HealthyPhase 1NCT05401227
Glutamatergic Mechanisms: Aim2
A Phase 1 study testing Ketamine and Ts-134 or XT in people with Healthy, run by New York State Psychiatric Institute at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Ketamine and Ts-134 or XT
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2022to Aug 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
- Pregnancy or breast-feeding. This exclusion criterion applies only to females of child-bearing potential (not surgically sterilized and between menarche and 1 year postmenopausal). Must test negative for pregnancy at the time of screening based on a serum pregnancy test.
- 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).
Show all 18Show fewer
- 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.
- Any material in the body that is a contraindication for MRI procedures
- Currently taking any psychotropic medication, including antidepressant medications, benzodiazepines, antipsychotic medications, mood stabilizers, anti-epileptic medications, and stimulants. We will exclude any participant who requires treatment with any psychotropic medication from one of these classes.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
NYSPI
New York, New York, 10032
Joshua Kantrowitz, MD
About this study
Official title: Glutamatergic Mechanisms of Psychosis and Target Engagement: Aim2
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.
Read the detailed description
Schizophrenia (Sz) is associated with psychotic symptoms, such as hearing voices and paranoid beliefs that remain partially or fully refractory to standard antipsychotic medications for ~2/3 of patients. Alternative, glutamatergic approaches for treatment development have been proposed but have not yet led to FDA-approved medications. Moreover, several glutamate-targeted medications, such as pomaglumetad (POMA), have failed in pivotal clinical trials despite robust effectiveness in preclinical models. A major barrier to effective glutamatergic treatment development is the absence of validated measures for target engagement that can identify effective compounds and guide dose selection. Target" refers to a factor that an intervention is intended to modify, leading to improvement in symptoms, and target engagement biomarkers are a measure of the ability of the intervention to "engage" the target.
As part of the recently completed NIMH multicenter FAST-PS initiative and a parallel industry sponsored project, we evaluated ketamine-induced pharmacoBOLD (phBOLD) in healthy volunteers (HV) as a potential target engagement biomarker for development of metabotropic glutamate (mGluR2/3) agonists, as a prelude to planned studies in Sz. BOLD imaging indirectly measures brain energy, as a proxy for glutamate target engagement.
The structure of the R01 grant funding this protocol was split into three studies, specific aim (SA) 1, 2 and 3. In FAST-PS, a high dose of ketamine (0.23 mg/kg) was used in order to produce robust pharmacological effects.
Under SA1, which was conducted under IRB 8063, this dose was titrated downward in across two phBOLD sessions in HV in order to determine the lowest dose of ketamine that still produces a phBOLD response of Cohen's d≥1.5, hypothesizing that this dose would provide the best signal to noise for use in SA2. The study was conducted in groups of 10 subject per dose cohort, and the analysis supports using a low dose of 0.086 mg/kg for SA2.
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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Ketamine during an MRI
Ts-134 or XTDrug
4 days of TS-134 20 mg (1st 20 subjects )or XT (last 100 subjects)
PlaceboDrug
4 days of placebo
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Ketamine; Drug: Ts-134 or XT |
| High ketamine, placebo | Placebo comparator | Two administrations of ketamine 0.23 mg/kg pre post 4 days of placebo Receives: 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 Receives: Drug: Ketamine; Drug: Ts-134 or XT |
| Medium Ketamine, placebo | Placebo comparator | Two administrations of ketamine 0.125 mg/kg pre post 4 days of placebo Receives: 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 Receives: Drug: Ketamine; Drug: Ts-134 or XT |
| Low Ketamine, placebo | Placebo comparator | Two administrations of ketamine 0.06 mg/kg pre post 4 days of placebo Receives: Drug: Ketamine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 or XT
Measured: Baseline and Day 4
Brief Psychiatric Rating Scale (BPRS)
Changes in BPRS scores following administrations of TS-134 or XT
Measured: Baseline and Day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2022
- Study start15 Oct 2022
- Primary completionAug 2028 (estimated)
- Study completionAug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Joshua Kantrowitz, New York State Psychiatric Institute
- Investigators
- Joshua Kantrowitz, MD, Principal investigator, NYSPI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05401227
- Sponsor's protocol ID
- 8299
- Status last verified
- Aug 2026
- First submitted
- 27 May 2022
- Last updated
- 17 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NIMH Data archive
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glutamatergic Mechanisms of Psychosis and Target Engagement: Aim2
- ClinicalTrials.gov ID
- NCT05401227
- Acronym / sponsor ID
- 8299
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 15 Oct 2022 (actual)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Aug 2029 (estimated)
- First posted
- 2 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Schizophrenia (Sz) is associated with psychotic symptoms, such as hearing voices and paranoid beliefs that remain partially or fully refractory to standard antipsychotic medications for ~2/3 of patients. Alternative, glutamatergic approaches for treatment development have been proposed but have not yet led to FDA-approved medications. Moreover, several glutamate-targeted medications, such as pomaglumetad (POMA), have failed in pivotal clinical trials despite robust effectiveness in preclinical models. A major barrier to effective glutamatergic treatment development is the absence of validated measures for target engagement that can identify effective compounds and guide dose selection. Target" refers to a factor that an intervention is intended to modify, leading to improvement in symptoms, and target engagement biomarkers are a measure of the ability of the intervention to "engage" the target.
