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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2017 by Columbia University
Sponsor:
Collaborator:
Alzheimer’s Drug Discovery Foundation
Information provided by (Responsible Party):
Edward D Huey, MD, Columbia University
ClinicalTrials.gov Identifier:
NCT02862210
First received: August 7, 2016
Last updated: January 5, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention Phase
Frontotemporal Dementia (FTD)
Drug: Lithium Carbonate
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Reduction in agitation as measured by the NPI scale [ Time Frame: 12 weeks ]
  • Reduction in aggression as measured by the NPI scale [ Time Frame: 12 weeks ]

Secondary Outcome Measures:
  • Number of adverse events [ Time Frame: 12 weeks ]

Estimated Enrollment: 60
Study Start Date: December 2016
Estimated Study Completion Date: March 2020
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lithium carbonate
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
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.
Other Name: Lithobid
Placebo Comparator: Placebo
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
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.

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 the study 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.
  Eligibility

Ages Eligible for Study:   40 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 < 44 ml/min/1.73m2 will also lead to exclusion
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02862210

Contacts
Contact: Edward Huey, MD 212-305-1134 edh2126@columbia.edu

Locations
United States, Maryland
Johns Hopkins University Not yet recruiting
Baltimore, Maryland, United States, 21205
Contact: Sarah Lawrence, MD    410-550-9020    swoody1@jhmi.edu   
Principal Investigator: Chiadi Onyike, MD         
Sponsors and Collaborators
Columbia University
Alzheimer’s Drug Discovery Foundation
Investigators
Principal Investigator: Edward Huey, MD Columbia University
  More Information

Responsible Party: Edward D Huey, MD, Assistant Professor of Psychiatry, Columbia University
ClinicalTrials.gov Identifier: NCT02862210     History of Changes
Other Study ID Numbers: NYSPI 7310 
Study First Received: August 7, 2016
Last Updated: January 5, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Columbia University:
Lithium
Lithium Carbonate

Additional relevant MeSH terms:
Dementia
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Behavioral Symptoms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Lithium Carbonate
Antidepressive Agents
Psychotropic Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants

ClinicalTrials.gov processed this record on February 23, 2017