A Phase 2 interventional study of Tolcapone and Placebo in Frontotemporal Lobar Degeneration, sponsored by Columbia University. Completed at 1 site in United States. Open to participants aged 40 Years to 85 Years. Per ClinicalTrials.gov, last updated 2024-08-28.
Sponsored by Columbia University · Phase 2, Interventional, and Treatment
This study will test the effects of a medication called tolcapone on cognitive, behavioral, and language problems seen in patients with frontotemporal dementia (FTD). Tolcapone increases the amount of dopamine, a brain chemical that may be lowered in FTD. The study will see if tolcapone can improve thinking, behavior, and language in people with FTD and will look at the effects of the drug on brain activity.
Patients with FTD who are between 40 and 85 years of age may be eligible for this study.
Participants will be seen as outpatients at the Columbia University Medical Center approximately one a week for 4 weeks. They take tolcapone or a placebo (a look-alike pill with no active ingredient) during study week 1. During study week 3, those who took placebo during week 1 now take tolcapone for 1 week and those who took tolcapone now take placebo. In addition, patients undergo the following tests and procedures:
FTD is a significant cause of disability and death with an estimated prevalence of 15 cases per 100,000 persons in the 45- to 64-year-old age range. Despite the magnitude of this problem, there is currently a relative lack of understanding of the causes of, and treatments for, FTD, possibly because criteria for its diagnosis have only recently been developed. As an outcome of the proposed investigations, the investigators expect to determine the effects of cortical dopamine augmentation in FTD, evaluate the effect of dopamine augmentation on processing efficiency with fMRI, and explore the effects of a genetic polymorphism on symptom presentation and disease course. The research proposed in this protocol is significant because it could provide a new class of treatments for FTD, identify the fMRI findings associated with symptom improvement, and determine the contribution of a genetic polymorphism to symptom presentation and disease course.
2,172 studies on the registry are indexed under Dementia; 541 are open to participants now.
This study's enrollment of 28 is below the median of 83 across 1,629 interventional studies indexed under Dementia.
Browse Dementia studies →Columbia University is the lead sponsor of 1,103 studies on the registry; 193 are open to participants now.
Of its 172 completed or terminated interventional studies of FDA-regulated products, 142 (83%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants take placebo during study week 1 and then tolcapone during week 3. On Day 1, 100 mg of tolcapone/placebo will be taken at three specific times: once in the morning, once in the afternoon, once at night. Then, from Days 2-6, 200 mg of tolcapone/placebo will be taken three times a day: once in the morning, once in the afternoon, once at night. On Day 7, 200 mg of tolcapone/placebo will be taken only in the morning and afternoon. On Day 8, 200 mg of tolcapone/placebo will be taken only in the morning. After the last dose on Day 8 is taken, the wash-out period begins and lasts through Day 14.
Drug: Tolcapone · Drug: Placebo
Participants take tolcapone during study week 1 and then placebo during week 3. On Day 1, 100 mg of tolcapone/placebo will be taken at three specific times: once in the morning, once in the afternoon, once at night. Then, from Days 2-6, 200 mg of tolcapone/placebo will be taken three times a day: once in the morning, once in the afternoon, once at night. On Day 7, 200 mg of tolcapone/placebo will be taken only in the morning and afternoon. On Day 8, 200 mg of tolcapone/placebo will be taken only in the morning. After the last dose on Day 8 is taken, the wash-out period begins and lasts through Day 14.
Drug: Tolcapone · Drug: Placebo
200 mg by mouth three times a day
Also known as: Tasmar
200 mg by mouth three times a day
Also known as: Sugar pill
Reaction Time on the N-back Cognitive Test (0-back Condition)
In the N-back task, subjects are given a response pad with response buttons numbered 1, 2, 3, and 4 at the points of a diamond-shaped box and shown a random series of numbers from 1 to 4 appearing for 500 ms every 1.8 seconds at locations corresponding to the positions of the numbers on the response pad. Instructions presented on the screen above the diamond instruct patients to recall the stimulus seen "N" numbers previously. In the 0-back condition, the subjects are instructed to press the button with the number on the screen. Three blocks of 40 images will be administered during the working memory task for a total of 120 images.
Time frame: First intervention: Day 8 and Second intervention: Day 21
Reaction Time on the N-back Cognitive Test (1-back Condition)
In the N-back task, subjects are given a response pad with response buttons numbered 1, 2, 3, and 4 at the points of a diamond-shaped box and shown a random series of numbers from 1 to 4 appearing for 500 ms every 1.8 seconds at locations corresponding to the positions of the numbers on the response pad. Instructions presented on the screen above the diamond instruct patients to recall the stimulus seen "N" numbers previously. In the 1-back condition, the subjects are instructed to report the number presented one number back from the number displayed on the screen. Three blocks of 40 images will be administered during the working memory task for a total of 120 images.
Time frame: First intervention: Day 8 and Second intervention: Day 21
Score on Neuropsychiatric Inventory Questionnaire (NPI-Q)
The NPI-Q is a retrospective caregiver/informant-based interview that assesses 12 neuropsychiatric symptom domains including delusions, hallucinations, agitation/aggression, depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, night-time behavioral disturbances and appetite/eating disturbances. Each symptom within a domain are rated by the caregiver in terms of severity (1=mild to 3=severe). Total scores are calculated by adding the composite scores to obtain a score ranging from 0 (no symptoms, better outcome) to 36.
Time frame: First intervention: Day 8 and Second intervention: Day 21
Score on the Repeated Battery for the Assessment of Neurological Status (RBANS) for Dementia
The RBANS is a brief, individually administered test that captures multiple cognitive domains, including attention, language, visuospatial/constructional abilities, immediate memory, and delayed memory. Index scores range from 0 to 20 (better outcome) for each of the 5 domains tested and the composite scores are added to generated a total index score, which ranges from 0 to 100 (better outcome).
