Glutamatergic Mechanisms: Aim2

NCT05401227 | Suspended Phase 1 DMC FDA Drug

• 1 other identifier: 8299
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

In the present study, 120 healthy volunteers (HV) will be randomized to one of three ketamine-induced pharmacoBOLD (phBOLD) arms: low, medium, and high. Within each ketamine arm, participants will be randomized to 4 days of "study drug" \[TS-134 (1st 20 participants) or XT (remaining 100 participants)\] or placebo in a 5:3 ratio (25 study drug:15 placebo per arm). During the study, each participant will undergo a Screening Period (up to 31 days), a 4-day Treatment Period, and a total of two phBOLD sessions: a first session at Baseline and a second session on Day 4 of the Treatment Period, conducted at least 7 days apart, and a follow up visit.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• Final PharmacoBOLD signals in pre-specified ROIs

  Changes in ketamine-induced PharmacoBOLD fMRI signals in pre-specified ROIs (anterior cingulate cortex) following administrations of TS-134

  Baseline and Day 4

• Brief Psychiatric Rating Scale (BPRS)

  Changes in BPRS scores following administrations of TS-134

  Baseline and Day 4

Study Arms (6)

High Ketamine, TS-134 (first 20 subjects) or XT (remaining 100 subjects)

EXPERIMENTAL

Two administrations of ketamine 0.23 mg/kg pre post 4 days of TS-134 or XT

Drug: Ketamine; Drug: Ts-134

High ketamine, placebo

PLACEBO COMPARATOR

Two administrations of ketamine 0.23 mg/kg pre post 4 days of placebo

Drug: Ketamine; Drug: Placebo

Medium Ketamine, TS-134 (first 20 subjects) or XT (remaining 100 subjects)

EXPERIMENTAL

Two administrations of ketamine 0.125 mg/kg pre post 4 days of TS-134 or XT

Drug: Ketamine; Drug: Ts-134

Medium Ketamine, placebo

PLACEBO COMPARATOR

Two administrations of ketamine 0.125 mg/kg pre post 4 days of placebo

Drug: Ketamine; Drug: Placebo

Low Ketamine, TS-134 (first 20 subjects) or XT (remaining 100 subjects)

EXPERIMENTAL

Two administrations of ketamine 0.086 mg/kg pre post 4 days of TS-134 or XT

Drug: Ketamine; Drug: Ts-134

Low Ketamine, placebo

PLACEBO COMPARATOR

Two administrations of ketamine 0.06 mg/kg pre post 4 days of placebo

Drug: Ketamine; Drug: Placebo

Interventions

Ts-134 DRUG

4 days of TS-134 20 mg

High Ketamine, TS-134 (first 20 subjects) or XT (remaining 100 subjects); Low Ketamine, TS-134 (first 20 subjects) or XT (remaining 100 subjects); Medium Ketamine, TS-134 (first 20 subjects) or XT (remaining 100 subjects)

Placebo DRUG

4 days of placebo TS-134

High ketamine, placebo; Low Ketamine, placebo; Medium Ketamine, placebo

Ketamine DRUG

Ketamine during an MRI

High Ketamine, TS-134 (first 20 subjects) or XT (remaining 100 subjects); High ketamine, placebo; Low Ketamine, TS-134 (first 20 subjects) or XT (remaining 100 subjects); Low Ketamine, placebo; Medium Ketamine, TS-134 (first 20 subjects) or XT (remaining 100 subjects); Medium Ketamine, placebo

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 at screen
• Medically healthy, as assessed by study physician at screen
• 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 (See section 5.3) during the study. Women who are post-menopausal or otherwise not of childbearing potential are also eligible.
• Willing and reliable to participate in XT or placebo phase as an outpatient and/or agreeable to participate as an inpatient.

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) as assessed at screen
• Positive urine toxicology or alcohol at screen
• History of recreational ketamine use, recreational PCP use, or an adverse reaction to ketamine. Participants who have participated in prior research ketamine studies will be eligible. Participants can have infusions not more frequently than biweekly, and not more than 1/month on average, therefore participants 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 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 at screen, including:
• Contraindications to XT (urinary retention, moderate or severe hepatic impairment, gastric retention, untreated narrow-angle glaucoma, hypernasality)
• renal problems (GFR\<60)
• high blood pressure (defined as supine systolic blood pressure (SBP) \> 140 or supine diastolic blood pressure (DBP) \> 90)
• low blood pressure (defined as supine SBP \< 100, DBP \< 60)
• abnormal orthostatic blood pressure (change in mean arterial pressure \[1/3 systolic + 2/3 diastolic\] of \> 20% between supine and standing blood pressures)
• clinically significant cardiac illness, as determined by the site physician
• clinically significant abnormal screening labs, as determined by the site physician
• Participants 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 participants 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.

Sponsors & Collaborators

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

Study Sites (1)

NYSPI

New York, New York, 10032, United States

Location

MeSH Terms

Interventions

Ketamine

Intervention Hierarchy (Ancestors)

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

Study Officials

• Joshua Kantrowitz, MD

  NYSPI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist

Model Details: For the remaining 100 subjects will be randomized to one of three ketamine arms. with in each ketamine arm, subjects will be randomized to XT or placebo for 6 total arms. The first 20 received TS-134 or placebo.

Study Record Dates

• First Submitted: May 27, 2022
• First Posted: June 2, 2022
• Study Start: October 15, 2022
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: April 13, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Per NIMH Data archive regulations
• Access Criteria: Qualified investigator

Locations

US (1)