Dementia Alzheimer Type, Dementia Associated With Cerebrovascular Disease
Conditions
Keywords
dementia, rifaximin, gut-brain, Alzheimer's, vascular dementia
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.
Interventions
Drug therapy vs placebo
DRUGPlacebo
Placebo drug
Sponsors
Jasmohan Bajaj
Bausch Health Americas, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Contacts
CONTACTJasmohan S Bajaj, MD
CONTACTHaley Obolewicz, RN
PRINCIPAL_INVESTIGATORJasmohan Bajaj
Richmond VA Medical Center
Outcome results
None listed