Lithium for Mild Cognitive Impairment

(LATTICE Trial)

Overseen By James Emanuel

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ariel Gildengers, MD

Disqualifiers: Major psychiatric, neurologic illness, others

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether lithium can help slow down or delay Alzheimer's disease in older adults with mild cognitive impairment. Lithium is believed to support brain health by encouraging new brain cell growth, protecting existing cells, and reducing harmful proteins. The study will compare the effects of lithium over time to see if it helps maintain memory and cognitive function. Lithium has been studied for its potential to slow cognitive decline and modify Alzheimer's disease pathology, with some studies showing it may block harmful proteins and support brain health.

Do I need to stop my current medications for the trial?

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

Is lithium safe for human use?

Lithium, commonly used for bipolar disorder, has a narrow therapeutic window, meaning the difference between a helpful dose and a harmful one is small, requiring careful monitoring to avoid serious side effects. Newer forms like lithium ascorbate and LISPRO show promise with potentially lower toxicity and improved safety profiles in animal studies, but traditional lithium salts can have significant side effects. ^{1 2 3 4 5}

How does the drug lithium carbonate differ from other treatments for mild cognitive impairment?

Lithium carbonate is unique because it has been shown to potentially improve cognitive decline by reducing neuroinflammation and inactivating certain enzymes in the brain, which is different from other treatments that may not target these specific mechanisms. ^{1 5 6 7 8}

Research Team

Ariel Gildengers, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for people aged 60 or older who have been diagnosed with mild cognitive impairment. It's not suitable for those with conditions that make lithium use unsafe, like kidney problems, major neurological diseases like multiple sclerosis, serious psychiatric issues, or if they can't do certain mental tests due to permanent disabilities.

Exclusion Criteria

Major psychiatric illness (mild psychiatric illness may be included)

I do not have a major neurological illness like multiple sclerosis.

I cannot take lithium due to kidney problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lithium or placebo for 2 years with quarterly monitoring

104 weeks

Quarterly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Lithium Carbonate
• Placebo oral capsule

Trial Overview The study is testing whether lithium carbonate can prevent or slow down memory loss and decline in brain function in older adults at risk of dementia compared to a placebo (a pill without medication). Participants will be randomly assigned to receive either lithium or the placebo.

Participant Groups

Group I: Lithium carbonate Experimental Treatment 1 Intervention

Lithium carbonate will be initiated at 150 mg per day and increased based on blood levels until a steady blood level between 0.6 and 0.8 meq/L is achieved. Participants will continue at the dose achieved for 2 years with quarterly monitoring.

Group II: placebo Placebo Group 1 Intervention

Matching placebo will be initiated and increased based on pretend blood levels. Participants will take placebo for 2 years with quarterly monitoring.

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

Approved in European Union as Lithium Carbonate for:

• Bipolar disorder

Approved in United States as Lithium Carbonate for:

• Bipolar disorder

Approved in Canada as Lithium Carbonate for:

• Bipolar disorder

Approved in Japan as Lithium Carbonate for:

• Bipolar disorder

Who Is Running the Clinical Trial?

Ariel Gildengers, MD

Lead Sponsor

Trials

1

Recruited

80+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

Lithium is considered effective for preventing relapses in bipolar disorder and reducing suicide risk, but its efficacy for treating acute episodes is not as strong as often claimed, with only a minority of patients experiencing significant benefits.

Despite its limitations, lithium remains a crucial treatment option for bipolar disorder, and its under-utilization in North America is more based on opinion than on the evidence supporting its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lithium - a continuing story in the treatment of bipolar disorder. Carney, SM., Goodwin, GM.[2022]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

LISPRO mitigates β-amyloid and associated pathologies in Alzheimer's mice. [2022]

2. Denmark pubmed.ncbi.nlm.nih.gov

Lithium - a continuing story in the treatment of bipolar disorder. [2022]

3. 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]

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

Association Between Lithium Use and Risk of Alzheimer's Disease. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

6. Netherlands pubmed.ncbi.nlm.nih.gov

Lithium as a Treatment for Alzheimer's Disease: A Systematic Review and Meta-Analysis. [2018]

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

Effects of lithium carbonate on memory and other cognitive functions. [2013]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Effects of Chronic and Acute Lithium Treatment on the Long-term Potentiation and Spatial Memory in Adult Rats. [2022]