Lithium for Parkinson's Disease

Overseen By Thomas Guttuso, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: State University of New York at Buffalo

Disqualifiers: Thyroid, Renal, Brain surgery, others

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether daily lithium intake can affect Parkinson's disease by examining brain scans and blood tests. Researchers aim to determine if lithium causes changes compared to a placebo (a pill with no active medicine). The trial includes individuals diagnosed with Parkinson's disease for less than four years, who have not used lithium before, and who do not smoke or use THC products. As a Phase 1/Phase 2 trial, this research seeks to understand how lithium works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to early-stage treatment insights.

Will I have to stop taking my current medications?

The trial requires that your Parkinson's disease medications have been stable for over 30 days and your psychiatric and diuretic medications have been stable for over 60 days, with no expected changes for at least 24 weeks. If your medications meet these criteria, you won't need to stop taking them.

Is there any evidence suggesting that lithium is likely to be safe for humans?

Research has shown that lithium might protect brain cells. Some studies suggest it could benefit diseases like Parkinson's. However, lithium can also cause side effects, such as shaking and symptoms similar to Parkinson's, especially at higher doses. Therefore, treatment requires careful monitoring.

Earlier studies found that low doses of lithium helped prevent movement problems in animals, suggesting that lower doses might be easier for the body to handle. The current trial tests a low dose of 20mg per day. Although this dose is lower, side effects remain possible, so participants will be closely monitored for safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Parkinson's disease?

Unlike the standard treatments for Parkinson's Disease, which often focus on managing symptoms through dopamine replacement or modulation, lithium offers a potential new avenue by acting on neuroprotective pathways. Researchers are excited about lithium because it has a unique ability to stabilize mood and protect brain cells, which might slow the progression of the disease rather than just addressing symptoms. This approach could lead to better long-term outcomes for patients by targeting the underlying disease mechanisms. Additionally, lithium's long history of use in other conditions provides a substantial safety profile, making it a promising candidate for repurposing in Parkinson's Disease.

What evidence suggests that lithium might be an effective treatment for Parkinson's disease?

Research has shown that lithium, which participants in this trial may receive, might slow the progression of Parkinson's disease. Studies have found that a low dose of lithium can prevent movement problems and damage in brain areas affected by Parkinson's. It also protects brain cells from harm. Additionally, lithium reduces harmful proteins in the brain, such as amyloid-β and tau, which are linked to various brain diseases. These findings suggest that lithium could help manage symptoms and slow the disease in people with Parkinson's. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for early-stage Parkinson's disease patients who haven't used lithium before and have no other neurological conditions. Participants should not be tobacco or THC users, must have stable PD medications for over a month, and cannot have any active medical issues that could affect the study.

Inclusion Criteria

Have no history of brain imaging findings suggesting another neurological condition besides PD

Have no active medical or psychiatric condition that may interfere with study procedures in the investigator's opinion

My thyroid and kidney functions are normal.

Exclusion Criteria

Have use of tobacco or THC products within the past year

Have active medical or psychiatric condition that may interfere with study procedures in the investigator's opinion

I have had Parkinson's disease for more than 4 years or I do not have Parkinson's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either lithium 20mg/day or placebo for 24 weeks

24 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lithium

Trial Overview The study is testing if a low dose of lithium (20mg/day) can impact MRI and blood biomarkers in Parkinson's disease compared to a placebo. It involves 20 participants with early-stage PD to see if there are any benefits.

How Is the Trial Designed?

Group I: Lithium Active Control 1 Intervention

Lithium: 10mg, 2x/day

Group II: Placebo Placebo Group 1 Intervention

Identical capsules filled with cellulose: 10mg, 2x/day

Lithium is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Lithium for:

• Bipolar disorder
• Manic episodes
• Major depressive disorder

Approved in United States as Lithium for:

• Bipolar disorder
• Manic episodes

Approved in Canada as Lithium for:

• Bipolar disorder
• Manic episodes
• Major depressive disorder

Approved in Japan as Lithium for:

• Bipolar disorder
• Manic episodes

Who Is Running the Clinical Trial?

State University of New York at Buffalo

Lead Sponsor

Trials

279

Recruited

52,600+

The Cure Parkinson's Trust

Collaborator

Trials

3

Recruited

110+

Cure Parkinson's

Collaborator

Trials

6

Recruited

5,200+

Published Research Related to This Trial

In a study using male Wistar rats with brain cholinergic lesions induced by ibotenic acid, lithium treatment significantly reduced behavioral deficits and improved choline acetyltransferase activity in the affected cortex.

The results suggest that lithium may offer protective effects against neurotoxicity caused by excitatory amino acids, indicating its potential therapeutic role in similar neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A protective effect of lithium on rat behaviour altered by ibotenic acid lesions of the basal forebrain cholinergic system. Pascual, T., Gonzalez, JL.[2019]

Lithium cholesterol sulfate (LiCS) was found to be more effective than lithium chloride (LiCl) in enhancing the phosphorylation of GSK3β, a key marker in neurodegenerative diseases, at significantly lower concentrations, suggesting it may have a better safety profile.

LiCS also effectively reduced tau phosphorylation in cell models, which is important for Alzheimer's disease, while LiCl did not show this effect, indicating that LiCS could be a promising new treatment option for Alzheimer's and Autism Spectrum Disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lithium Cholesterol Sulfate: A Novel and Potential Drug for Treating Alzheimer's Disease and Autism Spectrum Disorder. Hu, W., Zhao, M., Lian, J., et al.[2022]

In a study involving 20 patients with Parkinson's disease, lisuride was well-tolerated at doses up to 5 mg daily, showing significant improvements in symptoms like akinesia, rigidity, and tremor.

