Acute D2 Receptor Blockade Induced Neuronal Network Changes in Human Volunteers

Study Overview
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Brief Summary
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To detect the effect of second-generation antipsychotic drug on the neural activity.

Detailed Description
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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.

Official Title
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Acute D2 Receptor Blockade Induced Neuronal Network Changes in Human Volunteers

Conditions
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Imaging of the Brain and Antipsychotics, Neuronal Network Changes

Intervention / Treatment
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* Drug: Risperidone
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Risperidone then Placebo<br>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. | Drug: Risperidone<br>* We gave oral liquid of risperidone one time 1-2 mg depending on subject's weight.<br>Other: Placebo<br>* We gave oral liquid without active risperidone (pt and provider were both double blinded)<br>|
| Experimental: Placebo then Risperidone<br>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 | Drug: Risperidone<br>* We gave oral liquid of risperidone one time 1-2 mg depending on subject's weight.<br>Other: Placebo<br>* We gave oral liquid without active risperidone (pt and provider were both double blinded)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | The change of RBANS scores between placebo and treatment conditions on two consecutive days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 times on risperidone day and on placebo day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Imaging, Risperidone, Placebo, antipsychotic