Parallel Effects of Schizophrenia and N-methyl-D-aspartate (NMDA) Antagonism

Brief Summary

This study investigates the common features of electrophysiological measures in schizophrenia and effects of NMDA antagonist ketamine in healthy volunteers.

Intervention / Treatment

  • Ketamine (DRUG)
    For healthy volunteer arm of study, NMDA antagonist ketamine will be administered. 0.23 mg/kg over 1 minute, followed by 0.58 mg/kg/hour for 30 minutes, followed by 0.29 mg/kg/hour for 50 minutes. No drug administration for patients with schizophrenia

Condition or Disease

  • Schizophrenia

Phase

  • Phase 1
  • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 21 Years to 45 Years
    Enrollment: 33 (ACTUAL)
    Funded by: Other|Industry
    Allocation: N/A

    Masking

    Clinical Trial Dates

    Start date: Dec 01, 2007
    Primary Completion: Dec 01, 2011 ACTUAL
    Completion Date: Dec 01, 2011 ACTUAL
    Study First Posted: Feb 05, 2016 ESTIMATED
    Results First Posted: Aug 31, 2020
    Last Updated: Feb 04, 2016

    Sponsors / Collaborators

    Lead Sponsor: Yale University
    Lead sponsor is responsible party
    Responsible Party: N/A

    Participant Groups

    • Healthy controls will receive electrophysiological assessments before and after NMDA antagonist administration.

    Eligibility Criteria

    Sex: All
    Minimum Age: 21
    Maximum Age: 45
    Age Groups: Adult
    Healthy Volunteers: Yes

    Subjects for the Ketamine experiment(Healthy control experiment):

    Inclusion Criteria:

    1. Male or female
    2. 21-45 years old
    3. Deemed healthy by the Structured Clinical Interview for DSM-NP (SCID-NP) and collateral information. Subjects will need to provide the name of a person, preferably a family member, whom the research team can contact to corroborate information.

    Exclusion Criteria:

    1. Lifetime diagnosis of DSM-IV substance dependence (except caffeine and nicotine).
    2. Substance abuse, as per clinical judgment, in the past 1 year.
    3. Current or past DSM-IV Axis-I diagnosis.
    4. A history of significant medical/neurological disease such as cardiac, thyroid, renal, hepatic or neurological. Unstable medical condition based on EKG, vital signs, physical examination and laboratory work-up.
    5. A hearing deficit greater than 30 dB in both ears detected using a Welch-Allyn audioscope (500, 1000, 2000 and 4000 Hz threshold will be evaluated) at screening.
    6. Major current or recent (\<6 weeks) stressors.
    7. History of counseling, except if counseling was for a life circumstance disorder (e.g., bereavement, divorce) or in the opinion of the investigator, is not clinically significant.
    8. Lifetime history of treatment with any psychotropic medications for \> 1 month duration suggestive of psychiatric illness.
    9. Current or past Axis I diagnosis of schizophrenia or bipolar disorder in first-degree relatives.
    10. Any medication that could interfere with either the safety of the study and/or the outcome measures.
    11. Use of any illicit substances in the 4 weeks prior to beginning study participation.
    12. Any history indicating learning disability, mental retardation, or attention deficit disorder.
    13. History of head injury with loss of consciousness greater than fifteen minutes.
    14. Any other condition or medication, which in the opinion of the investigator would preclude participation in the study.
    15. Non-English speaking.
    16. Known sensitivity to ketamine.

    Subjects for the Schizophrenia experiment:

    Inclusion Criteria for control subjects:

    1. Male or female
    2. 21-45 years old
    3. No past or present Axis I diagnosis, as determined by the SCID-NP

    Exclusion Criteria for control subjects:

    1. Lifetime diagnosis of DSM-IV substance dependence (except caffeine and nicotine).
    2. Substance abuse, as per clinical judgment, in the past 1 year
    3. A history of significant medical/neurological disease such as cardiac, thyroid, renal, hepatic or neurological.
    4. A hearing deficit greater than 30dB in both ears detected using a Welch-Allyn audioscope (500, 1000, 2000 and 4000 Hz threshold will be evaluated) at screening.
    5. Axis I diagnosis of schizophrenia or bipolar disorder in first-degree relatives.
    6. History of head injury with loss of consciousness greater than fifteen minutes
    7. Any other condition or medication, which in the opinion of the investigator would preclude participation in the study.
    8. Non-English speaking.

    Inclusion Criteria for patients:

    1. Male or female
    2. 21-45 years old
    3. Diagnosed with DSM-IV schizophrenia based on a SCID-IP interview for patients.
    4. Stable dose of antipsychotic medications for at least 2 weeks prior to beginning study participation.
    5. Score either in the 1-3 (high functioning) range or in the 5-7 (low functioning) range of the Global Functioning Scale from the MSIF based on a screening interview.

    Exclusion Criteria:

    1. Lifetime diagnosis of DSM-IV substance dependence (except caffeine and nicotine).
    2. Substance abuse, as per clinical judgment, in the past 1 year
    3. A history of significant medical/neurological disease such as cardiac, thyroid, renal, hepatic or neurological.
    4. A hearing deficit greater than 30dB in both ears detected using a Welch-Allyn audioscope (500, 1000, 2000 and 4000 Hz threshold will be evaluated) at screening.
    5. History of head injury with loss of consciousness greater than fifteen minutes.
    6. Any other condition or medication, which in the opinion of the investigator would preclude participation in the study.
    7. Non-English speaking.

    -

    Primary Outcomes
    • P300, an ERP measure Baseline and repeat assessment following ketamine
    Secondary Outcomes
    • (Mismatch Negativity) MMN Baseline and repeat assessment

    More Details

    NCT Number: NCT02675530
    Other IDs: 0612002073
    Study URL: https://clinicaltrials.gov/study/NCT02675530
    Last updated: Sep 29, 2023