Rifaximin SSD in Dementia Trial

Phase 1

Recruiting

• Conditions: Dementia Alzheimer Type; Dementia Associated With Cerebrovascular Disease
• Interventions: Drug: Placebo; Drug: Rifaximin SSD 40 mg IR tablet

• Registration Number: NCT06718686
• Lead Sponsor: Jasmohan Bajaj

Brief Summary

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.

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 Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-02
• Study First Submitted QC: 2024-12-02
• Study First Posted: 2024-12-05
• Study Start: 2024-12-30
• Last Update Submitted: 2024-12-30
• Last Update Posted: 2024-12-31
• Primary Completion: 2025-12
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients will be given placebo and actual drug sequentially with the order hidden
Rifaximin SSD 40mg IR BID	Rifaximin SSD 40 mg IR tablet	Patients will be given placebo and actual drug sequentially with the order hidden

Primary Outcome Measures

Name	Time	Method
Change in stool and serum short-chain fatty acid levels	10 weeks	Change in SCFA in stool and serum in rifaximin SSD phase vs placebo phase
Change in bile acids in stool and serum	10 weeks	Change in bile acids in stool and serum in rifaximin SSD phase vs placebo phase

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Richmond VA Medical Center; 🇺🇸 Richmond, Virginia, United States