Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia (Lithium)
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ClinicalTrials.gov Identifier: NCT02862210 |
Recruitment Status :
Recruiting
First Posted : August 10, 2016
Last Update Posted : October 8, 2021
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Condition or disease | Intervention/treatment | Phase |
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Frontotemporal Dementia (FTD) | Drug: Lithium Carbonate Drug: Placebo | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 60 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia |
Actual Study Start Date : | January 27, 2017 |
Estimated Primary Completion Date : | September 2022 |
Estimated Study Completion Date : | March 2023 |

Arm | Intervention/treatment |
---|---|
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.
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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.
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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. |
- Change in agitation and aggression as measured by the Neuropsychiatric Inventory Scale (NPI) [ Time Frame: 12 weeks ]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). Thus, in each domain a patient can score from 0-12, with 0 being no symptoms and 12 being very frequent and severe symptoms. The study aims to test that lithium will significantly reduce 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.
- Proportion of responders in the lithium and placebo groups [ Time Frame: 12 weeks ]Response requires a 30% decrease in NPI core score (sum of domain scores for "Agitation/Aggression" and "Aberrant Motor Behavior") plus a Clinical Global Impression (CGI) Change score of much improved or very much improved (CGI based on these behavioral symptoms only).
- Change in motor symptoms as measured by the NPI [ Time Frame: 12 weeks ]NPI domain "Aberrant Motor Behaviors" will be observed to test that lithium will significantly reduce repetitive behaviors as compared to placebo, by examining whether participants taking lithium show a greater reduction in their "Aberrant Motor Behaviors" NPI domain score.
- Presence of adverse events as measured by the Treatment Emergent Symptoms Scale (TESS) [ Time Frame: 12 weeks ]The tolerability of low-dose lithium by assessing emergent side effects over the course of the 12-week trial will be assessed. The side effects will be captured with TESS in which 30 symptoms are rated either "Absent," "Mild," "Moderate," or "Severe." The change in TESS score from baseline to week 12 will be observed.
- The relationship between changes in brain-derived neurotropic factor (BDNF) serum levels and changes in NPI "Agitation/Aggression" score and "Aberrant Motor Behavior" score [ Time Frame: 12 weeks ]The baseline serum BDNF levels as a potential baseline predictor of lithium treatment response and an increase from pre to post-treatment BDNF levels as a potential biomarker correlate of improvement in symptoms (as measured by the NPI) will be explored.

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Ages Eligible for Study: | 40 Years to 85 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02862210
Contact: Colin Stein | 212-304-7943 | cs4125@cumc.columbia.edu | |
Contact: Edward D. Huey, MD | 212-305-1134 | edh2126@columbia.edu |
United States, New York | |
Columbia University Medical Center | Recruiting |
New York, New York, United States, 10032 | |
Contact: Colin Stein 212-304-7943 cs4125@cumc.columbia.edu | |
Principal Investigator: Edward Huey, MD |
Principal Investigator: | Edward Huey, MD | Columbia University |
Responsible Party: | Columbia University |
ClinicalTrials.gov Identifier: | NCT02862210 |
Other Study ID Numbers: |
NYSPI 7310 |
First Posted: | August 10, 2016 Key Record Dates |
Last Update Posted: | October 8, 2021 |
Last Verified: | October 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
Lithium Lithium Carbonate |
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 Neurodegenerative Diseases Frontotemporal Lobar Degeneration TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases |
Aphasia Speech Disorders Language Disorders Communication Disorders Neurobehavioral Manifestations Neurologic Manifestations Lithium Carbonate Antidepressive Agents Psychotropic Drugs Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antimanic Agents Tranquilizing Agents Central Nervous System Depressants Physiological Effects of Drugs |