Repurposing Lithium for Parkinson's Disease: a RCT

Parkinson Disease Clinical Trial

Official title:

Repurposing Lithium as a Disease-modifying Therapy in Parkinson's Disease: A Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06339034
• Other study ID #: STUDY
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2024
• Est. completion date: October 2025

Study information

• Verified date: March 2024
• Source: State University of New York at Buffalo
• Contact: Thomas Guttuso, MD
• Phone: 716-932-6080
• Email: tguttuso[@]buffalo.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: October 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Dietary Supplement:
• Lithium
5mg of elemental lithium/capsule

Other:
• Placebo
Cellulose-filled capsules

Locations

Country	Name	City	State
United States	UBMD Neurology	Williamsville	New York

Sponsors (2)

Lead Sponsor	Collaborator
State University of New York at Buffalo	The Cure Parkinson's Trust

Country where clinical trial is conducted

United States, 

References & Publications (1)

Guttuso T Jr, Shepherd R, Frick L, Feltri ML, Frerichs V, Ramanathan M, Zivadinov R, Bergsland N. Lithium's effects on therapeutic targets and MRI biomarkers in Parkinson's disease: A pilot clinical trial. IBRO Neurosci Rep. 2023 May 7;14:429-434. doi: 10.1016/j.ibneur.2023.05.001. eCollection 2023 Jun. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events	Number of patients with any and serious adverse events and number who withdraw from the study.	Throughout 24 week study
Primary	MRI-derived free water (FW) levels.	FW in the posterior substantia nigra (pSN), dorsomedial nucleus of the thalamus (DMN-T) and the nucleus basalts of Meynert (nbM).	Change from baseline (BL) to 24 week
Primary	Peripheral blood mononuclear cell (PBMC) nuclear receptor-related 1 protein (Nurr1) mRNA expression	PBMC Nurr1 mRNA expression using Taqman PCR.	Change from baseline (BL) to 24 week
Primary	Serum neurofilament light chain (NfL)	Serum NfL assessed using SIMOA platform by Quanterix (Lexington, MA)	Change from baseline (BL) to 24 week
Secondary	PBMC superoxide dismutase type-1 (SOD-1) mRNA expression	PBMC SOD-1 mRNA expression using Taqman PCR	Change from baseline (BL) to 24 week
Secondary	PBMC pS9/total glycogen synthase kinase-3B (GSK-3B) ratio	Assessed using ELISA	Change from baseline (BL) to 24 week
Secondary	PBMC pThr308 and pS473/total protein kinase B (Akt) ratios	Assessed using ELISA	Change from baseline (BL) to 24 week
Secondary	Serum interleukin-6	Assessed using ELISA	Change from baseline (BL) to 24 week
Secondary	Serum glial fibrillary acidic protein (GFAP)	Serum GFAP assessed using SIMOA platform by Quanterix (Lexington, MA)	Change from baseline (BL) to 24 week
Secondary	Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination)	Assessed in the "on" state. Score range 0-132 with higher scores indicating worse outcomes.	Change from baseline (BL) to 24 week
Secondary	Montreal Cognitive Assessment (MoCA)	Score range 0-30 with higher scores indicating better outcomes.	Change from baseline (BL) to 24 week
Secondary	Parkinson's Anxiety Scale	Score range 0-48 with higher scores indicating worse outcomes.	Change from baseline (BL) to 24 week
Secondary	Geriatric Depression Scale-15	Score range 0-15 with higher scores indicating worse outcomes.	Change from baseline (BL) to 24 week
Secondary	Fatigue Severity Scale	Score range 9-63 with higher scores indicating worse outcomes.	Change from baseline (BL) to 24 week
Secondary	Insomnia Severity Index	Score range 0-28 with higher scores indicating worse outcomes.	Change from baseline (BL) to 24 week
Secondary	Parkinson's Disease Questionnaire-8	Score range 0-32 with higher scores indicating worse outcomes.	Change from baseline (BL) to 24 week
Secondary	Levodopa equivalent daily dose (LEDD)	Higher scores indicate higher dose of dopaminergic therapy.	Change from baseline (BL) to 24 week