Trial Outcomes & Findings for Effects of Tolcapone on Frontotemporal Dementia (NCT NCT00604591)

NCT ID: NCT00604591

Last Updated: 2024-08-28

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 28 participants
• Primary outcome timeframe: First intervention: Day 8 and Second intervention: Day 21
• Results posted on: 2024-08-28

Participant Flow

Participant milestones

Measure	Placebo Then Tolcapone Participants take placebo during study week 1 and then tolcapone during week 3. On Day 1, 100 mg of 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 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 placebo will be taken only in the morning and afternoon. On Day 8, 200 mg of 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.	Tolcapone Then Placebo Participants take tolcapone during study week 1 and then placebo during week 3. On Day 1, 100 mg of tolcapone 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 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 will be taken only in the morning and afternoon. On Day 8, 200 mg of tolcapone 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.
First Intervention (Day 1 to Day 8) STARTED	14	14
First Intervention (Day 1 to Day 8) COMPLETED	14	14
First Intervention (Day 1 to Day 8) NOT COMPLETED	0	0
Washout (Day 9 to Day 14) STARTED	14	14
Washout (Day 9 to Day 14) COMPLETED	14	14
Washout (Day 9 to Day 14) NOT COMPLETED	0	0
Second Intervention (Day 15 to Day 24) STARTED	14	14
Second Intervention (Day 15 to Day 24) COMPLETED	14	14
Second Intervention (Day 15 to Day 24) NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effects of Tolcapone on Frontotemporal Dementia

Baseline characteristics by cohort

Measure	All Participants n=28 Participants Includes all participants who participated in the study since all participants received both tolcapone and placebo in this cross-over designed study. Participants were randomly assigned to start on tolcapone or placebo and then crossed over to received the alternative treatment after a wash-out period.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	28 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Reaction Time on the N-back Cognitive Test 0-back accuracy	9141 milliseconds STANDARD_DEVIATION 2225 • n=5 Participants
Reaction Time on the N-back Cognitive Test 1-back accuracy	7863 milliseconds STANDARD_DEVIATION 2323 • n=5 Participants

PRIMARY outcome

Timeframe: First intervention: Day 8 and Second intervention: Day 21

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.

Outcome measures

Measure	Placebo n=28 Participants Participants take 100 mg of the placebo orally three times a day during the first day and then 200 mg orally for the next six days. On the seventh day, participants take 200 mg placebo twice a day. On the eighth day, particpants take 200 mg placebo once.	Tolcapone n=28 Participants Participants take 100 mg of the tolcapone orally three times a day during the first day and then 200 mg orally for the next six days. On the seventh day, participants take 200 mg tolcapone twice a day. On the eighth day, particpants take 200 mg tolcapone once.
Reaction Time on the N-back Cognitive Test (0-back Condition)	7935 milliseconds Standard Deviation 2563	8322 milliseconds Standard Deviation 1940

PRIMARY outcome

Timeframe: First intervention: Day 8 and Second intervention: Day 21

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.

Outcome measures

Measure	Placebo n=28 Participants Participants take 100 mg of the placebo orally three times a day during the first day and then 200 mg orally for the next six days. On the seventh day, participants take 200 mg placebo twice a day. On the eighth day, particpants take 200 mg placebo once.	Tolcapone n=28 Participants Participants take 100 mg of the tolcapone orally three times a day during the first day and then 200 mg orally for the next six days. On the seventh day, participants take 200 mg tolcapone twice a day. On the eighth day, particpants take 200 mg tolcapone once.
Reaction Time on the N-back Cognitive Test (1-back Condition)	7060 milliseconds Standard Deviation 2475	8226 milliseconds Standard Deviation 2842

SECONDARY outcome

Timeframe: First intervention: Day 8 and Second intervention: Day 21

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.

Outcome measures

Measure	Placebo n=28 Participants Participants take 100 mg of the placebo orally three times a day during the first day and then 200 mg orally for the next six days. On the seventh day, participants take 200 mg placebo twice a day. On the eighth day, particpants take 200 mg placebo once.	Tolcapone n=28 Participants Participants take 100 mg of the tolcapone orally three times a day during the first day and then 200 mg orally for the next six days. On the seventh day, participants take 200 mg tolcapone twice a day. On the eighth day, particpants take 200 mg tolcapone once.
Score on Neuropsychiatric Inventory Questionnaire (NPI-Q)	8.68 score on a scale Standard Deviation 4.83	8.21 score on a scale Standard Deviation 4.50

SECONDARY outcome

Timeframe: First intervention: Day 8 and Second intervention: Day 21

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).

Outcome measures

Measure	Placebo n=28 Participants Participants take 100 mg of the placebo orally three times a day during the first day and then 200 mg orally for the next six days. On the seventh day, participants take 200 mg placebo twice a day. On the eighth day, particpants take 200 mg placebo once.	Tolcapone n=28 Participants Participants take 100 mg of the tolcapone orally three times a day during the first day and then 200 mg orally for the next six days. On the seventh day, participants take 200 mg tolcapone twice a day. On the eighth day, particpants take 200 mg tolcapone once.
Score on the Repeated Battery for the Assessment of Neurological Status (RBANS) for Dementia	67.89 score on a scale Standard Deviation 17.66	66.57 score on a scale Standard Deviation 18.32

SECONDARY outcome

Timeframe: First intervention: Day 8 and Second intervention: Day 21

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).

Outcome measures

Measure	Placebo n=28 Participants Participants take 100 mg of the placebo orally three times a day during the first day and then 200 mg orally for the next six days. On the seventh day, participants take 200 mg placebo twice a day. On the eighth day, particpants take 200 mg placebo once.	Tolcapone n=28 Participants Participants take 100 mg of the tolcapone orally three times a day during the first day and then 200 mg orally for the next six days. On the seventh day, participants take 200 mg tolcapone twice a day. On the eighth day, particpants take 200 mg tolcapone once.
Score on the Clinical Global Impressions (CGI) Scale	4.14 score on a scale Standard Deviation 0.76	3.75 score on a scale Standard Deviation 0.65

Adverse Events

All Participants

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	All Participants n=28 participants at risk Adverse events data were not collected per Arm, therefore adverse events cannot be reported per Arm.
Hepatobiliary disorders Elevated liver enzymes	21.4% 6/28 • Number of events 6 • Up to 3 years to track any events during study participation.
General disorders Nausea	14.3% 4/28 • Number of events 4 • Up to 3 years to track any events during study participation.
Gastrointestinal disorders Diarrhea	14.3% 4/28 • Number of events 4 • Up to 3 years to track any events during study participation.
General disorders Headache	14.3% 4/28 • Number of events 4 • Up to 3 years to track any events during study participation.
Gastrointestinal disorders Constipation	10.7% 3/28 • Number of events 3 • Up to 3 years to track any events during study participation.
Gastrointestinal disorders Upset Stomach	7.1% 2/28 • Number of events 2 • Up to 3 years to track any events during study participation.
Gastrointestinal disorders Hyperactive Bowel Syndrome	7.1% 2/28 • Number of events 2 • Up to 3 years to track any events during study participation.
Injury, poisoning and procedural complications Moderate fall	7.1% 2/28 • Number of events 2 • Up to 3 years to track any events during study participation.

Additional Information

Edward D. Huey, MD

Columbia University

Phone: 212-305-1134

Email: edh2126@cumc.columbia.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place