As part of the recently completed NIMH multicenter FAST-PS initiative and a parallel industry sponsored project, we evaluated ketamine-induced pharmacoBOLD (phBOLD) in healthy volunteers (HV) as a potential target engagement biomarker for development of metabotropic glutamate (mGluR2/3) agonists, as a prelude to planned studies in Sz. BOLD imaging indirectly measures brain energy, as a proxy for glutamate target engagement.
The structure of the R01 grant funding this protocol was split into three studies, specific aim (SA) 1, 2 and 3. In FAST-PS, a high dose of ketamine (0.23 mg/kg) was used in order to produce robust pharmacological effects.
Under SA1, which was conducted under IRB 8063, this dose was titrated downward in across two phBOLD sessions in HV in order to determine the lowest dose of ketamine that still produces a phBOLD response of Cohen's d≥1.5, hypothesizing that this dose would provide the best signal to noise for use in SA2. The study was conducted in groups of 10 subject per dose cohort, and the analysis supports using a low dose of 0.086 mg/kg for SA2.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 6
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| High Ketamine, TS-134 (first 20 subjects) or XT (remaining 100 subjects) | Experimental | Drug: Ketamine, Drug: Ts-134 or XTTwo administrations of ketamine 0.23 mg/kg pre post 4 days of TS-134 or XT |
| High ketamine, placebo | Placebo comparator | Drug: Ketamine, Drug: PlaceboTwo administrations of ketamine 0.23 mg/kg pre post 4 days of placebo |
| Medium Ketamine, TS-134 (first 20 subjects) or XT (remaining 100 subjects) | Experimental | Drug: Ketamine, Drug: Ts-134 or XTTwo administrations of ketamine 0.125 mg/kg pre post 4 days of TS-134 or XT |
| Medium Ketamine, placebo | Placebo comparator | Drug: Ketamine, Drug: PlaceboTwo administrations of ketamine 0.125 mg/kg pre post 4 days of placebo |
| Low Ketamine, TS-134 (first 20 subjects) or XT (remaining 100 subjects) | Experimental | Drug: Ketamine, Drug: Ts-134 or XTTwo administrations of ketamine 0.086 mg/kg pre post 4 days of TS-134 or XT |
| Low Ketamine, placebo | Placebo comparator | Drug: Ketamine, Drug: PlaceboTwo administrations of ketamine 0.06 mg/kg pre post 4 days of placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (18 listed)
- 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
- Pregnancy or breast-feeding. This exclusion criterion applies only to females of child-bearing potential (not surgically sterilized and between menarche and 1 year postmenopausal). Must test negative for pregnancy at the time of screening based on a serum pregnancy test.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineKetamine during an MRI | Drug | 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 |
| Ts-134 or XT4 days of TS-134 20 mg (1st 20 subjects )or XT (last 100 subjects) | Drug | 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) |
| Placebo4 days of placebo | Drug | High ketamine, placebo, Low Ketamine, placebo, Medium Ketamine, placebo |
Primary outcome
Final PharmacoBOLD signals in pre-specified ROIs
Time frame: Baseline and Day 4
Changes in ketamine-induced PharmacoBOLD fMRI signals in pre-specified ROIs (anterior cingulate cortex) following administrations of TS-134 or XT
Brief Psychiatric Rating Scale (BPRS)
Time frame: Baseline and Day 4
Changes in BPRS scores following administrations of TS-134 or XT
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2026.
- Individual participant dataSharing planned: Yes. NIMH Data archive
Related trials for Healthy
Enrolling by invitationObservational study
Connors Protocol for the Management and Use of Stored Human Specimens (Stored Human Specimens)
Healthy Volunteer Samples
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
Recruiting
Effects of Urolithin A Supplementation on Glucose Metabolism in Healthy Adults 55 >= Years Old: A Randomized Triple-Masked Controlled Clinical Trial
Healthy Volunteer
Not yet recruitingObservational study
Assessing the Impact of Perceptions of Unpredictability on Objective Measures of Food Consumption and Metabolism
Healthy Volunteer, Obestity
Not yet recruitingPhase 1
Phase I Trial of High-Density Theta Burst Stimulation (hdTBS)
Healthy Volunteers
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Joshua Kantrowitz, MD principal investigator
NYSPI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ketamine and Ts-134 or XT in people with Healthy, run by New York State Psychiatric Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Joshua Kantrowitz (6467748477, joshua.kantrowitz@nyspi.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Final PharmacoBOLD signals in pre-specified ROIs (time frame: Baseline and Day 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026; AzTrials last refreshed its copy on 2 Nov 2026.