Frontotemporal Dementia (FTD)Phase 2LithiumNCT02862210
Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia
A Phase 2 study testing Lithium Carbonate in people with Frontotemporal Dementia (FTD), run by Columbia University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Frontotemporal Dementia (FTD)
- What is being tested?
- Lithium Carbonate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jan 2017to 20 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10032
About this study
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.
Read the 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.
- Conditions
- Frontotemporal Dementia (FTD)
- Being tested
- Lithium Carbonate, Placebo
- Keywords
- Lithium, Lithium Carbonate
- Medical subject headings
- Frontotemporal Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lithium CarbonateDrug
Also called Lithobid
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (1)
Number of Responders in the Lithium and Placebo Groups
Responder defined as 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).
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2016 (estimated)
- Study start27 Jan 2017
- Primary completion20 Nov 2022
- Study completion20 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Frontotemporal Dementia (FTD)Studies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Alzheimer's Drug Discovery Foundation
- Responsible party
- Principal investigator, Edward D Huey, MD, Columbia University
- Investigators
- Edward Huey, MD, Principal investigator, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02862210
- Sponsor's protocol ID
- NYSPI 7310
- Acronym
- Lithium
- Status last verified
- Jan 2025
- First submitted
- 7 Aug 2016
- Last updated
- 3 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia
- ClinicalTrials.gov ID
- NCT02862210
- Acronym / sponsor ID
- Lithium / NYSPI 7310
- Conditions
- Frontotemporal Dementia (FTD)
- Keywords
- Lithium, Lithium Carbonate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Alzheimer's Drug Discovery Foundation
- Study start
- 27 Jan 2017 (actual)
- Primary completion
- 20 Nov 2022 (actual)
- Study completion
- 20 Nov 2022 (actual)
- First posted
- 10 Aug 2016 (estimated)
- Results
- Posted 3 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lithium carbonate | Experimental | Drug: Lithium CarbonateLithium 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 | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lithium CarbonateAlso: LithobidLithium 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 |
| PlaceboPlacebo 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. | Drug | Placebo |
Primary outcome
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). 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.
1 secondary outcome
Number of Responders in the Lithium and Placebo Groups
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward Huey, MD principal investigator
Brown University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lithium Carbonate in people with Frontotemporal Dementia (FTD), run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Agitation and Aggression as Measured by the Neuropsychiatric Inventory Scale (NPI) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.