Glutamatergic Mechanisms of Psychosis and Target Engagement (SA1)

NCT04589208 | Suspended Phase 1 DMC FDA Drug

• 2 other identifiers: 8063R01MH123142-01A1
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

50 healthy volunteers (HV) will participate in 2 identical ketamine-induced pharmacoBOLD (phBOLD) sessions at least 7 days apart. On both days, clinical assessments will be performed following removal of the subject from the scanner. HV will be discharged home after clearance by the study physician. This study will assign ketamine doses in successive 10 subject cohorts. The ketamine dose for the 1st cohort will start at 0.08 mg/kg. For subsequent cohorts, the bolus will be successively reduced or increased by 0.02 mg/kg (n=10/dose) to determine the lowest dose of ketamine that still produces a robust phBOLD response. The study will be subject and rater blind, i.e. subjects and raters, will be blinded to the treatment (ketamine dose) group. The study physician will be aware of the ketamine dose, and ketamine dose will be the same for both sessions. Subjects will not be told what the exact ketamine dose they will receive, but it will be based on their weight and will be no higher than 0.08 mg/kg.

Conditions

Healthy

Keywords

schizophrenia

Outcome Measures

Primary Outcomes (2)

• PhBOLD

  Pharmacological Blood-oxygen-level Dependent (phBOLD) Response to ketamine

  Compare within day changes in phBOLD in response to infusion of ketamine, as measured by resting state fMRI. Calculated by post-pre changes, with higher values indicating higher response. Two scans will be completed, 7 days apart

• Brief Psychiatric Rating Scale (BPRS)

  Clinical rating scale assessing common psychiatric symptoms

  Compare within day changes in BPRS in response to infusion of ketamine, as measured by the clinical scale. Calculated by post-pre changes, with higher values indicating higher response. Two scans will be completed, 7 days apart

Study Arms (1)

Ketamine

EXPERIMENTAL

ketamine

Drug: Ketamine Hydrochloride

Interventions

Ketamine Hydrochloride DRUG

We will assign ketamine doses in successive 10 subject cohorts. The ketamine dose for the 1st cohort will start at 0.08 mg/kg. For subsequent cohorts, the bolus will be successively reduced or increased by 0.02 mg/kg (n=10/dose) to determine the lowest dose of ketamine that still produces a robust phBOLD response

Ketamine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18-55
• Medically healthy, as assessed by study physician
• Capable of understanding the study procedures and able to provide informed consent
• Eligible men and women must agree to use a reliable method of birth control (for example, use of oral contraceptives or Norplant; a reliable barrier method of birth control diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) during the study. Women who are post-menopausal or otherwise not of childbearing potential are also eligible.

You may not qualify if:

• Current or past Axis I psychiatric history (including Substance Use Disorder/Alcohol Use Disorder, with the exception of nicotine use disorder)
• Positive urine toxicology
• History of recreational ketamine use, recreational PCP use, or an adverse reaction to ketamine. Subjects who have participated in prior research ketamine studies will be eligible. Subjects can have infusions not more frequently than biweekly, and not more than 1/month on average, therefore subjects entering the study will need to wait one month if they had a single infusion and 6 weeks if they have had two closely spaced infusions.
• History of first-degree relative with schizophrenia
• History of violence, including any history of using a gun, knife, or other weapon with intent to harm someone, as well as a more than one physical fight without a weapon after the age of 18 years old (not including fights that happen during sports competition).
• Presence or positive history of significant medical illness, including renal problems (GFR\<60), high blood pressure (defined as systolic blood pressure (SBP) \> 140 or diastolic blood pressure (DBP) \> 90), low blood pressure (SBP \< 100, DBP \< 60), orthostatic blood pressure at baseline (change in mean arterial pressure \[1/3 systolic + 2/3 diastolic\] of \> 20%), cardiac illness, or clinically significant abnormal screening labs, as determined by the site physician.
• Subjects with suicidal ideation with intent or plan (indicated by affirmative answers to items 4 or 5 of the Suicidal Ideation section of the baseline C-SSRS) in the 6 months prior to screening or subjects who represent a significant risk of suicide in the opinion of the investigator.
• Presence or positive history of neurological illness, including seizures, mental retardation or any other disease/procedure/accident/intervention associated with significant injury to or malfunction of the central nervous system (CNS), or history of significant head injury.
• Metal implants, pacemaker, other metal (e.g., shrapnel or surgical prostheses) or paramagnetic objects contained within the body which may present a risk to the subject or interfere with the MR scan.
• Medicinal patch, unless removed prior to the MR scan
• Claustrophobia
• Currently taking any psychotropic medication, including antidepressant medications, benzodiazepines, antipsychotic medications, mood stabilizers, anti-epileptic medications, and stimulants. We will exclude any subject who requires treatment with any psychotropic medication from one of these classes.

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

New York State Psychiatric

New York, New York, 10023, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: The study will be subject and rater blind, i.e. subjects and raters, will be blinded to the treatment (ketamine dose) group. The study physician will be aware of the ketamine dose, and ketamine dose will be the same for both sessions. Subjects will not be told what the exact ketamine dose they will receive, but it will be based on their weight and will be no higher than 0.08 mg/kg.
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical Psychiatry

Model Details: Single blind (rater, participant will be unaware of dose). Subjects will be assigned ketamine doses in 10 subject cohorts

Study Record Dates

• First Submitted: October 13, 2020
• First Posted: October 19, 2020
• Study Start: January 1, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: February 3, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: after publication
• Access Criteria: Qualified reseaerchers

Locations

US (1)