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.
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.
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.
Parallel
tributyrin
Dietary supplementParticipants 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.
Placebo
Other interventionThe placebo will consist of potato starch encapsulated under identical conditions to those used for the tributyrin capsules, ensuring adequate blinding of the study.
Montreal Cognitive Assessment (MoCA)
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.
Levels of SCFAs (Acetate, Propionate and Butyrate) in faeces
To evaluate whether butyrate supplementation promotes increased levels of SCFAs, levels of acetate, propionate and butyrate will be measured. Faecal samples will be collected before, after 12 months, and three months post-intervention. Faecal samples will be collected in a home setting using tubes containing a stabilizing medium. The tubes will be hermetically sealed to minimize the risk of SCFAs volatilization and ensure sample integrity. SCFA levels will be quantified using gas chromatography-mass spectrometry (GC-MS) (Agilent Technologies). The units of measure for SCFAs will be expressed in µmol/g of faeces.
Intestinal permeability
Plasma ZO-1, a core tight-junction scaffold protein, will be quantified as its reduction reflects epithelial structural loss; decreased butyrate availability is known to downregulate ZO-1 expression and increase paracellular permeability. To complement this structural indicator, LPS-binding protein (LBP) will be measured as the primary marker of systemic exposure to gut-derived LPS, representing the canonical downstream pathway of barrier dysfunction that activates TLR4-NF-κB signaling implicated in AD-related neuroimmune activation. Intestinal fatty-acid-binding protein 2 (I-FABP2) will also be assessed as a sensitive indicator of enterocyte membrane integrity. Samples will be analyzed by ELISA kits for ZO-1 (Catalog: EEL211), for LBP (Catalog: EH297RB) and for I-FABP2 (Catalog: EHFABP2) from Thermo Fisher (California, USA). The samples will be stored at -80°C until analysis. Protein levels will be measured in pg/mL.
Systemic inflammation
Due to butyrate has demonstrated the ability to inhibit pro-inflammatory cytokines while promoting the production of anti-inflammatory cytokines as well as reduce oxidative stress markers. The levels of IL-1β, IL-6 TNF-α, IL-10 cytokines. Blood samples will be collected from participants to assess the mentioned cytokines at baseline, at the end of the 12-week intervention, and three months after its conclusion using ELISA kits following the manufacturer's instructions (Thermo Fisher, California, USA). Blood samples will be collected at three points. After the sample collection, they will be centrifuged at 2000 x g for 15 minutes, the serum will be obtained, and the blood samples will be stored at -80°C for subsequent analysis. Cytokine levels will be quantified in pg/mL.
Serum levels of NfL
Neurofilament light chain (NfL) will be assessed as a robust indicator of large-caliber axonal injury, commonly elevated in contexts of microglial activation and peripheral inflammatory signaling. Plasma NfL will be quantified using commercial ELISA kits following manufacturer instructions (Catalog. for NfL: BMS2362 from Thermo Fisher. The levels will be quantified in pg/mL.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
