-5000; Email: haley.obolewicz@va.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Probable Alzheimer's Disease (AD) or Vascular Dementia (VaD) mild or moderate based on Clinical Dementia Rating Scale.
• Males and Females Age ≥ 65 years
• Community living with availability of caregiver to accompany participant to study visits and to participate in the study.
• Able to consent or legal guardian who can consent (with participant assent).
• Legally authorized representative (LAR) and caregiver for the study is the same individual.
• Fluency (both participant and caregiver) in written and spoken English to participate in study visits.

Exclusion Criteria:

• Dementia not due to AD or VaD
• Clinically significant agitation or aggression (requiring treatment with antipsychotic medication)
• Delusions and/or hallucinations
• Severe psychopathology including major depression
• Unstable, severe, or poorly controlled medical conditions evident from physical examination or clinical history
• Visual and/or hearing disorder that prevents completion of neuropsychologic evaluations.
• Diarrhea
• Hypersensitivity to rifaximin, components of rifaximin,
• and any rifamycin antimicrobial agent
• Antibiotic use in the prior 6 months
• Taking medications that interact with Rifaximin. P-glycoprotein (P-gp) inhibitor treatment is permitted as long as the use of P-gp inhibitors is discussed with the investigator.
• History of alcohol and/or drug abuse
• Participation in another investigational drug trial in the last 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patients will be given placebo and actual drug sequentially with the order hidden	Drug: Placebo; Placebo drug
Experimental: Rifaximin SSD 40mg IR BID; Patients will be given placebo and actual drug sequentially with the order hidden	Drug: Rifaximin SSD 40 mg IR tablet; Drug therapy vs placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in stool and serum short-chain fatty acid levels	Change in SCFA in stool and serum in rifaximin SSD phase vs placebo phase	10 weeks
Change in bile acids in stool and serum	Change in bile acids in stool and serum in rifaximin SSD phase vs placebo phase	10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systemic inflammatory change	serum lipopolysaccharide-binding protein (LBP), inflammatory cytokines (IL-6, TNF-α, IL-10, IL-1β) in placebo phase vs Rifaximin SSD phase	10 weeks
Stool microbiome composition	16SrRNA microbiome composition and diversity change in placebo vs Rifaximin SSD phase	10 weeks
Change in dementia biomarkers	Plasma concentrations of Aβ42 and Aβ40 to calculate amyloid-β (Aβ)42/40 ratio and plasma concentration of phospho-tau (p-tau)181 in placebo vs Rifaximin SSD phase	10 weeks
MMSE	Change in MMSE between the 2 phases	10 weeks
Cognitive testing using Psychometric Hepatic Encephalopathy Score	Change in PHES in placebo vs rifaximin SSD phase	10 weeks
Clinical Dementia Rating - Sum of Boxes (CDR-SB)	Change in CDR-SB in placebo vs Rifaximin SSD phase	10 weeks
EncephalApp Stroop performance	Change in off time and on time in seconds between placebo and rifaximin SSD phases	10 weeks
Critical flicker fusion analysis	change in threshold to see CFF fusion in rifaximin SSD vs placebo phases	10 weeks
Katz Index of Independence in Activity of Daily Living (ADL)	change in the score above judged by caregivers in placebo vs Rifaximin SSD phase	10 weeks
Lawton-Brody Instrumental Activities of Daily Living (IADL)	Change in instrument score above by caregivers in rifaximin SSD vs placebo phase	10 weeks
Zarit Burden Interview short form	Change in instrument score above by caregivers in rifaximin SSD vs placebo phase	10 weeks
Sickness Impact profile	change in score of the QOL instrument above in placebo vs rifaximin SSD phases	10 weeks
PROMIS-29	change in score of the QOL instrument above in placebo vs rifaximin SSD phases	10 weeks
Safety	Serious adverse event rates in placebo versus rifaximin SSD phases	10 weeks

Collaborators and Investigators

• Sponsor: Jasmohan Bajaj
• Collaborators: Bausch Health Americas, Inc.
• Investigators: Principal Investigator: Jasmohan Bajaj, Richmond VA Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2024
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: December 2, 2024
• First Submitted That Met QC Criteria: December 2, 2024
• First Posted (Actual): December 5, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: dementia; Alzheimer's; vascular dementia; rifaximin; gut-brain
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Neurocognitive Disorders; Tauopathies; Neurodegenerative Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Leukoencephalopathies; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Alzheimer Disease; Dementia; Dementia, Vascular; Anti-Bacterial Agents; Anti-Infective Agents; Gastrointestinal Agents; Rifaximin
• Other Study ID Numbers: 1817324

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not IRB approved to do so

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No