Trial Outcomes & Findings for Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia (NCT NCT02862210)
NCT ID: NCT02862210
Last Updated: 2025-02-03
Results Overview
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.
COMPLETED
PHASE2
17 participants
12 weeks
2025-02-03
Participant Flow
A total of 17 participants signed a consent form. One participant was a screen failure, resulting in randomization of 16 participants.
Participant milestones
| Measure |
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.
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.
|
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.
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.
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
7
|
|
Overall Study
COMPLETED
|
9
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia
Baseline characteristics by cohort
| Measure |
Lithium Carbonate
n=9 Participants
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.
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.
|
Placebo
n=7 Participants
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.
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.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
40-55 years
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Age, Customized
56-65 years
|
5 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Age, Customized
66-75 years
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Age, Customized
76-85 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=99 Participants
|
7 participants
n=107 Participants
|
16 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 12 weeksThe 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.
Outcome measures
| Measure |
Lithium Carbonate
n=9 Participants
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.
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.
|
Placebo
n=7 Participants
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.
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)
|
7.14 score on a scale
Standard Error 1.1
|
5.75 score on a scale
Standard Error 1.28
|
SECONDARY outcome
Timeframe: 12 weeksResponder 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).
Outcome measures
| Measure |
Lithium Carbonate
n=9 Participants
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.
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.
|
Placebo
n=7 Participants
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.
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.
|
|---|---|---|
|
Number of Responders in the Lithium and Placebo Groups
|
0 participants
|
0 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 weeksNPI domain "Aberrant Motor Behaviors" will be observed to test the effect of lithium on repetitive behaviors as compared to placebo, by examining whether participants taking lithium show a greater reduction in their "Aberrant Motor Behaviors" NPI domain score. Scores range from from 0-12, with 0 being no symptoms and 12 being very frequent and severe symptoms.
Outcome measures
| Measure |
Lithium Carbonate
n=9 Participants
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.
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.
|
Placebo
n=7 Participants
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.
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 Motor Symptoms as Measured by the NPI
|
6.83 score on a scale
Standard Error 0.95
|
8.8 score on a scale
Standard Error 1.23
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 weeksThe 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. Total scores range from 0 to 96 with a higher score indicating a worse outcome.
Outcome measures
| Measure |
Lithium Carbonate
n=9 Participants
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.
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.
|
Placebo
n=7 Participants
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.
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.
|
|---|---|---|
|
Presence of Adverse Events as Measured by the Treatment Emergent Symptoms Scale (TESS)
|
31.1 score on a scale
Standard Error 0.55
|
31 score on a scale
Standard Error 0.66
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and 12 weeksThe 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. The mean change of NPI "Agitation/Aggression" score as a function of BDNF level change from baseline to 12 weeks will be reported. Scores range from from 0-12, with 0 being no symptoms and 12 being very frequent and severe symptoms.
Outcome measures
| Measure |
Lithium Carbonate
n=9 Participants
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.
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.
|
Placebo
n=7 Participants
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.
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.
|
|---|---|---|
|
The Relationship Between Changes in Brain-derived Neurotropic Factor (BDNF) Serum Levels and Changes in NPI "Agitation/Aggression" Score
|
0.71 score on a scale
Standard Error 1.91
|
-1.6 score on a scale
Standard Error 2.11
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and 12 weeksThe 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. Aberrant motor behavior is characterized by repetitive movements and inability to sit still. The mean change of NPI Aberrant Motor Behavior score as a function of BDNF level change from baseline to 12 weeks will be reported. Scores range from from 0-12, with 0 being no symptoms and 12 being very frequent and severe symptoms.
Outcome measures
| Measure |
Lithium Carbonate
n=9 Participants
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.
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.
|
Placebo
n=7 Participants
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.
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.
|
|---|---|---|
|
The Relationship Between Changes in Brain-derived Neurotropic Factor (BDNF) Serum Levels and Changes in NPI "Aberrant Motor Behavior" Score
|
0.4 score on a scale
Standard Error 11.33
|
0.4 score on a scale
Standard Error 1.83
|
Adverse Events
Lithium Carbonate
Placebo
Serious adverse events
| Measure |
Lithium Carbonate
n=9 participants at risk
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.
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.
|
Placebo
n=7 participants at risk
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.
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.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Fall
|
22.2%
2/9 • Number of events 2 • 12 weeks
|
0.00%
0/7 • 12 weeks
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place