Parkinson Disease
Conditions
Keywords
lithium, biomarker, free water, neurofilament light chain
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.
Interventions
DIETARY_SUPPLEMENTLithium aspartate
Lithium aspartate with dosage adjusted to serum lithium level 0.25-0.50mmol/L
Sponsors
State University of New York at Buffalo
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Free Water | 24 Weeks. | Change in MRI-assessed free water in posterior substantia nigra, dorsomedial nucleus of the thalamus and nucleus basalts of Meynert. |
| Serum neurofilament light chain | 24 weeks | Change in serum neurofilament light chain |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 levels | 24 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 III | 24 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 Scale | 24 weeks | Change in Parkinson's Anxiety Scale scores, Score range 0-48 with higher scores indicating worse outcomes. |
| Geriatric Depression Scale-15 | 24 weeks | Change in Geriatric Depression Scale-15 scores, Score range 0-15 with higher scores indicating worse outcomes. |
| Fatigue Severity Scale | 24 weeks | Change in Fatigue Severity Scale scores, Score range 9-63 with higher scores indicating worse outcomes. |
| Insomnia Severity Index | 24 weeks | Change in Insomnia Severity Index, Score range 0-28 with higher scores indicating worse outcomes. |
| Parkinson's Disease Questionnaire-8 | 24 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORThomas Guttuso, MD
University at Buffalo
Outcome results
None listed