Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia

NCT02862210 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: NYSPI 7310
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Frontotemporal dementia (FTD) is a progressive neurodegenerative illness that affects the frontal and anterior temporal lobes of the brain. Changes in behavior, including agitation, aggression, and repetitive behaviors, are common symptoms in FTD. The investigators currently do not have good medications to treat these symptoms in FTD, and the medications the investigators use often have side effects. In this project, the investigators will test the use of low-dose lithium, compared to a placebo pill, for the treatment of behavioral symptoms in FTD. Lithium greatly reduces the behavioral symptoms of bipolar disorder, and many have found low-dose lithium to be well-tolerated in patients with dementia. Lithium appears to inhibit the creation of a protein involved in many cases of FTD called tau.

Conditions

Frontotemporal Dementia (FTD)

Keywords

Lithium; Lithium Carbonate

Outcome Measures

Primary Outcomes (1)

• Change in Agitation and Aggression as Measured by the Neuropsychiatric Inventory Scale (NPI)

  The NPI is a scale designed to assess behavioral changes due to neurological illness. It uses a standardized caregiver interview to rate patient symptoms in a variety of domains, including "Agitation/Aggression." Each domain includes a number of questions about potential specific symptoms, and then asks the caregiver to rate symptom frequency (1, occasionally, to 4, very frequently) as well as symptom severity (1, mild, to 3, severe). Scores range from from 0-12, with 0 being no symptoms and 12 being very frequent and severe symptoms. The study aims to test the effect of lithium on agitation/aggression as compared to placebo by testing whether participants taking lithium show a greater reduction in their NPI "Agitation/Aggression" domain score over the course of the trial.

  12 weeks

Secondary Outcomes (1)

• Number of Responders in the Lithium and Placebo Groups

  12 weeks

Other Outcomes (4)

• Change in Motor Symptoms as Measured by the NPI

  12 weeks

• Presence of Adverse Events as Measured by the Treatment Emergent Symptoms Scale (TESS)

  12 weeks

• The Relationship Between Changes in Brain-derived Neurotropic Factor (BDNF) Serum Levels and Changes in NPI "Agitation/Aggression" Score

  Baseline and 12 weeks

Study Arms (2)

Lithium carbonate

EXPERIMENTAL

Lithium will be prescribed starting at 150 mg/day, with subsequent dose titration to 300, 450, and 600 mg/day as tolerated according to side effects and blood lithium level.

Drug: Lithium Carbonate

Placebo

PLACEBO COMPARATOR

Placebo will be prescribed starting at 1 pill per day, with subsequent dose titration to 2,3, and 4 pills per day as tolerated by sham blood lithium levels provided by an unblinded study team member.

Drug: Placebo

Interventions

Lithium Carbonate DRUG

Lithium will be prescribed starting at 150 mg/day, with subsequent dose titration to 300, 450, and 600 mg/day as tolerated according to side effects and blood lithium level.

Also known as: Lithobid

Lithium carbonate

Placebo DRUG

Placebo will be prescribed starting at 1 pill per day, with subsequent dose titration to 2,3, and 4 pills per day as tolerated by sham blood lithium levels.

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 40-85
• A diagnosis of behavioral variant FTD (bv-FTD) or semantic variant Primary Progressive Aphasia (sv-PPA, which is generally accompanied by a behavioral syndrome), or agrammatic/non-fluent Primary Progressive Aphasia (nfv-PPA) with behavioral symptoms
• Neuropsychiatric Inventory (NPI) agitation/aggression subscale score ≥4 or disinhibition subscale score ≥ 4 or repetitive behavior subscale ≥ 4 or total score ≥ 6. On each subscale, a score higher than 4 represents moderate to severe symptoms
• Folstein Mini-Mental State Examination (MMSE) score 5-26/30
• An study partner (usually a family member) is required to provide information during interviews about the patient
• Capacity to consent. Subjects without capacity to consent must have capacity to appoint a surrogate
• Structural MRI or CT scan after symptom onset

You may not qualify if:

• The diagnosis of bipolar disorder or schizophrenia or schizoaffective disorder
• Alcohol or substance use disorder in the prior 6 months
• Current diagnosis of other major neurological disorder, e.g., Alzheimer's Disease (AD), stroke with residual clinical deficits, multiple sclerosis, Parkinson's disease. Subjects with MRI or CT evidence of cerebrovascular disease but without clinical signs of stroke will be included
• Sitting blood pressure \> 150/90 mm Hg, unstable cardiac disease, severe or unstable medical illness
• Use of medications, including diuretics, known to have adverse effects when combined with lithium. Use of antipsychotic medications will be permitted
• Current major depression or suicidality or dangerous behavior with risk of harm to self and others
• Corrected QT interval (QTc) interval \> 460 ms at the time of baseline electrocardiogram (EKG)
• Woman of child-bearing potential

Sponsors & Collaborators

• Columbia University: lead
• Alzheimer's Drug Discovery Foundation: collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Frontotemporal Dementia

Interventions

Lithium Carbonate

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Results Point of Contact

• Title: Edward Huey, MD
• Organization: Brown University

edward_huey@brown.edu

401-455-6403

Study Officials

• Edward Huey, MD

  Brown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Study Record Dates

• First Submitted: August 7, 2016
• First Posted: August 10, 2016
• Study Start: January 27, 2017
• Primary Completion: November 20, 2022
• Study Completion: November 20, 2022
• Last Updated: February 3, 2025
• Results First Posted: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)