Effects of Lithium Therapy on Blood-based Therapeutic Targets in Parkinson's Disease.

NCT04273932 | Completed Phase 1 FDA Drug

• 1 other identifier: STUDY00003688
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine if one of three low doses of lithium therapy for 6 months can engage one or more blood-based therapeutic targets implicated in Parkinson's disease (PD) pathophysiology. Results of this study will help to determine if lithium therapy is worthwhile to further investigate as a potential disease-modifying therapy in PD, the optimal dose to study and the optimal PD subgroup most likely to benefit from lithium therapy.

Conditions

Parkinson Disease

Keywords

Lithium; Alpha-synuclein

Outcome Measures

Primary Outcomes (5)

• Plasma alpha-synuclein assessed by ultra-sensitive, immunomagnetic reduction assay (MagQu, LLC, Surprise, AZ).

  Change from baseline to 24 weeks

• Peripheral blood mononuclear cell (PBMC) Nurr1 mRNA levels by real-time polymerase chain reaction.

  Change from baseline to 24 weeks

• PBMC phosphorylated (p) and total (t) levels of pSerine9 and t-glycogen synthase kinase-3B

  Change from baseline to 24 weeks

• Plasma brain-derived neurotrophic factor (BDNF).

  Change from baseline to 24 weeks

• PBMC pThreonine308 and t-protein kinase B (Akt).

  Change from baseline to 24 weeks

Secondary Outcomes (9)

• Trough, steady-state plasma lithium levels by ICP/MS

  Change from baseline to 24 weeks

• Patient tolerability

  Up to 24 weeks

• Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III (Motor Examination) and question 1.11 (Constipation Problems) in the "on" state

  Change from baseline to weeks 12 and 24.

• Parkinson's Anxiety Scale

  Change from baseline to weeks 12 and 24.

• Geriatric Depression Scale-15

  Change from baseline to weeks 12 and 24.

Study Arms (4)

Lithium aspartate 15mg a day

EXPERIMENTAL

15mg of elemental lithium administered every morning by mouth.

Drug: Lithium

Lithium aspartate 45mg a day

EXPERIMENTAL

20mg every morning and 25mg every evening of elemental lithium administered by mouth.

Drug: Lithium

Lithium carbonate

EXPERIMENTAL

The dose will be titrated based on weekly blood tests to achieve a target serum level of 0.40-0.50mmol/L, which represents an elemental lithium dose of about 85-170mg a day.

Drug: Lithium

No lithium treatment

NO INTERVENTION

Control arm

Interventions

Lithium DRUG

Lithium aspartate of lithium carbonate will be administered by mouth.

Lithium aspartate 15mg a day; Lithium aspartate 45mg a day; Lithium carbonate

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

1. Diagnosed with PD according to the UK Brain Bank Criteria. 2. 45-80yo. 3. Clinical Dementia Rating Scale score of 0 or 0.5. 4. Stable PD medications for previous 30 days and no current need for changes in the opinion of the PI. 5. No formed visual hallucinations or delusions for previous year. 6. Never taken prescription or over-the-counter lithium. 7. Stable or no diuretics for past 4 weeks and no need for changes for at least 6 months, in the PI's opinion. 8. Stable doses of antidepressants, antihypertensives and non-steroidal anti-inflammatory medications (NSAIDs) for previous 60 days and no current need to adjust such medications. 9. No history of cardiac arrhythmias besides atrial fibrillation that is rate controlled. 10. No unstable cardiac, medical or psychiatric condition in the opinion of the PI. 11. No current use of illicit drugs or current alcohol abuse in the opinion of the PI. 12. No history of hypothyroidism, not receiving thyroid replacement therapy and normal thyroid stimulating hormone (TSH) level at screening visit. 13. Estimated renal glomerular filtration rate ≥50 at screening visit. 14. No history of receiving or planning to receive nilotinib or a glucagon-like peptide-1 agonist medication such as exenatide. 15. No use of tobacco products for the previous year. 16. No deep brain stimulation (DBS) or possible need for DBS for at least 1-year in the opinion of the PI. 17. 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. 18. Not enrolled in another clinical trial. 19. Willing and able to sign informed consent and follow study procedures.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• State University of New York at Buffalo: lead

Study Sites (1)

University at Buffalo

Williamsville, New York, 14221, United States

Location

Related Publications (1)

• Guttuso T Jr, Shepherd R, Frick L, Feltri ML, Frerichs V, Ramanathan M, Zivadinov R, Bergsland N. Lithium's effects on therapeutic targets and MRI biomarkers in Parkinson's disease: A pilot clinical trial. IBRO Neurosci Rep. 2023 May 7;14:429-434. doi: 10.1016/j.ibneur.2023.05.001. eCollection 2023 Jun.

  PMID: 37215748 RESULT

Related Links

• PubMed Link to study results

MeSH Terms

Conditions

Parkinson Disease; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

Lithium

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Model Details: Randomized, parallel group, open-label trial

Study Record Dates

• First Submitted: October 31, 2019
• First Posted: February 18, 2020
• Study Start: October 17, 2019
• Primary Completion: June 15, 2023
• Study Completion: August 12, 2023
• Last Updated: August 15, 2023

Record last verified: 2023-08

Locations

US (1)