Acute D2 Receptor Blockade Induced Neur… | Clinical Trial

Key information

Conditions

Imaging of the Brain and Antipsychotics Neuronal Network Changes

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Zucker-Hillside Hospital

Glen Oaks, New York, 11004, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Risperidone

Drug

We gave oral liquid of risperidone one time 1-2 mg depending on subject's weight.

Placebo

Other

We gave oral liquid without active risperidone (pt and provider were both double blinded)

Primary outcomes

Repeatable Battery for the Assessment of Neuropsychological Status

Time frame: 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 outcomes

Simpson-Angus Extrapyramidal Side Effects Scale

Time frame: 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 outcomes

Feedback-based Probabilistic Classification Task

Time frame: 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.

Sponsors and collaborators

Lead sponsor

Northwell Health