Posttraumatic Stress DisorderPhase 2NCT05737693
Enhancing Week-long Psychological Treatment for PTSD With Ketamine
A Phase 2 study testing Ketamine and Midazolam in people with Posttraumatic Stress Disorder, run by Yale University at 2 sites in 2 countries.
Trial summary
The purpose of this study is to test if the combination of ketamine, vs midazolam, with an intensive trauma-focused psychotherapy will be more effective in relieving post-traumatic stress disorder (PTSD). Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Posttraumatic Stress Disorder
- What is being tested?
- Ketamine and Midazolam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 21 Aug 2023to 1 Aug 2031
- Phase
- Phase 2
- 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 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female between the ages of 21-70 years. This age range was chosen to fit with prior samples in which no adverse effects of ketamine have been observed. Adults in the 18-20 ranges have been eliminated because previous experience indicates that they often lack the maturity to participate effectively in similar protocols. Females will be included if they are not pregnant and agreed to utilize a medically accepted birth control method (to include oral, injectable, or implant birth control, condom, diaphragm with spermicide, intrauterine device, tubal ligation, abstinence, or partner with vasectomy) or if post-menopausal for at least 1 year, or surgically sterile.
- Must not have a medical/neurological problem or use medication that would render ketamine unsafe by history or medical evaluation.
- Diagnosis of chronic PTSD with a score of 25 or higher (i.e. severe PTSD) on the Clinician-Administered PTSD Scale (CAPS-5) at screening. PTSD symptoms must have persisted for >1 year post-trauma exposure to meet the DSM-5 definition of chronic.
- Subjects on FDA-approved antidepressant, trazodone, atypical neuroleptic, prazosin, or clonidine may enter the study if they have been on a stable treatment, as determined by the study clinician, for at least 4 weeks prior to randomization. Following randomization, small changes to doses may be allowable at the PI's discretion.
- Able to provide written informed consent.
- Able to read and write English.
Who cannot join
- Patients with a diagnostic history of borderline personality disorder, obsessive compulsive disorder, schizophrenia or schizoaffective disorder or currently exhibiting psychotic features as determined by the Structured Clinical Interview for DSM (SCID); dementia or suspicion thereof, are excluded. Patients with history of bipolar disorder will be included only if they have not experienced a manic or hypomanic episode in the 30 days prior to enrollment. Other DSM Axis I disorders are permitted as long as they are not considered primary disorders.
- Patients with a history of antidepressant-induced hypomania or mania as determined by open-ended psychiatric interview.
- Current, ongoing serious suicidal risk as assessed by evaluating investigator based on the Columbia-Suicide Severity Rating Scale (C-SSRS).
- Moderate severity or greater Substance Use Disorder (excepting Alcohol and Marijuana Use Disorder) during the 3 months prior to randomization, as determined by the SCID.Alcohol or Marijuana Use Disorder may be allowed based on the judgment of study physician/APRN/clinician that patients can remain sober for all study visits.
- Subjects on a prohibited medication (see Table 1). Patients will not be taken off medication for the purpose of this study.
- History of traumatic brain injury (TBI) with loss of consciousness for more than 24 hours or posttraumatic amnesia for more than 7 days may be considered if the trauma occurred more than 1 year ago, and no more than minimal symptoms have persisted over the past year.
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- Positive pregnancy test at screening or prior to any study drug infusion.
- Breathalyzer showing an alcohol level > 0% at screening, or at the discretion of the investigator, prior to any study drug infusion.
- Resting blood pressure lower than 90/60 or higher than 150/90, or resting heart rate lower than 45/min or higher than 100/min.
- Any significant history of serious medical or neurological illness.
- Any signs of major medical or neurological illness on examination or as a result of ECG screening or laboratory studies.
- Abnormality on physical examination. A subject with a clinical abnormality may be included only if the study physician considers the abnormality will not introduce additional risk factors and will not interfere with the study procedure.
- A positive pre-study (screening) urine drug screen or, at the study physician's discretion on any drug screens given before the scans.
- Pregnant or lactating women or a positive urine pregnancy test for women of child-bearing potential at screening or prior to any imaging day.
- Any history indicating learning disability or mental retardation.
- Known sensitivity to ketamine.
- Body circumference of 52 inches or greater.
- Body weight of 350 pounds or greater.
- History of claustrophobia.
- Presence of cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-MRI screening questionnaire.
- Donation of blood in excess of 500 mL within 56 days prior to dosing.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- Active engagement in trauma-focused CBT (TF cognitive-behavioral therapy) or any evidence-based PTSD psychotherapy (CPT, PE, EMDR) initiated within the past 3 months (continuation of established maintenance supportive therapy will be permitted
- Enrollment in another research study testing an experimental/clinical/behavioral intervention intended to affect symptoms initiated within the last 2 months, or intended enrollment within the next 3 months
- Table 1. Concomitant Treatments that are prohibited
- MAOIs: 4-weeks off medication prior to randomization is required.
