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Lithium for Parkinson's: an Extension Trial

Phase 1
Conditions
Parkinson Disease
Interventions
Dietary Supplement: Lithium aspartate
Registration Number
NCT06592014
Lead Sponsor
State University of New York at Buffalo
Brief Summary

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.

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.

Recruitment & Eligibility

Status
ENROLLING_BY_INVITATION
Sex
All
Target Recruitment
35
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Lithium aspartateLithium aspartateLithium aspartate with dosage adjusted to achieve a serum lithium level of 0.25-0.50mmol/L
Primary Outcome Measures
NameTimeMethod
Free Water24 Weeks.

Change in MRI-assessed free water in posterior substantia nigra, dorsomedial nucleus of the thalamus and nucleus basalts of Meynert.

Serum neurofilament light chain24 weeks

Change in serum neurofilament light chain

Secondary Outcome Measures
NameTimeMethod
Peripheral blood mononuclear cell (PBMC) Nurr1 mRNA levels by real-time polymerase chain reaction (PCR)24 weeks

Change in PBMC Nurr1

PBMC superoxide dismutase 1 (SOD-1) mRNA levels24 weeks

Change in PBMC SOD-1

PBMC phosphorylated (p) and total (t) levels of pS9 and total-glycogen synthase kinase 3B (GSK-3B)24 weeks

Change in PBMC pS9 and t-GSK-3B

PBMC pThr308, pS473 and t-protein kinase B (Akt)24 weeks

Change in pThr308, pS473 and t-Akt

Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III24 weeks

Change in MDS-UPDRS part III scores, Assessed in the "on" state. Score range 0-132 with higher scores indicating worse outcomes.

Parkinson's Anxiety Scale24 weeks

Change in Parkinson's Anxiety Scale scores, Score range 0-48 with higher scores indicating worse outcomes.

Geriatric Depression Scale-1524 weeks

Change in Geriatric Depression Scale-15 scores, Score range 0-15 with higher scores indicating worse outcomes.

Fatigue Severity Scale24 weeks

Change in Fatigue Severity Scale scores, Score range 9-63 with higher scores indicating worse outcomes.

Insomnia Severity Index24 weeks

Change in Insomnia Severity Index, Score range 0-28 with higher scores indicating worse outcomes.

Parkinson's Disease Questionnaire-824 weeks

Change in Parkinson's Disease Questionnaire-8 scores, Score range 0-32 with higher scores indicating worse outcomes.

Montreal Cognitive Assessment (MoCA)24 weeks

Change in Montreal Cognitive Assessment (MoCA) version 1 and 2 scores, Score range 0-30 with higher scores indicating better outcomes.

Trial Locations

Locations (1)

UBMD Neurology

🇺🇸

Williamsville, New York, United States

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