Repurposing Lithium for Parkinson's Disease
Study Details
Study Description
Brief Summary
This study will examine the effects of lithium aspartate 30-45mg/day on MRI biomarkers and blood-based therapeutic targets among 15 early-stage Parkinson's disease patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
In observational studies, small daily doses of lithium have been associated with a 77% reduced risk of developing Parkinson's disease (PD). In addition, lithium therapy has been effective in preventing neuronal death and behavioral symptoms in several PD animal models. Recently, our group has shown 24-weeks of low-dose lithium aspartate therapy 45mg/day in PD to engage blood-based and the MRI disease progression biomarker, free water, to a greater extent than 15mg/day or 150mg/day of lithium carbonate. However, these blood-based and MRI biomarker findings stem from only four and two PD patients, respectively, who received lithium aspartate 45mg/day. In addition, two other PD patients receiving this dosage withdrew from the study due to side effects of sedation and dizziness. Subsequently, one of these patients who withdrew resumed lithium aspartate at 30mg/day and reported no side effects. Although these findings suggest that this dosage of lithium aspartate has positive effects on PD biomarkers, data from a larger number of PD patients will be required to justify conducting a larger, randomized controlled trial (RCT). The proposed study will enroll 15 additional PD patients over five months who will receive lithium aspartate 30-45mg/day for 24 weeks ensuring that the study will be completed within 12 months. The dosage will be slowly titrated in each patient up to the maximum tolerated dosage in this range. Blood-based biomarkers and MRIs will be assessed at baseline and 24 weeks. It is anticipated that a similar magnitude of biomarker engagement will be observed among these additional 15 patients as was seen in the handful from the pilot study. Such findings would provide strong preliminary evidence to support conducting a larger RCT including both clinical and biomarker outcomes. Positive results from such a RCT would support lithium aspartate as a disease-modifying therapy for PD.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Lithium aspartate Lithium aspartate capsules will be titrated in each patient to the maximum tolerated dosage between 30-45mg/day. |
Dietary Supplement: Lithium aspartate
Lithium aspartate 30-45mg/day
Other Names:
|
Outcome Measures
Primary Outcome Measures
- MRI-derived free water (FW) levels [Change from baseline (BL) to 24 weeks.]
FW in the posterior substantia nigra (pSN), dorsomedial nucleus of the thalamus (DMN-T) and the nucleus basalts of Meynert (nbM).
- Peripheral blood mononuclear cell (PBMC) nuclear receptor-related 1 protein (Nurr1) mRNA expression. [Change from BL to 24 weeks.]
PBMC Nurr1 mRNA expression using Taqman PCR.
Secondary Outcome Measures
- PBMC superoxide dismutase type-1 (SOD-1) mRNA expression [Change from BL to 24 weeks.]
PBMC SOD-1 mRNA expression using Taqman PCR.
- PBMC pS9/total glycogen synthase kinase-3B (GSK-3B) ratio [Change from BL to 24 weeks.]
Assessed using ELISA
- PBMC pThr308 and pS473/total protein kinase B (Akt) ratios [Change from BL to 24 weeks.]
Assessed using ELISA
- Serum interleukin-6 [Change from BL to 24 weeks.]
Assessed using ELISA
- Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination) [Change from BL to 24 weeks.]
Assessed in the "on" state. Score range 0-132 with higher scores indicating worse outcomes.
- Montreal Cognitive Assessment (MoCA) [Change from BL to 24 weeks.]
Score range 0-30 with higher scores indicating better outcomes.
- Parkinson's Anxiety Scale [Change from BL to 24 weeks.]
Score range 0-48 with higher scores indicating worse outcomes.
- Geriatric Depression Scale-15 [Change from BL to 24 weeks.]
Score range 0-15 with higher scores indicating worse outcomes.
- Fatigue Severity Scale [Change from BL to 24 weeks.]
Score range 9-63 with higher scores indicating worse outcomes.
- Insomnia Severity Index [Change from BL to 24 weeks.]
Score range 0-28 with higher scores indicating worse outcomes.
- Parkinson's Disease Questionnaire-8 [Change from BL to 24 weeks.]
Score range 0-32 with higher scores indicating worse outcomes.
- Levodopa equilavent dose [Change from BL to 24 weeks.]
Higher scores indicate higher dose of dopaminergic therapy.
Other Outcome Measures
- Adverse events [Through study completion, an average of 24 weeks.]
Number of patients with serious adverse events and number who withdraw from the study.
Eligibility Criteria
Criteria
Inclusion Criteria:
Have PD for <4 years diagnosed by a movement disorder specialist. Have normal thyroid and renal function at the screening visit. Have no previous exposure to lithium therapy. Have no history of brain surgery. Have no hx of brain imaging findings suggesting another neurological condition besides PD.
Have no use of tobacco or THC products for >1 year. Have stable PD medications for >30 days without current need for adjustments in the investigator's opinion.
Have stable psychiatric and diuretic medications for >60 days with no anticipated need for changes for at least 24 weeks.
Have no active medical or psychiatric condition that may interfere with study procedures in the investigator's opinion.
Exclusion Criteria:
Have PD for >4 years or does not have PD. Have abnormal normal thyroid and renal function at the screening visit. Have previous exposure to lithium therapy. Have history of brain surgery. Have hx of brain imaging findings suggesting another neurological condition besides PD.
Have use of tobacco or THC products within the past year. Have PD medication adjustments within 30 days or needs PD medication adjustments in the investigator's opinion.
Have psychiatric or diuretic medication adjustments within the last 60 days or is anticipated to need changes over next 24 weeks.
Have active medical or psychiatric condition that may interfere with study procedures in the investigator's opinion.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- State University of New York at Buffalo
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- STUDY00007253