Repurposing Lithium for Parkinson's Disease: a RCT

Phase 1

Recruiting

Conditions: Parkinson Disease

Interventions: Other: Placebo
Dietary Supplement: Lithium

Registration Number: NCT06339034

Lead Sponsor: State University of New York at Buffalo

Brief Summary: This study will examine the effects of lithium 20mg/day compared to placebo on MRI and blood-based biomarkers among 20 early-stage Parkinson's disease patients.

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 therapy in PD to improve both MRI and blood-based biomarkers implying that lithium may be slowing the progression of the disease. However, these findings stem from only three of four patients receiving MRIs. A larger study will be required to determine if these promising results can be replicated. The proposed study will enroll 20 additional PD patients who will be randomly assigned to receive either lithium 20mg/day or identically-appearing placebo capsules for 24 weeks. This will be a double-blind study meaning that neither the patients nor the study team will know to which therapy patients have been assigned. Positive results from this study will support further research on lithium that could eventually support lithium as a disease-modifying therapy for PD that could improve patients' long-term prognoses.

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 20

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Identical capsules filled with cellulose: 10mg, 2x/day
Lithium	Lithium	Lithium: 10mg, 2x/day

Primary Outcome Measures

Name	Time	Method
Peripheral blood mononuclear cell (PBMC) nuclear receptor-related 1 protein (Nurr1) mRNA expression	Change from baseline (BL) to 24 week	PBMC Nurr1 mRNA expression using Taqman PCR.
MRI-derived free water (FW) levels.	Change from baseline (BL) to 24 week	FW in the posterior substantia nigra (pSN), dorsomedial nucleus of the thalamus (DMN-T) and the nucleus basalts of Meynert (nbM).
Serum neurofilament light chain (NfL)	Change from baseline (BL) to 24 week	Serum NfL assessed using SIMOA platform by Quanterix (Lexington, MA)

Secondary Outcome Measures

Name	Time	Method
PBMC pS9/total glycogen synthase kinase-3B (GSK-3B) ratio	Change from baseline (BL) to 24 week	Assessed using ELISA
PBMC pThr308 and pS473/total protein kinase B (Akt) ratios	Change from baseline (BL) to 24 week	Assessed using ELISA
Parkinson's Anxiety Scale	Change from baseline (BL) to 24 week	Score range 0-48 with higher scores indicating worse outcomes.
Fatigue Severity Scale	Change from baseline (BL) to 24 week	Score range 9-63 with higher scores indicating worse outcomes.
PBMC superoxide dismutase type-1 (SOD-1) mRNA expression	Change from baseline (BL) to 24 week	PBMC SOD-1 mRNA expression using Taqman PCR
Insomnia Severity Index	Change from baseline (BL) to 24 week	Score range 0-28 with higher scores indicating worse outcomes.
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination)	Change from baseline (BL) to 24 week	Assessed in the "on" state. Score range 0-132 with higher scores indicating worse outcomes.
Serum interleukin-6	Change from baseline (BL) to 24 week	Assessed using ELISA
Geriatric Depression Scale-15	Change from baseline (BL) to 24 week	Score range 0-15 with higher scores indicating worse outcomes.
Levodopa equivalent daily dose (LEDD)	Change from baseline (BL) to 24 week	Higher scores indicate higher dose of dopaminergic therapy.
Serum glial fibrillary acidic protein (GFAP)	Change from baseline (BL) to 24 week	Serum GFAP assessed using SIMOA platform by Quanterix (Lexington, MA)
Montreal Cognitive Assessment (MoCA)	Change from baseline (BL) to 24 week	Score range 0-30 with higher scores indicating better outcomes.
Parkinson's Disease Questionnaire-8	Change from baseline (BL) to 24 week	Score range 0-32 with higher scores indicating worse outcomes.

Trial Locations

Locations (1): UBMD Neurology
🇺🇸
Williamsville, New York, United States

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