This Phase 1/2 clinical trial investigates the repurposing of lithium as a potential disease-modifying therapy for Parkinson's disease (PD). Conducted at SUNY Buffalo under the leadership of Dr. Thomas Guttuso, the study builds on prior observational research suggesting that low-dose lithium may significantly reduce PD risk and slow disease progression.
This Phase 1/2 clinical trial investigates the repurposing of lithium as a potential disease-modifying therapy for Parkinson's disease (PD). Conducted at SUNY Buffalo under the leadership of Dr. Thomas Guttuso, the study builds on prior observational research suggesting that low-dose lithium may significantly reduce PD risk and slow disease progression.
| Attribute | Value |
|-----------|-------|
| NCT Number | NCT06339034 |
| Title | Repurposing Lithium for Parkinson's Disease: a RCT |
| Official Title | Repurposing Lithium as a Disease-modifying Therapy in Parkinson's Disease: A Randomized Controlled Trial |
| Status | Active, Not Recruiting |
| Phase | Phase 1/2 |
| Study Type | Interventional |
| Design | Randomized, Double-blind, Placebo-controlled |
| Allocation | Parallel Group |
| Masking | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Enrollment | 20 patients (estimated) |
| Sponsor | State University of New York at Buffalo |
| Collaborator | Cure Parkinson's |
| Principal Investigator | Thomas Guttuso, MD, Professor of Neurology |
| Location | UBMD Neurology, Williamsville, NY, United States |
| Start Date | July 3, 2024 |
| Primary Completion | December 2025 (estimated) |
| Completion | February 2026 (estimated) |
Large observational studies have demonstrated that low-dose lithium use is associated with a 77% reduced risk of developing Parkinson's disease. This compelling epidemiological data provides a strong rationale for testing lithium in a prospective clinical trial.
Lithium has demonstrated neuroprotective effects in multiple PD animal models:
The research team previously conducted a 24-week pilot study of low-dose lithium in PD patients, which showed improvements in both MRI and blood-based biomarkers. These preliminary findings suggest lithium may slow disease progression, though the sample size was limited (3 of 4 patients receiving MRIs)[@guttuso2023].
| Measure | Description | Timeframe |
|---------|-------------|-----------|
| MRI-derived free water (FW) levels | FW in posterior substantia nigra (pSN), dorsomedial nucleus of the thalamus (DMN-T), and nucleus basalis of Meynert (nbM) | Change from baseline to 24 weeks |
| PBMC Nurr1 mRNA expression | Peripheral blood mononuclear cell nuclear receptor-related 1 protein (Nurr1) expression using Taqman PCR | Change from baseline to 24 weeks |
| Serum neurofilament light chain (NfL) | Assessed using SIMOA platform by Quanterix | Change from baseline to 24 weeks |
| Measure | Description | Timeframe |
|---------|-------------|-----------|
| PBMC SOD-1 mRNA expression | Superoxide dismutase type-1 expression using Taqman PCR | Change from baseline to 24 weeks |
| PBMC pS9/total GSK-3β ratio | Glycogen synthase kinase-3β phosphorylation ratio (ELISA) | Change from baseline to 24 weeks |
| PBMC pThr308 and pS473/total Akt ratios | Protein kinase B phosphorylation ratios (ELISA) | Change from baseline to 24 weeks |
| Serum interleukin-6 | Pro-inflammatory cytokine (ELISA) | Change from baseline to 24 weeks |
| Serum GFAP | Glial fibrillary acidic protein (SIMOA platform) | Change from baseline to 24 weeks |
| MDS-UPDRS Part III | Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Motor Examination (score 0-132, higher = worse) | Change from baseline to 24 weeks |
| MoCA | Montreal Cognitive Assessment (score 0-30, higher = better) | Change from baseline to 24 weeks |
| Parkinson's Anxiety Scale | Score 0-48, higher = worse | Change from baseline to 24 weeks |
| Geriatric Depression Scale-15 | Score 0-15, higher = worse | Change from baseline to 24 weeks |
| Fatigue Severity Scale | Score 9-63, higher = worse | Change from baseline to 24 weeks |
| Insomnia Severity Index | Score 0-28, higher = worse | Change from baseline to 24 weeks |
| PDQ-8 | Parkinson's Disease Questionnaire-8 (score 0-32, higher = worse) | Change from baseline to 24 weeks |
| LEDD | Levodopa equivalent daily dose | Change from baseline to 24 weeks |
Lithium may exert disease-modifying effects in Parkinson's disease through multiple mechanisms:
Free water MRI: The free water imaging technique measures extracellular water in the substantia nigra, which increases as dopaminergic neurons degenerate. Changes in free water may serve as an early marker of neuronal loss.
NfL (Neurofilament Light Chain): A blood biomarker indicating neuronal damage. Lower NfL levels suggest reduced neurodegeneration.
Lithium has been studied extensively in Alzheimer's disease and other neurodegenerative conditions. Its mechanisms include:
The 20mg/day dose used in this trial is significantly lower than doses used for bipolar disorder (typically 600-1200mg/day). This low-dose approach: