The Rifaximin in Dementia Trial (RIDE) is a Phase 1/2 clinical trial investigating the effects of rifaximin, a non-absorbable antibiotic, on patients with Alzheimer's disease (AD) and vascular dementia (VaD). This trial represents a novel approach targeting the gut-brain axis to potentially modify dementia progression[1].
Rifaximin is a gut-targeted antibiotic that acts locally in the gastrointestinal tract with minimal systemic absorption. By modulating the gut microbiome, this trial tests the hypothesis that improving gut microbial function can reduce systemic inflammation and positively impact cognitive function in dementia patients.
| Attribute | Value |
|---|---|
| NCT Number | NCT06718686 |
| Phase | Phase 1/2 |
| Status | Recruiting |
| Enrollment | 20 patients (estimated) |
| Study Type | Interventional |
| Design | Sequential allocation, triple-blind (participant, care provider, outcomes assessor) |
| Start Date | December 30, 2024 |
| Primary Completion | December 2025 (estimated) |
| Completion | May 2026 (estimated) |
Rifaximin SSD therapy is safe and well tolerated in patients with Alzheimer's disease and vascular dementia, with beneficial changes in systemic inflammation and biomarkers of dementia due to improvement in microbiota function compared to placebo.
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:
Rifaximin exerts its potential therapeutic effects through multiple mechanisms related to the gut-brain axis:
Rifaximin is an ideal candidate for gut-brain axis therapy because:
Sequential design where patients receive both placebo and active drug in a masked sequence.
Triple-blind design where participants, care providers, and outcome assessors are masked to treatment assignment.
| Arm | Intervention |
|---|---|
| Placebo | Placebo tablet BID |
| Rifaximin SSD 40mg IR BID | Rifaximin SSD 40 mg IR tablet BID |
10 weeks total (including both placebo and active treatment phases)
| Measure | Description | Time Frame |
|---|---|---|
| Change in stool and serum short-chain fatty acid levels | SCFA in stool and serum: rifaximin SSD phase vs placebo phase | 10 weeks |
| Change in bile acids in stool and serum | Bile acids: rifaximin SSD phase vs placebo phase | 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Systemic inflammatory change | Serum LBP, inflammatory cytokines (IL-6, TNF-α, IL-10, IL-1β) | 10 weeks |
| Stool microbiome composition | 16SrRNA microbiome composition and diversity | 10 weeks |
| Dementia biomarkers | Plasma Aβ42, Aβ40, Aβ42/40 ratio, p-tau181 | 10 weeks |
| MMSE | Change in Mini-Mental State Examination | 10 weeks |
| Cognitive testing (PHES) | Psychometric Hepatic Encephalopathy Score | 10 weeks |
| CDR-SB | Clinical Dementia Rating - Sum of Boxes | 10 weeks |
| EncephalApp Stroop performance | Off time and on time performance | 10 weeks |
| Critical flicker fusion analysis | CFF threshold | 10 weeks |
| Katz Index of Independence in ADL | Activity of Daily Living | 10 weeks |
| Lawton-Brody IADL | Instrumental Activities of Daily Living | 10 weeks |
| Zarit Burden Interview | Caregiver burden | 10 weeks |
| Sickness Impact profile | Quality of Life | 10 weeks |
| PROMIS-29 | Patient-Reported Outcomes Measurement Information System | 10 weeks |
| Safety | Serious adverse event rates | 10 weeks |
This trial is significant because it directly tests the gut-brain axis hypothesis in neurodegenerative diseases. Emerging evidence suggests that:
The trial includes comprehensive biomarker assessments:
If successful, this trial could: