Repurposing Lithium for Parkinson's Disease: a RCT

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Dietary supplement: Lithium; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Thomas Guttuso, MD; Phone Number: 716-932-6080; Email: tguttuso@buffalo.edu
• Study Contact Backup: Name: Amelia Cheney; Phone Number: 716-932-6080; Email: acheney4@buffalo.edu

Study Locations

• United States
  • New York
    • Williamsville, New York, United States, 14221
      • UBMD Neurology
      • Contact: Thomas Guttuso, MD; Phone Number: 716-932-6080; Email: tguttuso@buffalo.edu
      • Contact: Amelia Cheney; Email: acheney4@buffalo.edu
      • Principal Investigator: Thomas Guttuso, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lithium; Lithium: 10mg, 2x/day	Dietary supplement: Lithium; 5mg of elemental lithium/capsule
Placebo Comparator: Placebo; Identical capsules filled with cellulose: 10mg, 2x/day	Other: Placebo; Cellulose-filled capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Serum neurofilament light chain (NfL)	Serum NfL assessed using SIMOA platform by Quanterix (Lexington, MA)	Change from baseline (BL) to 24 week

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Number of patients with any and serious adverse events and number who withdraw from the study.	Throughout 24 week study

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo
• Collaborators: The Cure Parkinson's Trust

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: March 24, 2024
• First Submitted That Met QC Criteria: March 24, 2024
• First Posted (Actual): April 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 24, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Lithium; Parkinson's; Free water; Disease-modifying therapy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antimanic Agents; Lithium Carbonate
• Other Study ID Numbers: STUDY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will be considered on a case-by-case basis.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No