Trial Outcomes & Findings for Acute D2 Receptor Blockade Induced Neuronal Network Changes in Human Volunteers (NCT NCT01931059)

NCT ID: NCT01931059

Last Updated: 2018-04-30

Results Overview

This will measure the subject's cognitive performance. RBANS is a well-characterized repeatable battery to measure a wide array of cognitive performance in different cognitive domains. We will use Total Score in RBANS: five index scores are computed from the RBANS (immediate memory, language, visuospatial, attention, delayed memory) that are combined to provide the Total Score. The Total Score is expressed as a standardized score normalized to a population mean of 100, with a standard deviation of 15 (possible scores 40-135). Higher scores reflect better performance. More detailed information is available: Randolph C, Tierney MC, Mohr E, Chase TN (June 1998). "The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity". J Clin Exp Neuropsychol. 20 (3): 310-9. doi:10.1076/jcen.20.3.310.823. PMID 9845158. Here we calculated the difference of T-scaled total RBANS score between risperidone day and placebo day in all participants

Recruitment status

COMPLETED

Study phase

Target enrollment

11 participants

Primary outcome timeframe

The change of RBANS scores between placebo and treatment conditions on two consecutive days

Results posted on

2018-04-30

Participant Flow

Recruitment was done between 9/4/2013 and 9/19/2014 at the Department of Research at the Zucker Hillside Hospital.

Subjects were immediately randomized to either Arm 1 or Arm 2.

Participant milestones

Participant milestones
Measure	Risperidone Then Placebo This group will receive 2 mg (\>200lbs), 1.5mg (150-200lbs.) or 1 mg (\< 150lbs. of risperidone oral solution on the first day and a placebo on the second day, on third day they did not receive anything.	Placebo Then Risperidone This group will receive a placebo on the first day and 2mg (\> 200lbs.), 1.5mg (150-200lbs), or 1 mg (\<150lbs.) of risperidone oral solution on the second day, on the third day they did not receive anything.
Day 1 STARTED	6	5
Day 1 COMPLETED	6	4
Day 1 NOT COMPLETED	0	1
Day2 STARTED	6	4
Day2 COMPLETED	6	4
Day2 NOT COMPLETED	0	0
Day3 STARTED	6	4
Day3 COMPLETED	5	4
Day3 NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Risperidone Then Placebo This group will receive 2 mg (\>200lbs), 1.5mg (150-200lbs.) or 1 mg (\< 150lbs. of risperidone oral solution on the first day and a placebo on the second day, on third day they did not receive anything.	Placebo Then Risperidone This group will receive a placebo on the first day and 2mg (\> 200lbs.), 1.5mg (150-200lbs), or 1 mg (\<150lbs.) of risperidone oral solution on the second day, on the third day they did not receive anything.
Day 1 Pregnancy	0	1
Day3 Lost to Follow-up	1	0

Baseline Characteristics

Because right after enrollment pt inn placebo then risperidone arm was found to be pregnant and was ruled out from the study, no baseline information exist.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Risperidone Then Placebo n=6 Participants This group will receive 2 mg (\>200lbs), 1.5mg (150-200lbs.) or 1 mg (\< 150lbs. of risperidone oral solution on the first day and a placebo on the second day. Risperidone	Placebo Then Risperidone n=4 Participants This group will receive a placebo on the first day and 2mg (\> 200lbs.), 1.5mg (150-200lbs), or 1 mg (\<150lbs.) of risperidone oral solution on the second day Risperidone	Total n=10 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants • Because right after enrollment pt inn placebo then risperidone arm was found to be pregnant and was ruled out from the study, no baseline information exist.	0 Participants n=4 Participants • Because right after enrollment pt inn placebo then risperidone arm was found to be pregnant and was ruled out from the study, no baseline information exist.	0 Participants n=27 Participants • Because right after enrollment pt inn placebo then risperidone arm was found to be pregnant and was ruled out from the study, no baseline information exist.
Age, Categorical Between 18 and 65 years	6 Participants n=93 Participants • Because right after enrollment pt inn placebo then risperidone arm was found to be pregnant and was ruled out from the study, no baseline information exist.	4 Participants n=4 Participants • Because right after enrollment pt inn placebo then risperidone arm was found to be pregnant and was ruled out from the study, no baseline information exist.	10 Participants n=27 Participants • Because right after enrollment pt inn placebo then risperidone arm was found to be pregnant and was ruled out from the study, no baseline information exist.
Age, Categorical >=65 years	0 Participants n=93 Participants • Because right after enrollment pt inn placebo then risperidone arm was found to be pregnant and was ruled out from the study, no baseline information exist.	0 Participants n=4 Participants • Because right after enrollment pt inn placebo then risperidone arm was found to be pregnant and was ruled out from the study, no baseline information exist.	0 Participants n=27 Participants • Because right after enrollment pt inn placebo then risperidone arm was found to be pregnant and was ruled out from the study, no baseline information exist.
Age, Continuous	31.7 years STANDARD_DEVIATION 7.4 • n=93 Participants	37.5 years STANDARD_DEVIATION 10.4 • n=4 Participants	34.0 years STANDARD_DEVIATION 8.7 • n=27 Participants
Sex: Female, Male Female	3 Participants n=93 Participants • One subject exited study after enrollment due to pregnancy.	2 Participants n=4 Participants • One subject exited study after enrollment due to pregnancy.	5 Participants n=27 Participants • One subject exited study after enrollment due to pregnancy.
Sex: Female, Male Male	3 Participants n=93 Participants • One subject exited study after enrollment due to pregnancy.	2 Participants n=4 Participants • One subject exited study after enrollment due to pregnancy.	5 Participants n=27 Participants • One subject exited study after enrollment due to pregnancy.
Region of Enrollment United States	6 participants n=93 Participants • One subject exited study after enrollment due to pregnancy test came back positive.	4 participants n=4 Participants • One subject exited study after enrollment due to pregnancy test came back positive.	10 participants n=27 Participants • One subject exited study after enrollment due to pregnancy test came back positive.

