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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how lithium affects brain scans and blood tests in people with Parkinson's disease, focusing on those who have completed a previous lithium study. Researchers seek to understand how lithium might aid Parkinson's treatment. It suits individuals who have finished a specific study at the University at Buffalo and have Parkinson’s without unstable medical conditions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking insights.

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

Research has shown that lithium, when taken in certain amounts, is generally well-tolerated by patients. Studies have found that lithium treatments, including lithium aspartate, are usually safe at the tested doses. In these studies, patients did not experience major side effects from the treatment.

Although lithium is not commonly used for Parkinson's disease yet, it has been tested for other health issues, suggesting it can be safe when monitored correctly.

In Parkinson's trials, researchers administer lithium in low doses (0.25-0.50 mmol/L). This careful dosing aims to reduce any possible side effects while still providing potential benefits. Overall, lithium appears to have a good safety record when used at these tested doses. ^{1 2 3 4 5}

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

Researchers are excited about lithium aspartate for Parkinson's disease because it offers a unique approach compared to standard treatments like levodopa and dopamine agonists. Unlike these treatments, which mainly focus on replenishing dopamine or stimulating dopamine receptors, lithium aspartate targets neuroprotective pathways, potentially slowing the progression of the disease. Additionally, the low-dose strategy aims to minimize side effects, offering a promising alternative for patients who struggle with the adverse effects of current medications.

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

This trial will evaluate the effects of lithium aspartate on Parkinson's disease. Research has shown that lithium might help with Parkinson's disease. In previous studies, medium doses of lithium aspartate led to positive changes in blood tests and MRI scans in people with Parkinson's. Observational research found that small daily doses of lithium seemed to reduce the risk of developing Parkinson's by 77%. Early lab studies also suggested that low doses of lithium might protect brain cells typically lost in Parkinson's. Overall, these findings suggest lithium could be promising for treating Parkinson's. ^{2 6 7 8 9}

Who Is on the Research Team?

Thomas Guttuso, MD

Principal Investigator

University at Buffalo

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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]

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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37215748/

Lithium's effects on therapeutic targets and MRI biomarkers ... Medium-dose lithium aspartate therapy was associated with engagement of blood-based therapeutic targets and improvements in MRI disease-progression biomarkers.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06592014

Study Details | NCT06592014 | Lithium for Parkinson's In observational studies, small daily doses of lithium from smoking cigarettes have been associated with a 77% reduced risk of developing Parkinson's disease ( ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10227915/

Beyond its Psychiatric Use: The Benefits of Low-dose Lithium ... Currently, literature shows that low-dose lithium (≤0.5 mM) may be beneficial for cardiovascular, musculoskeletal, metabolic, and cognitive function, as well as ...

4. cureparkinsons.org.uk cureparkinsons.org.uk/2024/05/phase-1-clinical-trial-of-lithium-in-parkinsons-set-to-begin/

Clinical trial of lithium in Parkinson's set to begin Early laboratory research suggests that lithium at very low doses may help protect against the loss of dopamine nerve cells (neurons) seen in Parkinson's. In ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06099886

Repurposing Lithium for Parkinson's Disease In observational studies, small daily doses of lithium have been associated with a 77% reduced risk of developing Parkinson's disease (PD).

6. 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., ...

7. withpower.com withpower.com/trial/lithium-for-parkinsons-disease-4e47e

Lithium for Parkinson's Disease · Info for Participants 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 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10196787/

Lithium's effects on therapeutic targets and MRI biomarkers ... Medium-dose lithium aspartate therapy was associated with engagement of blood-based therapeutic targets and improvements in MRI disease-progression biomarkers.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1064748125004968

Efficacy and Safety of Lithium for Behavioral and Cognitive ... Lithium demonstrated an acceptable safety profile within the dosing regimens studied. However, current evidence does not support consistent ...