Time frame: First intervention: Day 8 and Second intervention: Day 21
Score on the Clinical Global Impressions (CGI) Scale
The CGI is often used in treatment studies as a proxy for global functioning and is a subjective score assigned by the treating physician that incorporates elements of illness severity, patient distress, patient impairment, and functioning. The CGI is given a numerical ranking each visit after the first, with 6=major worsening, 5=mild worsening, 4=no change, 3=mild improvement, and 2=major improvement. Scores range from a 2 (better outcome) to a 6 (worse outcome).
Time frame: First intervention: Day 8 and Second intervention: Day 21
| Milestone | Placebo Then Tolcapone | Tolcapone Then Placebo |
|---|---|---|
| Started | 14 | 14 |
| Completed | 14 | 14 |
| Not completed | 0 | 0 |
| Milestone | Placebo Then Tolcapone | Tolcapone Then Placebo |
|---|---|---|
| Started | 14 | 14 |
| Completed | 14 | 14 |
| Not completed | 0 | 0 |
| Milestone | Placebo Then Tolcapone | Tolcapone Then Placebo |
|---|---|---|
| Started | 14 | 14 |
| Completed | 14 | 14 |
| Not completed | 0 | 0 |
In the N-back task, subjects are given a response pad with response buttons numbered 1, 2, 3, and 4 at the points of a diamond-shaped box and shown a random series of numbers from 1 to 4 appearing for 500 ms every 1.8 seconds at locations corresponding to the positions of the numbers on the response pad. Instructions presented on the screen above the diamond instruct patients to recall the stimulus seen "N" numbers previously. In the 0-back condition, the subjects are instructed to press the button with the number on the screen. Three blocks of 40 images will be administered during the working memory task for a total of 120 images.
| milliseconds | Placebo | Tolcapone |
|---|---|---|
| Reaction Time on the N-back Cognitive Test (0-back Condition) | 7935 ± 2563 | 8322 ± 1940 |
In the N-back task, subjects are given a response pad with response buttons numbered 1, 2, 3, and 4 at the points of a diamond-shaped box and shown a random series of numbers from 1 to 4 appearing for 500 ms every 1.8 seconds at locations corresponding to the positions of the numbers on the response pad. Instructions presented on the screen above the diamond instruct patients to recall the stimulus seen "N" numbers previously. In the 1-back condition, the subjects are instructed to report the number presented one number back from the number displayed on the screen. Three blocks of 40 images will be administered during the working memory task for a total of 120 images.
| milliseconds | Placebo | Tolcapone |
|---|---|---|
| Reaction Time on the N-back Cognitive Test (1-back Condition) | 7060 ± 2475 | 8226 ± 2842 |
The NPI-Q is a retrospective caregiver/informant-based interview that assesses 12 neuropsychiatric symptom domains including delusions, hallucinations, agitation/aggression, depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, night-time behavioral disturbances and appetite/eating disturbances. Each symptom within a domain are rated by the caregiver in terms of severity (1=mild to 3=severe). Total scores are calculated by adding the composite scores to obtain a score ranging from 0 (no symptoms, better outcome) to 36.
| score on a scale | Placebo | Tolcapone |
|---|---|---|
| Score on Neuropsychiatric Inventory Questionnaire (NPI-Q) | 8.68 ± 4.83 | 8.21 ± 4.50 |
The RBANS is a brief, individually administered test that captures multiple cognitive domains, including attention, language, visuospatial/constructional abilities, immediate memory, and delayed memory. Index scores range from 0 to 20 (better outcome) for each of the 5 domains tested and the composite scores are added to generated a total index score, which ranges from 0 to 100 (better outcome).
| score on a scale | Placebo | Tolcapone |
|---|---|---|
| Score on the Repeated Battery for the Assessment of Neurological Status (RBANS) for Dementia | 67.89 ± 17.66 | 66.57 ± 18.32 |
The CGI is often used in treatment studies as a proxy for global functioning and is a subjective score assigned by the treating physician that incorporates elements of illness severity, patient distress, patient impairment, and functioning. The CGI is given a numerical ranking each visit after the first, with 6=major worsening, 5=mild worsening, 4=no change, 3=mild improvement, and 2=major improvement. Scores range from a 2 (better outcome) to a 6 (worse outcome).
| score on a scale | Placebo | Tolcapone |
|---|---|---|
| Score on the Clinical Global Impressions (CGI) Scale | 4.14 ± 0.76 | 3.75 ± 0.65 |
Collected over Up to 3 years to track any events during study participation.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| All Participants | 0/28 (0%) | 0/28 (0%) | 6/28 (21.4%) |
| Event | All Participants |
|---|---|
| Elevated liver enzymesHepatobiliary disorders | 6/28 |
| NauseaGeneral disorders | 4/28 |
| DiarrheaGastrointestinal disorders | 4/28 |
| HeadacheGeneral disorders | 4/28 |
| ConstipationGastrointestinal disorders | 3/28 |
| Upset StomachGastrointestinal disorders | 2/28 |
| Hyperactive Bowel SyndromeGastrointestinal disorders | 2/28 |
| Moderate fallInjury, poisoning and procedural complications | 2/28 |
| Age, Categorical(Participants) | All Participants |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 28 |
| >=65 years | 0 |
| Sex: Female, Male(Participants) | All Participants |
|---|---|
| Female | 14 |
| Male | 14 |
| Race (NIH/OMB)(Participants) | All Participants |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 2 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 1 |
| White | 25 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Reaction Time on the N-back Cognitive Test(milliseconds) | All Participants |
|---|---|
| 0-back accuracy | 9141 ± 2225 |
| 1-back accuracy | 7863 ± 2323 |
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