Clinical trial NCT06339034: Repurposing Lithium for Parkinson's Disease: a RCT
Official title: Repurposing Lithium as a Disease-modifying Therapy in Parkinson's Disease: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Parkinson Disease
Keywords: Parkinson's
Lithium
Free water
Disease-modifying therapy
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
Collaborators: name: Cure Parkinson's
First posted: 2024-04-01
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, placebo-controlled
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: MRI-derived free water (FW) levels.
timeFrame: Change from baseline (BL) to 24 week
measure: Peripheral blood mononuclear cell (PBMC) nuclear receptor-related 1 protein (Nurr1) mRNA expression
timeFrame: Change from baseline (BL) to 24 week
measure: Serum neurofilament light chain (NfL)
timeFrame: Change from baseline (BL) to 24 week
Secondary outcomes:
measure: PBMC superoxide dismutase type-1 (SOD-1) mRNA expression
timeFrame: Change from baseline (BL) to 24 week
measure: PBMC pS9/total glycogen synthase kinase-3B (GSK-3B) ratio
timeFrame: Change from baseline (BL) to 24 week
measure: PBMC pThr308 and pS473/total protein kinase B (Akt) ratios
timeFrame: Change from baseline (BL) to 24 week
measure: Serum interleukin-6
timeFrame: Change from baseline (BL) to 24 week
measure: Serum glial fibrillary acidic protein (GFAP)
timeFrame: Change from baseline (BL) to 24 week
measure: Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination)
timeFrame: Change from baseline (BL) to 24 week
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: Change from baseline (BL) to 24 week
measure: Parkinson's Anxiety Scale
timeFrame: Change from baseline (BL) to 24 week
measure: Geriatric Depression Scale-15
timeFrame: Change from baseline (BL) to 24 week
measure: Fatigue Severity Scale
timeFrame: Change from baseline (BL) to 24 week
measure: Insomnia Severity Index
timeFrame: Change from baseline (BL) to 24 week
measure: Parkinson's Disease Questionnaire-8
timeFrame: Change from baseline (BL) to 24 week
measure: Levodopa equivalent daily dose (LEDD)
timeFrame: Change from baseline (BL) to 24 week
Other outcomes:
measure: Adverse events
timeFrame: Throughout 24 week study
Locations:
city: Williamsville
country: United States
facility: UBMD Neurology
state: New York
Study officials:
References:
citation: 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.