- Memantine: 4-weeks of medication prior to randomization is required.
- Long Acting Benzodiazepines -Chlordiazepoxide, Diazepam, Flurazepam: 2-weeks off medication prior to randomization is required.
- Notes: As above, individuals who have used any of the prohibited medications within the "weeks off" time period will not be eligible for the study. Use of sedatives, hypnotics, benzodiazepines, sedating antihistamines or other psychotropic medications are not permitted within 8 hours of treatment sessions; except - at the discretion of the investigator - for medications that will result in discontinuation/withdrawal symptoms or that may alter the risk benefit ratio.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Yale University School of Medicine
New Haven, Connecticut, 06510
About this study
Official title: Posttraumatic Stress Disorder (PTSD) Treatment: Using Ketamine to Enhance Memory Reconsolidation and Extinction of Overgeneralized Fear in Individuals Diagnosed With PTSD
The purpose of this study is to test if the combination of ketamine, vs midazolam, with an intensive trauma-focused psychotherapy will be more effective in relieving post-traumatic stress disorder (PTSD). This week-long treatment has the potential to produce a significant therapeutic effect that otherwise would take months to occur. The study will also focus on learning about the neurophysiological changes produced by the proposed clinical trial.
Read the detailed description
Based on the current research findings on the therapeutic effectiveness of trauma focus psychotherapy and of ketamine combining the two treatments may yield a promising new rapid week-long treatment for PTSD. As PTSD symptoms' structure is comprised of several unique clusters which include re-experiencing, avoidance, depression and hypervigilance the investigators hypothesize that by combining Ketamine with trauma-focused psychotherapy the proposed intervention can address these PTSD symptoms clusters more effectively than existing treatments. This proposed clinical trial has the potential to produce a significant therapeutic effect that otherwise would take months to occur by tapping on the enhanced neuroplasticity and the antidepressant effect of ketamine (which lasts between 24hrs to 7 days), to promote rapid changes in learning and memory when applying psychotherapy within a unique "window of opportunity" of neurophysiological changes produced by the investigative drug.
During the first visit participants will undergo a clinical interview to establish a PTSD diagnosis and other eligibility criteria. If found eligible participants will be invited to take part in this 7-day rapid treatment trial for PTSD.
On the first therapy visits, participants will be educated about the psychological treatment that will be provided and the potential benefit of ketamine or midazolam that may enhance the psychotherapy outcomes.
On the second day of the study, participants will receive an infusion of ketamine or midazolam and will undergo a magnetic resonance imaging (MRI) to assess their brain reactivity to PTSD before the treatment.
On days 3-6 participants will attend a 60-90 minutes psychotherapy session to address their PTSD symptoms.
A second ketamine or midazolam infusion will take place on day 4 of the study to enhance the drug therapeutic effect for the study duration.
Day 7 will include another MRI scan to assess treatment effect on PTSD.
Participants will need to attend one follow up MRI scan and clinical evaluation at 30 days and then a clinical evaluation at 90 days post-treatment to assess the long-term effectiveness of the intervention.
- Conditions
- Posttraumatic Stress Disorder
- Keywords
- PTSD, ketamine, midazolam
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketalar
Week-long exposure therapy with ketamine infusion on day 2 and 4 of the psychotherapy
MidazolamDrug
Also called Versed
Week-long exposure therapy with midazolam infusion on day 2 and 4 of the psychotherapy
| Study group | Role | What they receive |
|---|---|---|
| 0.2mg/kg ketamine with psychotherapy | Experimental | Two infusions of low dose Ketamine combined with trauma-focused psychotherapy. Low dose ketamine infusion will take place on day 2 and day 4, of the psychotherapy intervention. A physician will oversee and administer the ketamine infusions. A nurse will accompany the subject throughout the study sessions, from the insertion of bilateral cannula for drug infusion and blood sampling, to the recovery following ketamine infusion. Whilst subjects undergo the infusion, their heart rate and blood pressure will be constantly monitored. The participant will receive a steady state of ketamine infusion of 0.2 mg/kg for 40 minutes. Receives: Drug: Ketamine |
| 0.5mg/kg ketamine with psychotherapy | Experimental | 2. Two infusions of Ketamine combined with trauma-focused psychotherapy. Low dose ketamine infusion will take place on day 2 and day 4, of the psychotherapy intervention. A physician will oversee and administer the ketamine infusions. A nurse will accompany the subject throughout the study sessions, from the insertion of bilateral cannula for drug infusion and blood sampling, to the recovery following ketamine infusion. Whilst subjects undergo the infusion, their heart rate and blood pressure will be constantly monitored. The participant will receive a steady state of ketamine infusion of 0.5 mg/kg for 40 minutes. Receives: Drug: Ketamine |
| Midazolam with psychotherapy | Active comparator | Midazolam combined with trauma-focused psychotherapy. Midazolam infusion procedure will take place on day 2 and day 4, of the psychotherapy intervention. A physician will oversee administer the Midazolam infusions. A nurse will accompany the subject throughout the study sessions, from the insertion of bilateral cannula for drug infusion and blood sampling, to the recovery following midazolam infusion. Whilst subjects undergo the infusion, their heart rate and blood pressure will be constantly monitored. The participant will receive a steady midazolam infusion at a rate 0.045 mg/kg for 40 minutes. Receives: Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amygdala activation to trauma memory (Phase 1; R61)
Phase 1 (R61) investigators will analyze the first 60 participants (20 per arm). Using MRI scan data, the investigators will compare changes in the amygdala bold activation from baseline to 30-day post treatment in response to the trauma scripts between the the 3 study arm. Greater activation of the amygdala is an indicator of a greater distress.