While lisuride had similar side effects to other Parkinson's treatments like levodopa and bromocriptine, it was associated with a higher incidence of somnolence (drowsiness).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisuride in parkinsonism. Gopinathan, G., Teräväinen, H., Dambrosia, JM., et al.[2019]

A case study of an elderly female revealed that lithium carbonate can cause disabling parkinsonism as a side effect, even without other signs of lithium toxicity.

The patient's neurological symptoms completely resolved after stopping lithium, and mild Parkinson's symptoms returned when lithium was resumed at higher serum levels, suggesting that older age and higher lithium levels may increase the risk of this side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disabling parkinsonism due to lithium: a case report. Holroyd, S., Smith, D.[2017]

In a study of 63 patients with advanced Parkinson's disease treated with levodopa-carbidopa intestinal gel (LCIG) for an average of 19 months, 90% experienced at least one adverse event (AE), primarily related to the PEG-J tube or gastrointestinal issues.

Despite the high incidence of AEs, 84.4% of patients reported an improvement in their condition, indicating that LCIG can provide significant clinical benefits even with the risk of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of levodopa-carbidopa intestinal gel for advanced Parkinson's disease: A large single-center study. Blaise, AS., Baille, G., Carrière, N., et al.[2021]

Carbidopa/levodopa enteral suspension (CLES) is a cost-effective treatment for advanced Parkinson's disease, providing an incremental gain of 4.61 quality-adjusted life years (QALY) compared to standard care, with a cost-effectiveness ratio of $7711 per QALY.

The analysis was based on a Markov model using real-world data, indicating that CLES offers significant benefits in managing severe motor fluctuations in patients with advanced Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Carbidopa-Levodopa Enteral Suspension for Advanced Parkinson's Disease in the United States. Pahwa, R., Merola, A., Soileau, M., et al.[2023]

In a study involving 26 participants, the liquid formulation of levodopa carbidopa ascorbic acid solution (LCAS) significantly improved motor function compared to traditional tablet formulations, as measured by the Timed Up and Go Test (TUG).

LCAS showed similar efficacy to Duodopa jejunal infusion in managing motor fluctuations in advanced Parkinson's disease, indicating it is a viable and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Liquid Sinemet in Routine Clinical Practice of Advanced Parkinson's Disease: A Comparison of Available Options. Sung, CB., Danoudis, M., Paul, E., et al.[2023]

In a study of 23 patients on lithium carbonate for an average of 43 months, it was found that they experienced a significantly lower peak frequency of postural tremor compared to matched control subjects, suggesting a unique tremor profile associated with lithium use.

The patients on lithium also exhibited significantly greater extrapyramidal symptoms, indicating that these symptoms are common long-term side effects of lithium carbonate therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiological characteristics of tremor after chronic lithium therapy. Tyrer, P., Lee, I., Trotter, C.[2019]

In a study involving 10 patients with severe Parkinsonism, lisuride was successfully used to completely replace bromocriptine in all cases, demonstrating its potential as an effective alternative treatment.

Lisuride has similar antiparkinsonian effects to bromocriptine and levodopa, but its short duration of action and common side effects highlight the need for careful management, although it may be particularly useful in emergency situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisuride in the treatment of Parkinsonism. Schachter, M., Sheehy, MP., Parkes, JD., et al.[2019]

Lithium ascorbate, an organic lithium salt, shows promise as a neuroprotective agent, demonstrating greater effectiveness in supporting neuronal survival under stress compared to traditional inorganic lithium salts like lithium chloride or carbonate.

With an extremely low toxicity profile (LD50 > 5000 mg/kg) and the ability to reduce brain damage and preserve myelin sheaths in models of alcohol intoxication, lithium ascorbate could be a safer alternative for neuropharmacological applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lithium Ascorbate as a Promising Neuroprotector: Fundamental and Experimental Studies of an Organic Lithium Salt. Torshin, IY., Gromova, OA., Ostrenko, KS., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4621308/

Potential application of lithium in Parkinson's and other ... Nonetheless, the investigators believe their results show that lithium may slow the disease progression from cognitive impairment to dementia (Forlenza et al., ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1568163724000497

Lithium and disease modification: A systematic review ... Our analysis showed that lithium treatment has neuroprotective effects in diseases. Lithium treatment reduced amyloid-β and tau levels and significantly ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4254598/

Lithium prevents parkinsonian behavioral and striatal ... The results of our study show that low-dose lithium can prevent parkin-induced motor impairment and striatal degeneration. Furthermore, parkin-related glial ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02862210

Study Details | NCT02862210 | Low-Dose Lithium for the ... Lithium is a highly effective treatment for mania and symptoms of agitation or aggression in bipolar disorder. It also inhibits tau aggregation and ...

5. researchgate.net researchgate.net/publication/378247554_Lithium_and_Disease_Modification_A_Systematic_Review_and_Meta-analysis_in_Alzheimer's_and_Parkinson's_Disease

Lithium and Disease Modification: A Systematic Review ... Our analysis showed that lithium treatment has neuroprotective effects in diseases. Lithium treatment reduced amyloid-β and tau levels and significantly ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0041008X25002352

Preclinical pharmacokinetic and toxicokinetic profiles of AY ... Pharmacokinetic data demonstrated that AY-1001 has a faster onset of action, a shorter half-life, and a higher blood-brain barrier transmission rate, compared ...

7. withpower.com withpower.com/trial/phase-2-parkinson-disease-5-2024-63ee4

Lithium for Parkinson's Disease · Info for Participants However, lithium can cause side effects like tremors and parkinsonism, especially at higher doses, which requires careful monitoring.