This clinical trial investigates whether probiotic supplementation can improve cognitive function and reduce neuroinflammation in patients with mild Alzheimer's disease (AD). The study targets the gut-brain axis as a modifiable pathway for neurodegeneration, based on emerging evidence that gut microbiota composition influences brain function and neuroinflammation[@Sampson2016][@bonfili2020].
The gut-brain axis is a bidirectional communication network connecting the gastrointestinal tract to the central nervous system. This communication occurs through multiple pathways including the vagus nerve, immune system signaling, microbial metabolites, and endocrine pathways. In neurodegenerative diseases, dysbiosis (imbalance in gut microbiota) has been associated with increased intestinal permeability ("leaky gut"), systemic inflammation, and neuroinflammation[@kim2021][@paoli2020].
This clinical trial investigates whether probiotic supplementation can improve cognitive function and reduce neuroinflammation in patients with mild Alzheimer's disease (AD). The study targets the gut-brain axis as a modifiable pathway for neurodegeneration, based on emerging evidence that gut microbiota composition influences brain function and neuroinflammation[@Sampson2016][@bonfili2020].
The gut-brain axis is a bidirectional communication network connecting the gastrointestinal tract to the central nervous system. This communication occurs through multiple pathways including the vagus nerve, immune system signaling, microbial metabolites, and endocrine pathways. In neurodegenerative diseases, dysbiosis (imbalance in gut microbiota) has been associated with increased intestinal permeability ("leaky gut"), systemic inflammation, and neuroinflammation[@kim2021][@paoli2020].
| Parameter | Value |
|-----------|-------|
| NCT Number | NCT06181513 |
| Phase | Early Phase 1 |
| Status | Recruiting |
| Sponsor | University of Nicosia |
| Collaborator | Cyprus Institute of Neurology and Genetics |
| Principal Investigator | Nicoletta Nicolaou, Associate Professor |
| Enrollment | 40 patients |
| Study Type | Interventional |
| Allocation | Randomized |
| Intervention Model | Parallel |
| Masking | Triple (Participant, Care Provider, Investigator) |
| Start Date | December 19, 2022 |
| Primary Completion | July 1, 2025 (Estimated) |
| Completion Date | December 1, 2025 (Estimated) |
| Duration | 16 weeks |
| Location | Nicosia, Cyprus |
The probiotic intervention in this trial aims to modulate the gut-brain axis through multiple mechanisms:
The trial uses Ultrabiotique Equilibre 30 Vitavea, containing:
Preclinical studies in APP/PS1 transgenic mice (a model of AD) have shown that probiotic supplementation:
| Arm | Type | Description |
|-----|------|-------------|
| Probiotics | Experimental | 1 capsule daily of probiotic blend for 16 weeks |
| Placebo | Placebo Comparator | 1 capsule daily of placebo for 16 weeks |
| Measure | Assessment | Timepoints |
|---------|------------|------------|
| Cognitive function | Mini-Mental State Examination (MMSE) | Week 0, Week 16 |
| Cognitive function | Montreal Cognitive Assessment (MoCA) | Week 0, Week 16 |
| Cognitive function | Rey-Osterrieth Complex Figure Test | Week 0, Week 16 |
| Cognitive function | Wechsler Abbreviated Scale of Intelligence (WASI) | Week 0, Week 16 |
| Neurophysiological activity | Electroencephalogram (EEG) | Week 0, Week 16 |
| Neurophysiological activity | Electrocardiogram (EKG) | Week 0, Week 16 |
| Microbiome profile | 16S rDNA gene sequencing | Week 0 |
| Dietary habits | Food Frequency Questionnaire (confounding) | Week 0 |
Principal Investigator: Nicoletta Nicolaou
This trial addresses several key questions in AD therapeutics:
If successful, this approach could provide a simple, safe, and inexpensive adjunct therapy for AD patients.