This clinical trial investigates whether probiotic supplementation can improve depression symptoms in Parkinson's disease patients. The study targets the gut-brain axis as a modifiable pathway for neuropsychiatric symptoms in PD. Depression is one of the most common non-motor symptoms in PD, affecting up to 50% of patients, and is often undertreated due to the complexity of managing depression alongside motor symptoms and dopaminergic medications.
| Parameter | Value |
|---|---|
| NCT Number | NCT05568498 |
| Phase | Phase 2 |
| Status | Recruiting |
| Intervention | Probiotic blend (Lactobacillus, Bifidobacterium) |
| Dose | Once daily |
| Duration | 12 weeks |
| Sample Size | Approximately 80 participants |
| Primary Endpoint | Change in Beck Depression Inventory (BDI-II) score |
The gut-brain axis is increasingly recognized as a key player in PD pathogenesis[1][2]. This bidirectional communication system involves neural, endocrine, immune, and metabolic pathways connecting the gastrointestinal tract with the central nervous system. In PD, pathological alpha-synuclein aggregates thought to originate in the gut and propagate via the vagus nerve to the brain, representing one of the earliest events in disease development[3].
Key aspects of gut-brain axis involvement in PD include:
Depression affects up to 50% of PD patients and represents one of the most disabling non-motor symptoms[2:1]:
The monoamine hypothesis of depression suggests that dysregulation of serotonin, norepinephrine, and dopamine pathways contributes to depressive symptoms. In PD, dopaminergic neuron loss directly impacts these pathways, creating a unique form of depression that may require targeted interventions beyond traditional antidepressants.
Probiotics may help through multiple mechanisms[5][6][7]:
The specific strains in this trial (Lactobacillus and Bifidobacterium) have been selected based on preclinical evidence showing benefits in alpha-synuclein models and human studies demonstrating safety in PD populations.
Inclusion Criteria
Exclusion Criteria
Primary
Secondary
| Visit | Timing | Assessments |
|---|---|---|
| Screening | Week -2 to 0 | BDI-II, medical history, physical exam |
| Baseline | Week 0 | BDI-II, PDQ-39, MDS-UPDRS, blood draws, stool sample |
| Week 4 | Week 4 | BDI-II, safety assessment |
| Week 8 | Week 8 | BDI-II, PDQ-39, safety assessment |
| Week 12 | Week 12 | All primary and secondary endpoints |
| Follow-up | Week 14 | Safety assessment, adverse event review |
Gut Health Markers
Neurological Markers
Clinical Correlations
Potential Benefits
Challenges
| Agent | Mechanism | Stage | Status |
|---|---|---|---|
| Probiotic (NCT05568498) | Gut microbiome modulation | Phase 2 | Recruiting |
| SSRIs | Serotonin reuptake inhibition | Standard of care | Approved |
| DBS | Deep brain stimulation | Approved | Various targets |
| Ketamine | NMDA antagonism | Experimental | Phase 2 |
| Antidepressants + Psychotherapy | Combined approach | Standard | Approved |
The trial builds on substantial preclinical and clinical evidence:
Preclinical Studies
-Germ-free mice show increased α-synuclein aggregation[5:1]
Human Studies
Multiple trials are investigating gut-brain axis interventions in PD:
Braak H, et al. Gut, origin of Parkinson's disease. Neurobiology of Aging. 2006. ↩︎ ↩︎
Perez-Pardo P, et al. The gut-brain axis in Parkinson's disease. Movement Disorders. 2021. ↩︎ ↩︎
Bjorklund G, et al. Gut-brain axis and alpha-synuclein aggregation. Cellular and Molecular Life Sciences. 2020. ↩︎
Chen Y, et al. Gut microbiota alterations in Parkinson's disease. Journal of Neurology, Neurosurgery & Psychiatry. 2018. ↩︎ ↩︎
Sampson TR, et al. Gut microbiota modulate motor deficits and neuroinflammation in alpha-synucleinopathy. Cell. 2016. ↩︎ ↩︎
Wallace CJ, Milev R. The effects of probiotics on depressive symptoms. Human Psychopharmacology. 2017. ↩︎ ↩︎
Sandhu KV, et al. Gut dysbiosis and neuropsychiatric disorders. Brain Research Bulletin. 2021. ↩︎