Tributyrin Treatment in Mild Alzheimer Disease: Assessment of Butyrate Effects Via the Gut-Brain
Trial Snapshot
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Universidad de Almeria
- Enrollment
- 156
- Locations
- 1
- Primary Endpoint
- Montreal Cognitive Assessment (MoCA)
Study Overview
Brief Summary
The goal of this clinical trial is to learn if tributyrin can help prevent or mitigate cognitive decline in individuals with mild Alzheimer's disease (AD). The trial will also examine the safety and effects of tributyrin on inflammation and gut microbiota. The main questions it aims to answer are:
Does tributyrin reduce inflammation and neurodegeneration markers? How does tributyrin affect gut microbiota and intestinal permeability? Researchers will compare tributyrin to a placebo (a look-alike substance that contains no active ingredient) to evaluate its effectiveness.
Participants will:
Take tributyrin or a placebo every day for 12 weeks. Undergo assessments of cognitive function, blood markers (such as NfL and pTau217), and gut health.
The findings are expected to provide insight into the potential of tributyrin as a preventive intervention for Alzheimer's disease.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Masking Description
The process of random assignment of participants will be carried out using opaque envelopes containing the assignment to the butyrate group (experimental group) and the CG group (control group).
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •individuals diagnosed with mild AD within the past year (ICD-10: F00.1).
- •voluntary consent to participate in the study in accordance with the Declaration of Helsinki.
- •not currently enrolled in any other clinical trial that could confound the results.
Exclusion Criteria
- •individuals with other potential causes of dementia, such as a history of severe traumatic brain injury, brain tumours, epilepsy, or central nervous system infections.
- •individuals involved in an intervention that interferes with the trial (immunosuppressive drugs, steroids, antibiotics, or received chemotherapy in the month prior to the start of the intervention).
- •individuals with gastrointestinal disorders.
Arms & Interventions
Placebo
The placebo will consist of potato starch encapsulated under identical conditions to those used for the tributyrin capsules, ensuring adequate blinding of the study. The administration of the placebo will follow the same protocol as that of the intervention group.
Tributyrin
Participants will receive 1 capsule per day for 12 weeks. Each capsule contains 450 mg of tributyrins. The capsules will have a gelatin coating. In the market, formulations are available with dosages ranging from 200 to 500 mg.
Intervention: tributyrin (Dietary Supplement)
Outcomes
Primary Outcomes
Montreal Cognitive Assessment (MoCA)
Time Frame: Change from Baseline to 12 weeks and 24 weeks
For cognitive evaluation, the Montreal Cognitive Assessment (MoCA) will be utilized, a widely recognized tool developed to identify mild cognitive impairment. In comparison to the Mini-Mental State Examination (MMSE), MoCA exhibits greater sensitivity, particularly in the early stages of AD, allowing for the detection of deficits in areas such as attention, memory, language, abstraction, and executive functions The MoCA is assessed on a scale ranging from 0 to 30, where higher scores reflect superior cognitive performance. A score of 26 or higher is typically regarded as within the normal range, whereas lower scores indicate different levels of cognitive impairment.
Secondary Outcomes
- Accuracy in KEFS test (Cognitive flexibility)(Change from Baseline to 12 weeks and 24 weeks)
- Accuracy in N-back Task (Working Memory)(Change from Baseline to 12 weeks and 24 weeks)
- Reaction Time in N-back Task (Working Memory)(Change from Baseline to 12 weeks and 24 weeks)
- Verbal memory by Rey Test(Change from Baseline to 12 weeks and 24 weeks)
- Visual memory by Rey Test(Change from Baseline to 12 weeks and 24 weeks)
- Reaction time in Stroop Test (Attention)(Change from Baseline to 12 weeks and 24 weeks)
- Accuracy in Stroop Test (Attention)(Change from Baseline to 12 weeks and 24 weeks)
- Completion Time in KEFS test (Cognitive flexibility)(Change from Baseline to 12 weeks and 24 weeks)
- Accuracy in Go/No-Go test (Inhibition)(Change from Baseline to 12 weeks and 24 weeks)
- Reaction time in Go/No-Go test (Inhibition)(Change from Baseline to 12 weeks and 24 weeks)
- Executive functions and impulsivity(Change from Baseline to 12 weeks and 24 weeks)
- Neuropsychiatric Inventory Questionnaire (NPI-Q)(Change from Baseline to 12 weeks and 24 weeks)
- Systemic inflammation(Change from Baseline to 12 weeks and 24 weeks)
- Composition of Intestinal Microbiota (16S rRNA Gene Sequencing)(Change from Baseline to 12 weeks and 24 weeks)
- Composition of Intestinal Microbiota (16S rRNA Gene Sequencing)(Change from Baseline to 12 weeks and 24 weeks)
- Verbal memory by Rey Test(Change from Baseline to 12 weeks and 24 weeks)
- Sustained attention by CPT(Change from baseline to 12 weeks and 24 weeks)
- Reaction time in Stroop Test (Attention)(Change from Baseline to 12 weeks and 24 weeks)
- Accuracy in Stroop Test (Attention)(Change from Baseline to 12 weeks and 24 weeks)
- Completion Time in KEFS test (Cognitive flexibility)(Change from Baseline to 12 weeks and 24 weeks)
- Accuracy in KEFS test (Cognitive flexibility)(Change from Baseline to 12 weeks and 24 weeks)
- Accuracy in Go/No-Go test (Inhibition)(Change from Baseline to 12 weeks and 24 weeks)
- Reaction time in Go/No-Go test (Inhibition)(Change from Baseline to 12 weeks and 24 weeks)
- Executive functions and impulsivity(Change from Baseline to 12 weeks and 24 weeks)
- Neuropsychiatric Inventory Questionnaire (NPI-Q)(Change from Baseline to 12 weeks and 24 weeks)
- Levels of SCFAs (Acetate, Propionate and Butyrate) in faeces(Change from Baseline to 12 weeks and 24 weeks)
- Intestinal permeability(Change from Baseline to 12 weeks and 24 weeks)
- Systemic inflammation(Change from Baseline to 12 weeks and 24 weeks)
- Serum levels of NfL(Change from baseline to 12 weeks and 24 weeks)
- Serum levels of pTau217(Change from Baseline to 12 weeks and 24 weeks)
- Serum levels of Amyloid42/40 ratio(Change from Baseline to 12 weeks and 24 weeks)
- Accuracy in N-back Task (Working Memory)(Change from Baseline to 12 weeks and 24 weeks)
- Reaction Time in N-back Task (Working Memory)(Change from Baseline to 12 weeks and 24 weeks)
- Visual memory by Rey Test(Change from Baseline to 12 weeks and 24 weeks)
Investigators
Pablo Román López
Associate Professor, Dean of the Faculty of Health Sciences
Universidad de Almeria