Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia
Condition: Frontotemporal Dementia (FTD)
MeSH terms: Dementia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Behavioral Symptoms
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Behavioral symptoms of Frontotemporal dementia (FTD), including agitation, aggression, and
      inappropriate repetitive behaviors are common, distressing to patients and caregivers, often
      lead to institutionalization, and can be very difficult and expensive to treat. There is a
      dearth of medication for treating these symptoms in FTD. Typically, antidepressants and
      antipsychotic medications are prescribed - which low efficacy and, with the latter class,
      carry serious adverse effects such as parkinsonism and increased cardiovascular-related
      mortality. The investigators propose a study of the efficacy of lithium carbonate compared to
      placebo in the treatment of agitation, aggression, and inappropriate repetitive behaviors in
      60 patients with FTD in a randomized, double-blind, two-arm parallel 12-week trial. Lithium
      is a highly effective treatment for mania and symptoms of agitation or aggression in bipolar
      disorder. It also inhibits tau aggregation and phosphorylation, leading to considerable
      interest in its use as a disease-modifying treatment for tauopathies such as FTD and
      Alzheimer's disease. Unfortunately, earlier trials using typical doses (i.e., doses
      prescribed for treatment of bipolar disorder) showed high incidence of serious adverse
      effects (including confusion and delirium). For this proposed study the investigators will:
      1) use lower doses and lower target serum concentrations than have preceding trials (shown in
      preliminary data from a Columbia study and data from other labs to be well-tolerated) and 2)
      target behavioral symptoms rather than cognitive outcomes.
    

Intervention name(s): Lithium Carbonate; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): Lithobid
Intervention MeSH terms: Lithium Carbonate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Lithium; Lithium Carbonate