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

Parallel Effects of Ketamine and Schizophrenia on Neurocognitive Function

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

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: ketamine

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VHA CT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: healthy control; Healthy controls will receive electrophysiological assessments before and after NMDA antagonist administration.	Drug: ketamine; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
P300, an ERP measure	Baseline and repeat assessment following ketamine

Secondary Outcome Measures

Outcome Measure	Time Frame
(Mismatch Negativity) MMN	Baseline and repeat assessment

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Handan Gunduz-Bruce, M.D., Yale Medical School

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: May 17, 2012
• First Submitted That Met QC Criteria: February 4, 2016
• First Posted (Estimate): February 5, 2016

Study Record Updates

• Last Update Posted (Estimate): February 5, 2016
• Last Update Submitted That Met QC Criteria: February 4, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: schizophrenia; glutamate; NMDA
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 0612002073