Lithium for Parkinson's Disease

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: State University of New York at Buffalo

Must be taking: Lithium

Disqualifiers: Unstable cardiac, Neurologic, Psychiatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

35 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is lithium generally safe for humans?

Research on lithium in animals suggests it may protect against certain brain injuries, but this doesn't directly address its safety in humans. More specific human studies are needed to confirm its safety. ^{1 2 3 4 5}

How does the drug lithium differ from other treatments for Parkinson's disease?

Lithium, particularly in the form of lithium ascorbate, may offer neuroprotective benefits by supporting neuron survival and reducing brain damage, which is different from traditional Parkinson's treatments that primarily focus on managing motor symptoms. However, lithium can cause side effects like tremors and parkinsonism, especially at higher doses, which requires careful monitoring. ^{6 7 8 9 10}

What is the purpose of this trial?

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.

Research Team

Thomas Guttuso, MD

Principal Investigator

University at Buffalo

Eligibility Criteria

This trial is for Parkinson's disease patients who have already completed a 24-week lithium clinical trial. It aims to further investigate the effects of lithium therapy on certain biomarkers.

Inclusion Criteria

All PD patients completing STUDY00007253 or STUDY00008239 at the University at Buffalo will be eligible

Exclusion Criteria

Willing and able to sign informed consent and follow study procedures

I am not pregnant, not nursing, and use contraception.

No unstable cardiac, medical, neurologic or psychiatric condition in the opinion of the PI

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lithium therapy with dosage adjusted to achieve a serum lithium level of 0.25-0.50mmol/L for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive lithium therapy to maintain target serum lithium levels for an additional 24 weeks

24 weeks

Treatment Details

Interventions

• Lithium

Trial Overview The study tests the impact of a 24-week course of lithium aspartate, aiming for specific low serum levels, on MRI and blood-based markers in Parkinson's patients.

Participant Groups

Group I: Lithium aspartate Experimental Treatment 1 Intervention

Lithium aspartate with dosage adjusted to achieve a serum lithium level of 0.25-0.50mmol/L

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Lisuride in parkinsonism. [2019]

3. Denmark pubmed.ncbi.nlm.nih.gov

Lisuride in the treatment of Parkinsonism. [2019]

4. France pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of levodopa-carbidopa intestinal gel for advanced Parkinson's disease: A large single-center study. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Carbidopa-Levodopa Enteral Suspension for Advanced Parkinson's Disease in the United States. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Lithium Ascorbate as a Promising Neuroprotector: Fundamental and Experimental Studies of an Organic Lithium Salt. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

The Use of Liquid Sinemet in Routine Clinical Practice of Advanced Parkinson's Disease: A Comparison of Available Options. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Physiological characteristics of tremor after chronic lithium therapy. [2019]

9. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Lithium Cholesterol Sulfate: A Novel and Potential Drug for Treating Alzheimer's Disease and Autism Spectrum Disorder. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Disabling parkinsonism due to lithium: a case report. [2017]