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Characterizing Clinical and Pharmacological Neuroimaging Biomarkers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03842800
Recruitment Status : Completed
First Posted : February 15, 2019
Last Update Posted : July 1, 2020
Sponsor:
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE February 14, 2019
First Posted Date  ICMJE February 15, 2019
Last Update Posted Date July 1, 2020
Actual Study Start Date  ICMJE April 1, 2013
Actual Primary Completion Date August 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 14, 2019)
Working Memory (WM) [ Time Frame: Up to 2 hours ]
The tool used to measure working memory (WM) is a spatial working memory task. We measure angular accuracy of spatial working memory, and better accuracy is indicated by a lower angular distance. Subjects are asked to centrally fixate, and a circle appears on the screen briefly, and then disappears. Afterwards they see a gray circle that is linked to a joystick and are asked to move the gray circle to where they best remembered the initial circle to be. We care about the angular distance between where the initial circle appeared and where they placed the gray circle. The low range is 0 degrees, and the high range is 180 degrees. Scores are presented as averages and standard deviations.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2020)
  • Behavior [ Time Frame: Up to 2 hours ]
    The tool used to measure behavior is a spatial working memory task. We measure angular accuracy of spatial working memory, and better accuracy is indicated by a lower angular distance. We expect that patients with schizophrenia would have higher angular distances (ie, worse accuracy) than healthy control subjects on placebo, and patients with ASD. We expect that HCS on ketamine would have higher angular distances (ie worse accuracy), compared to when they are not on ketamine, and that this would approach the performance of patients with SCZ. The low range is 0 degrees, and the high range is 180 degrees. Scores are presented as averages and standard deviations.
  • BOLD [ Time Frame: Up to 2 hours ]
    Regional BOLD (blood oxygen dependent) signal in the dorsolateral prefrontal cortex and parietal cortex. BOLD signal refers to the blood oxygen level dependent signal change measured using functional magnetic resonance imaging. It is an indirect marker of neural activity. The time series of BOLD signal changes is entered into a general linear model with our events of interest (WM maintenance) and we do statistics on the resulting beta weights.
  • Whole brain connectivity [ Time Frame: Up to 2 hours ]
    Whole-brain connectivity refers to the correlation in time series between voxels. These analysis will specifically focus on the delay period subjects are maintaining a spatial location.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2019)
  • Behavior [ Time Frame: Up to 2 hours ]
    The tool used to measure behavior is a spatial working memory task. We measure angular accuracy of spatial working memory, and better accuracy is indicated by a lower angular distance. We expect that patients with schizophrenia would have higher angular distances (ie, worse accuracy) than healthy control subjects on placebo, and patients with ASD. We expect that HCS on ketamine would have higher angular distances (ie worse accuracy), compared to when they are not on ketamine, and that this would approach the performance of patients with SCZ. The low range is 0 degrees, and the high range is 180 degrees. Scores are presented as averages and standard deviations.
  • BOLD [ Time Frame: Up to 2 hours ]
    Regional BOLD (blood oxygen dependent) signal in the dorsolateral prefrontal cortex and parietal cortex. BOLD signal refers to the blood oxygen level dependent signal change measured using functional magnetic resonance imaging. It is an indirect marker of neural activity. The time series of BOLD signal changes is entered into a general linear model with our events of interest (WM maintenance) and we do statistics on the resulting beta weights.
  • Whole brain connectivity [ Time Frame: Up to 2 hours ]
    Whole brain connectivity with the dorsolateral prefrontal cortex and parietal cortex as seeds. These analysis will specifically focus on the delay period subjects are maintaining a spatial location. Whole-brain connectivity refers to the correlation in time series between voxels.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Characterizing Clinical and Pharmacological Neuroimaging Biomarkers
Official Title  ICMJE Characterizing Clinical and Pharmacological Neuroimaging Biomarkers
Brief Summary This study is part of a larger overall study that seeks to characterize clinical and pharmacological neuroimaging biomarkers. The purpose of this registered protocol is understand the effect of emotion on cognitions by specifically examining the effect of reward processing on working memory in patients with schizophrenia.
Detailed Description

Cognition rarely occurs in the 'real world' in isolation, and typically occurs under emotional influences that may alter how cognition occurs. Understanding these motivational and cognitive interactions will help better assess mechanisms that underlie the cognitive and negative symptoms of schizophrenia.

To better understand the effect of emotion on cognitions, this study will examine the effect of reward processing on working memory in patients with schizophrenia. To this end, this will be a two-pronged approach.

The first prong, is to understand the neural mechanisms of incentivized spatial working memory processes. fMRI will be used and a paradigm will be employed that combines reward processing and working memory to understand how patients with schizophrenia recruit neural systems in response to rewarded working memory.

To further understand this, this study will compare the neural effects in patients with schizophrenia with patients with depression, another group of psychiatric patients who also suffer from cognitive and motivational deficits. Both of these groups suffer from cognitive and motivational deficits, yet the treatments and disease presentations differ.

