Lithium for Parkinson's: an Extension Trial

Repurposing Lithium as a Disease-modifying Therapy in Parkinson's Disease: an Open-label Extension Trial.

This study will examine the effects of 24 weeks of lithium therapy achieving serum lithium levels of 0.25-0.50mmol/L on MRI and blood-based biomarkers in Parkinson's disease patients who have completed one of our current 24-week lithium clinical trials.

Study Overview

• Status: Enrolling by invitation
• Conditions: Parkinson Disease
• Intervention / Treatment: Dietary supplement: Lithium aspartate

Detailed Description

In observational studies, small daily doses of lithium from smoking cigarettes 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 be associated with improvements in both MRI and blood-based biomarkers implying that lithium may be slowing the progression of the disease. However, these findings stemmed from only three of four patients receiving MRIs. Our group is now conducting two larger studies enrolling a total of 35 PD patients who are being treated with either 45mg/day or 20mg/day of lithium or placebo therapy for 24 weeks. Because our earlier study showed maximum improvements in PD biomarkers in patients with serum lithium levels of 0.25-0.50mmol/L and there are large interpatient variations in serum lithium levels achieved from the same lithium dosage, this present study will adjust lithium dosing in each patient to achieve this target serum lithium level for an additional 24 weeks. MRI and blood-based biomarker changes from Baseline will be compared in patients with serum lithium levels ≥ 0.25mmol/L and <0.25mmol/L from one of the 24-week studies and within individual patients. Results from this study may identify a target serum lithium level range associated with maximum improvements in PD biomarkers that can be used in the design of future, larger lithium PD lithium trials, which may eventually support lithium as a disease-modifying therapy for PD that could improve patients' long-term prognoses.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Williamsville, New York, United States, 14221
      • UBMD Neurology

Participation Criteria

Eligibility Criteria

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

Description

1. All PD patients completing STUDY00007253 or STUDY00008239 at the University at Buffalo will be eligible.
2. No unstable cardiac, medical, neurologic or psychiatric condition in the opinion of the PI.
3. No current use of illicit drugs or current alcohol abuse in the opinion of the PI.
4. No history of brain surgery or possible need for brain surgery including deep brain stimulation (DBS) for at least 24 weeks in the opinion of the PI.
5. Women with child bearing potential will need a negative pregnancy test and not be nursing an infant at screening. Women with child bearing potential will need to report using barrier method or hormonal contraception.
6. Willing and able to sign informed consent and follow study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lithium aspartate; Lithium aspartate with dosage adjusted to achieve a serum lithium level of 0.25-0.50mmol/L	Dietary supplement: Lithium aspartate; Lithium aspartate with dosage adjusted to serum lithium level 0.25-0.50mmol/L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free Water	Change in MRI-assessed free water in posterior substantia nigra, dorsomedial nucleus of the thalamus and nucleus basalts of Meynert.	24 Weeks.
Serum neurofilament light chain	Change in serum neurofilament light chain	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral blood mononuclear cell (PBMC) Nurr1 mRNA levels by real-time polymerase chain reaction (PCR)	Change in PBMC Nurr1	24 weeks
PBMC superoxide dismutase 1 (SOD-1) mRNA levels	Change in PBMC SOD-1	24 weeks
PBMC phosphorylated (p) and total (t) levels of pS9 and total-glycogen synthase kinase 3B (GSK-3B)	Change in PBMC pS9 and t-GSK-3B	24 weeks
PBMC pThr308, pS473 and t-protein kinase B (Akt)	Change in pThr308, pS473 and t-Akt	24 weeks
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III	Change in MDS-UPDRS part III scores, Assessed in the "on" state. Score range 0-132 with higher scores indicating worse outcomes.	24 weeks
Parkinson's Anxiety Scale	Change in Parkinson's Anxiety Scale scores, Score range 0-48 with higher scores indicating worse outcomes.	24 weeks
Geriatric Depression Scale-15	Change in Geriatric Depression Scale-15 scores, Score range 0-15 with higher scores indicating worse outcomes.	24 weeks
Fatigue Severity Scale	Change in Fatigue Severity Scale scores, Score range 9-63 with higher scores indicating worse outcomes.	24 weeks
Insomnia Severity Index	Change in Insomnia Severity Index, Score range 0-28 with higher scores indicating worse outcomes.	24 weeks
Parkinson's Disease Questionnaire-8	Change in Parkinson's Disease Questionnaire-8 scores, Score range 0-32 with higher scores indicating worse outcomes.	24 weeks
Montreal Cognitive Assessment (MoCA)	Change in Montreal Cognitive Assessment (MoCA) version 1 and 2 scores, Score range 0-30 with higher scores indicating better outcomes.	24 weeks

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo
• Investigators: Principal Investigator: Thomas Guttuso, MD, University at Buffalo

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 (Actual): August 9, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: September 8, 2024
• First Submitted That Met QC Criteria: September 8, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: biomarker; lithium; neurofilament light chain; free water
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Charcot-Marie-Tooth disease, Type 1F; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Excitatory Amino Acid Agonists; Excitatory Amino Acid Agents; N-Methylaspartate
• Other Study ID Numbers: STUDY00008239

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient demographics and outcome measure results.
• IPD Sharing Time Frame: IPD will be made available after the study results are published.
• IPD Sharing Access Criteria: Researchers who have requested IPD from the PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No