Clinical trial NCT06592014: Lithium for Parkinson's: an Extension Trial
Official title: Repurposing Lithium as a Disease-modifying Therapy in Parkinson's Disease: an Open-label Extension Trial.
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
PHASE2
Conditions: Parkinson Disease
Keywords: lithium
biomarker
free water
neurofilament light chain
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 35
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Free Water
timeFrame: 24 Weeks.
measure: Serum neurofilament light chain
timeFrame: 24 weeks
Secondary outcomes:
measure: Peripheral blood mononuclear cell (PBMC) Nurr1 mRNA levels by real-time polymerase chain reaction (PCR)
timeFrame: 24 weeks
measure: PBMC superoxide dismutase 1 (SOD-1) mRNA levels
timeFrame: 24 weeks
measure: PBMC phosphorylated (p) and total (t) levels of pS9 and total-glycogen synthase kinase 3B (GSK-3B)
timeFrame: 24 weeks
measure: PBMC pThr308, pS473 and t-protein kinase B (Akt)
timeFrame: 24 weeks
measure: Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III
timeFrame: 24 weeks
measure: Parkinson's Anxiety Scale
timeFrame: 24 weeks
measure: Geriatric Depression Scale-15
timeFrame: 24 weeks
measure: Fatigue Severity Scale
timeFrame: 24 weeks
measure: Insomnia Severity Index
timeFrame: 24 weeks
measure: Parkinson's Disease Questionnaire-8
timeFrame: 24 weeks
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Williamsville
country: United States
facility: UBMD Neurology
state: New York
Study officials:
affiliation: University at Buffalo
name: Thomas Guttuso, MD
role: PRINCIPAL_INVESTIGATOR
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.