It is hypothesized that the ways in which cognitive and motivational processes interact in the brain will have some similarities, but also differences, that distinguish the two psychiatric illnesses. As part of this aim, a group of typical, healthy adults subjects will be recruited as a control. A subset of healthy participants that passed the medical and psychiatric screen will be invited to participate in the ketamine portion of the study which will be completed during the MRI session.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Cognitive Impairment
Intervention  ICMJE
  • Other: MRI
    Patients and volunteers will receive an MRI.
    Other Name: Magnetic Resonance Imaging
  • Drug: Ketamine
    Ketamine will be administered to a subset of healthy controls that agree to receive the drug as part of receiving an MRI.
Study Arms  ICMJE
  • ASD Patients
    This arm consists of patients diagnosed with Autism Spectrum Disorder (ASD) that will receive an MRI.
    Intervention: Other: MRI
  • Schizophrenic Patients
    This arm consists of patients diagnosed with Schizophrenia that will receive an MRI.
    Intervention: Other: MRI
  • Healthy Controls
    This arm consists of healthy control volunteer participants that will receive an MRI.
    Intervention: Other: MRI
  • Experimental: Healthy Controls with Ketamine
    This arm consists of healthy control volunteer participants that elect to receive ketamine prior to receiving an MRI.
    Interventions:
    • Other: MRI
    • Drug: Ketamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 29, 2020)
143
Original Estimated Enrollment  ICMJE
 (submitted: February 14, 2019)
120
Actual Study Completion Date  ICMJE August 31, 2018
Actual Primary Completion Date August 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • For BOTH Non-Healthy Controls and Healthy Controls:
  • Right-handed as determined by the Edinburgh handedness questionnaire (Oldfield, 1971).
  • Premorbid IQ>70 determined by WAIS similarities and matrix reasoning subtests; Any history indicating learning disability, mental retardation, or attention deficit disorder will exclude the subject from participation.
  • Must speak or read English at least 8th grade level or higher and to complete study evaluations.
  • Must have intact vision or vision that can be corrected by glasses or contact lenses (corrected 20 20/20).
  • Must be able to tolerate enclosed spaces ** only if participating in MRI portion.
  • Female subjects must be postmenopausal for a least 1 year, surgically sterile, or using a reliable method of contraception at screening. Reliable methods of contraception include double-barrier methods (e.g. condom and diaphragm, condom and foam, condom and sponge), intrauterine devices, or hormonal birth control methods. Women with positive serum pregnancy results at screening or self-reporting of pregnancy will be excluded from the study. ** only if participating in MRI portion.
  • Must be free of metallic foreign objects in body, such as aneurysm clips or pacemakers, or a questionable history of metallic fragments ** only if participating in MRI portion.
  • For Non-Healthy Controls Participants:
  • Adult patients from the community meeting diagnostic criteria for schizophrenia, schizoaffective disorder, psychosis at risk syndrome, Major Depressive Disorder or autism spectrum disorders.
  • Young adults (16-21) who are at risk of developing schizophrenia (have "prodromal schizophrenia") may be involved in the study.

Exclusion Criteria:

  • For Healthy Controls:
  • Evidence or history of serious medical or physical conditions, including severe endocrine disorder (Cushing's, Lupus), heart disorder (past history of heart attacks, angina), or other major systemic medical conditions (kidney, MS, CP, blindness, serious physical disability).
  • Neurological conditions that might confound the results, including past stroke, seizures, dementia, brain tumor, brain surgery, neurological disease, head injury, or severe concussion (lasting >2 minutes in their life).
  • Individual not larger than 55" around shoulders and widest part of chest (approx. 250lb limit) ** only if participating in MRI portion.
  • Any other condition that is contra-indicated for fMRI if selected to participate in fMRI portion as determined by the MRRC safety screen. ** only if participating in MRI portion.
  • Meeting current diagnostic criteria for any DSM-IV Axis I psychiatric disorders, determined by SCID-NP / MINI interviews.
  • First-degree relative with Axis I DSM-IV disorder.
  • Regular use of psychoactive drugs including anxiolytics and antidepressants.
  • Meeting current DSM-IV abuse and/or dependence diagnostic criteria for other substances, other than nicotine in the past 6 months as determined by SCID-NP / MINI interviews (excluding caffeine).
  • For Non-Healthy Controls:
  • Medical. Evidence or history of serious medical or physical conditions, including severe endocrine disorder (Cushing's, Lupus), heart disorder (past history of heart attacks, angina), or other major systemic medical conditions (kidney, MS, CP, blindness, serious physical disability).
  • Neurological conditions that might confound the results, including past stroke, seizures, dementia, brain tumor, brain surgery, neurological disease, head injury, or severe concussion (lasting >2 minutes in your lifetime).
  • Individual not larger than 55" around shoulders and widest part of chest (approx. 250lb limit) ** only if participating in MRI portion.
  • Any other condition that is contra-indicated for fMRI if selected to participate in fMRI portion as determined by the MRRC safety screen. ** only if participating in MRI portion.
  • Meeting current diagnostic criteria for primary DSM-IV anxiety, depression or ADHD, determined by SCID-NP / MINI interview due to possible effects on cognition.
  • Medication change within the past 2 weeks to avoid transient effects of medication regiment change; medication type and dose will be carefully recorded and used as a covariate in all analyses. Of note, if patients are not on medication (but are clinically stable) they will be invited to participate.
  • History of any substance dependence disorder meeting DSM-IV criteria with the exception of nicotine and caffeine in the past 6 months. Meeting DSM-IV abuse and/or dependence diagnostic criteria for other substances in the past 6 months as determined by SCID / MINI interviews (again excluding caffeine and nicotine). Study will exclude for Specific Patterns of Substance Use. In addition, the study will exclude for use of stimulants, alcohol or heavy continued substance use defined as at least 3+ days per week for the duration of the last 6 months. In particular, we will not exclude for sporadic use of cannabis (defined as 3 or fewer marijuana cigarettes per week). Also, the study will exclude if a participant reports heavy habitual marijuana use, which we define more than 3 marijuana cigarettes per week over at least 90% of the weeks during a period of 6 months or more. Patterns of drug class, use pattern, frequency and history as well as the urine toxicology on the day of the assessment as well as all longitudinal followups will be assessed.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 60 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03842800
Other Study ID Numbers  ICMJE 1111009332
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alan Anticevic, PhD Yale University School of Medicine Department of Psychiatry
PRS Account Yale University
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP