Imaging of the Brain and Antipsychotics, Neuronal Network Changes
Conditions
Keywords
Imaging, Risperidone, Placebo, antipsychotic
Brief summary
To detect the effect of second-generation antipsychotic drug on the neural activity.
Detailed description
To detect functional correlation changes in the brain with anti-psychotic drug administration as compared to placebo, and b.) to measure if these changes correlate with the plasma level of anti-psychotic, and c.) to evaluate if these changes correlate with drug induced symptoms and changes in cognitive function.
Interventions
DRUGRisperidone
We gave oral liquid of risperidone one time 1-2 mg depending on subject's weight.
OTHERPlacebo
We gave oral liquid without active risperidone (pt and provider were both double blinded)
Sponsors
Northwell Health
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Between 18 and 60 years of age * Subject is competent to provide informed consent
Exclusion criteria
* Mini Mental Status Exam is less than 28 * Past or current history of any psychotic illness in the subject or in first degree family members * Self report of illicit drug use (except marijuana) in the past. Use of marijuana during the last 3 month... * Any use of antipsychotic in the past. * Any neuro-anatomical lesions on previous brain imaging * Any use of D2 receptor blocking agent (such as antiemetics) in the last two weeks. * Any use of any psychotropic medications (SSRI, mood stabilizers, benzodiazepines, stimulants) in the last month. * MRI contraindications * Any cardiovascular or cerebrovascular diseases or conditions that predispose patients to hypotension (eg. dehydration, hypovolemia, antihypertensive medication) * Subjects with diabetes mellitus, metabolic syndrome, hepatic or renal impairment, seizure disorder and any neurological disorder * QTc interval longer than 450 ms for male and 470 ms for female * Subjects who used any medications in the last two weeks (to avoid any possible drug-drug interactions) * Pregnancy * Individuals who are illiterate and/or visually impaired
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Repeatable Battery for the Assessment of Neuropsychological Status | The change of RBANS scores between placebo and treatment conditions on two consecutive days | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Simpson-Angus Extrapyramidal Side Effects Scale | 2 times on risperidone day and on placebo day | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Feedback-based Probabilistic Classification Task | Before every MRI except the 2nd and 4th which will occur during the MRI (5 times - 3 consecutive days) | 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment was done between 9/4/2013 and 9/19/2014 at the Department of Research at the Zucker Hillside Hospital.
Pre-assignment details
Subjects were immediately randomized to either Arm 1 or Arm 2.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Risperidone | 6 |
| 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
Risperidone | 4 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Day 1 | Pregnancy | 0 | 1 |
| Day3 | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo Then Risperidone | Risperidone Then Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 6 Participants | 10 Participants |
| Age, Continuous | 37.5 years STANDARD_DEVIATION 10.4 | 31.7 years STANDARD_DEVIATION 7.4 | 34.0 years STANDARD_DEVIATION 8.7 |
| Region of Enrollment United States | 4 participants | 6 participants | 10 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 4 |
Outcome results
Primary
Repeatable Battery for the Assessment of Neuropsychological Status
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
Time frame: The change of RBANS scores between placebo and treatment conditions on two consecutive days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Risperidone Then Placebo | Repeatable Battery for the Assessment of Neuropsychological Status | -1.5 RBANS T-Scale point difference | Standard Deviation 6.6 |
| Placebo Then Risperidone | Repeatable Battery for the Assessment of Neuropsychological Status | -0.5 RBANS T-Scale point difference | Standard Deviation 7.5 |
Secondary
Simpson-Angus Extrapyramidal Side Effects Scale
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Risperidone Then Placebo | Simpson-Angus Extrapyramidal Side Effects Scale | 0 units on a scale | Standard Deviation 0 |
| Placebo Then Risperidone | Simpson-Angus Extrapyramidal Side Effects Scale | 0 units on a scale | Standard Deviation 0 |
Other Pre-specified
Feedback-based Probabilistic Classification Task
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Risperidone Then Placebo | Feedback-based Probabilistic Classification Task | 52.86 percentage of correct response | Standard Deviation 17.99 |
| Placebo Then Risperidone | Feedback-based Probabilistic Classification Task | 71.43 percentage of correct response | Standard Deviation 21.93 |
| ON - REWARD | Feedback-based Probabilistic Classification Task | 61.43 percentage of correct response | Standard Deviation 27.34 |
| OFF - REWARD | Feedback-based Probabilistic Classification Task | 70.00 percentage of correct response | Standard Deviation 25.17 |