Acute D2 Receptor Blockade Induced Neuronal Network Changes in Human Volunteers

To detect the effect of second-generation antipsychotic drug on the neural activity.

Study Overview

• Status: Completed
• Conditions: Imaging of the Brain and Antipsychotics; Neuronal Network Changes
• Intervention / Treatment: Drug: Risperidone; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Glen Oaks, New York, United States, 11004
      • Zucker-Hillside Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Before every MRI except the 2nd and 4th which will occur during the MRI (5 times - 3 consecutive days)

Collaborators and Investigators

• Sponsor: Northwell Health
• Investigators: Principal Investigator: Miklos Argyelan, MD, Northwell Health

Publications and helpful links

General Publications

• Ho BC, Andreasen NC, Ziebell S, Pierson R, Magnotta V. Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Arch Gen Psychiatry. 2011 Feb;68(2):128-37. doi: 10.1001/archgenpsychiatry.2010.199.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: August 12, 2013
• First Submitted That Met QC Criteria: August 26, 2013
• First Posted (Estimate): August 29, 2013

Study Record Updates

• Last Update Posted (Actual): April 30, 2018
• Last Update Submitted That Met QC Criteria: March 30, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Imaging; Risperidone; Placebo; antipsychotic
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: 13-036