Phase 2
N=16
Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia
Frontotemporal Dementia (FTD)
Bottom Line
View on ClinicalTrials.gov: NCT02862210 ↗Enrolled (actual)
16
Serious AEs
12.5%
Results posted
Feb 2025
Primary outcome: Primary: Change in Agitation and Aggression as Measured by the Neuropsychiatric Inventory Scale (NPI) — 7.14; 5.75 score on a scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Lithium Carbonate (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- Columbia University
- Primary completion
- Nov 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Agitation and Aggression as Measured by the Neuropsychiatric Inventory Scale (NPI) |
7.14; 5.75 | — |
| SECONDARY Number of Responders in the Lithium and Placebo Groups |
0; 0 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- Medical contraindication or history of intolerability to lithium, falls in the last month, current abnormal thyroid functions (T3, T4 or thyroid stimulating hormone (TSH); treated hypothyroidism with normal thyroid function tests will not lead to exclusion), creatinine level > 1.5 mg/100 ml or glomerular filtration rate 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
Data sourced from ClinicalTrials.gov (NCT02862210). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.