PRIMARY outcome

Timeframe: The change of RBANS scores between placebo and treatment conditions on two consecutive days

Outcome measures

Outcome measures
Measure	Risperidone Then Placebo n=6 Participants This group will receive 2 mg (\>200lbs), 1.5mg (150-200lbs.) or 1 mg (\< 150lbs. of risperidone oral solution on the first day and a placebo on the second day. Risperidone	Placebo Then Risperidone n=4 Participants This group will receive a placebo on the first day and 2mg (\> 200lbs.), 1.5mg (150-200lbs), or 1 mg (\<150lbs.) of risperidone oral solution on the second day Risperidone	ON - REWARD Subject's performance during the peak of the risperidone effect in the reward part of the task	OFF - REWARD Subject's performance after placebo administration in the reward part of the task
Repeatable Battery for the Assessment of Neuropsychological Status	-1.5 RBANS T-Scale point difference Standard Deviation 6.6	-0.5 RBANS T-Scale point difference Standard Deviation 7.5	—	—

SECONDARY outcome

Timeframe: 2 times on risperidone day and on placebo day

Population: We analyzed the difference between patients who received drug versus placebo on the first day. 0 would mean no side effects after administration of risperidone or placebo.

The secondary outcome measures are the scores from side effect scales (Simpson-Angus Extrapyramidal Side Effects. It will measured in synchrony with Repeated Battery for the Assessment of Neuropsychological Status to explore if any of these measures would correlate with network changes in the brain. The Simpson-Angus scale is 0 if there is no extrapyramidal side effects, and is higher the worst the symptoms are.

Outcome measures

Outcome measures
Measure	Risperidone Then Placebo n=6 Participants This group will receive 2 mg (\>200lbs), 1.5mg (150-200lbs.) or 1 mg (\< 150lbs. of risperidone oral solution on the first day and a placebo on the second day. Risperidone	Placebo Then Risperidone n=4 Participants This group will receive a placebo on the first day and 2mg (\> 200lbs.), 1.5mg (150-200lbs), or 1 mg (\<150lbs.) of risperidone oral solution on the second day Risperidone	ON - REWARD Subject's performance during the peak of the risperidone effect in the reward part of the task	OFF - REWARD Subject's performance after placebo administration in the reward part of the task
Simpson-Angus Extrapyramidal Side Effects Scale	0 units on a scale Standard Deviation 0	0 units on a scale Standard Deviation 0	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Before every MRI except the 2nd and 4th which will occur during the MRI (5 times - 3 consecutive days)

Population: We lumped individuals from both arms to four groups depending on the task and the medication status and calculated the percentage of correct responses. Due to computer problems 3 subjects' data were lost.

On each trial, participants will view one of four images and will be asked to guess whether it belongs to Category A or B. For each participant, the four images will be randomly assigned to be stimuli S1, S2, S3 and S4 (these are abstract visual stimuli denoted with numbers (stiumulus 1, stimulus 2, etc). A different set of similar images (S5-S8; S9-S12, etc) will be used for repeated testing. On any given trial, stimuli S1 and S3 will belong to Category A with 90% probability and to Category B with 10% probability, while stimuli S2 and S4 will belong to Category B with 90% probability and to Category A with 10% probability. Stimuli S1 and S2 will be used in the reward-learning task and S3 and S4 in punishment-learning task. Two stimuli per valence will be employed in order to balance category outcome frequencies, so that one stimulus in each task will be associated with each outcome.

Outcome measures

Outcome measures
Measure	Risperidone Then Placebo n=7 Participants This group will receive 2 mg (\>200lbs), 1.5mg (150-200lbs.) or 1 mg (\< 150lbs. of risperidone oral solution on the first day and a placebo on the second day. Risperidone	Placebo Then Risperidone n=7 Participants This group will receive a placebo on the first day and 2mg (\> 200lbs.), 1.5mg (150-200lbs), or 1 mg (\<150lbs.) of risperidone oral solution on the second day Risperidone	ON - REWARD n=7 Participants Subject's performance during the peak of the risperidone effect in the reward part of the task	OFF - REWARD n=7 Participants Subject's performance after placebo administration in the reward part of the task
Feedback-based Probabilistic Classification Task	52.86 percentage of correct response Standard Deviation 17.99	71.43 percentage of correct response Standard Deviation 21.93	61.43 percentage of correct response Standard Deviation 27.34	70.00 percentage of correct response Standard Deviation 25.17

Adverse Events

Risperidone Then Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo Then Risperidone

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Miklos Argyelan

Northwell Health

Phone: 718-470-8175

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place