Investigators will also measure the effect size resulting from the mean changes in amygdala activation from pre to post treatment between each of the experimental groups and the active comparator to determine the dose that will be carried to phase 2.
Measured: Changes from baseline to 30-day post-treatment in amygdala activation to the trauma memory
To determine if ketamine + exposure therapy results in clinical improvement in PTSD symptoms which are significantly greater than midazolam + exposure therapy (Phase 2; combined R61/R33 data)
Change in PTSD symptoms from baseline up to 90-day post treatment. PTSD Symptoms severity will be evaluated overtime using PTSD Check List (PCL-5).
Evidence for the PCL suggests that 10 points difference in the measure is a reliable indicator for a clinically meaningful change. The PCL scores ranges from 0 (no symptoms) to a maximum score of 80 (PCL Score > 33 indicates probable PTSD diagnosis).
Measured: Baseline, 7 days, 30 days and 90 days
To determine if ketamine + exposure therapy results in more profound changes in task-based connectivity in region of interest than midazolam + exposure therapy (Phase 2; combined R61/R33 data)
Using MRI brain activation data, the investigators will compare changes in the connectivity between participants' different brain regions (brain network connectivity) from baseline to end of treatment and 30-day post treatment. Investigators will examine the neural connectivity between the amygdala, hippocampus, prefrontal cortex, striatum and insula and other major brain areas associated with PTSD.
Measured: Baseline, 7 days and 30 days (no MRI scan at 90 days post-treatment)
Secondary outcomes (2)
Change from baseline to 90 days post treatment in Beck Depression Inventory (BDI-II)
The self-report BDI-II will be used to assess severity of depressive symptoms. A higher score is associated with higher severity of depression. The score is interpreted as follows: 0-13 indicates minimal depression, 14-19 indicates mild depression, 20-28 indicates moderate depression and 29-63 indicates severe depression
Measured: Baseline, 7 days, 30 days and 90 days
Measure the changes in psychophysiological distress to trauma reminders as a result of the proposed intervention
Using wrist mobile galvanic skin responses (GSR) device the investigators will measure changes in GSR from pre to post treatment during exposure to avoidance cue. Investigators will compare the magnitude of these changes between the study arms. Higher GSR indicate a greater level of distress.
Measured: Baseline, 7 days and 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2023
- Study start21 Aug 2023
- Primary completion1 Aug 2030 (estimated)
- Study completion1 Aug 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Posttraumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Ilan Harpaz-Rotem, PhD ABPP, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05737693
- Sponsor's protocol ID
- 1509016530_a
- Other IDs
- R61MH129559
- Status last verified
- Aug 2026
- First submitted
- 1 Feb 2023
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Posttraumatic Stress Disorder (PTSD) Treatment: Using Ketamine to Enhance Memory Reconsolidation and Extinction of Overgeneralized Fear in Individuals Diagnosed With PTSD
- ClinicalTrials.gov ID
- NCT05737693
- Acronym / sponsor ID
- 1509016530_a
- Conditions
- Posttraumatic Stress Disorder
- Keywords
- PTSD, ketamine, midazolam
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 21 Aug 2023 (actual)
- Primary completion
- 1 Aug 2030 (estimated)
- Study completion
- 1 Aug 2031 (estimated)
- First posted
- 21 Feb 2023 (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.
The purpose of this study is to test if the combination of ketamine, vs midazolam, with an intensive trauma-focused psychotherapy will be more effective in relieving post-traumatic stress disorder (PTSD). This week-long treatment has the potential to produce a significant therapeutic effect that otherwise would take months to occur. The study will also focus on learning about the neurophysiological changes produced by the proposed clinical trial.
Detailed description
Based on the current research findings on the therapeutic effectiveness of trauma focus psychotherapy and of ketamine combining the two treatments may yield a promising new rapid week-long treatment for PTSD. As PTSD symptoms' structure is comprised of several unique clusters which include re-experiencing, avoidance, depression and hypervigilance the investigators hypothesize that by combining Ketamine with trauma-focused psychotherapy the proposed intervention can address these PTSD symptoms clusters more effectively than existing treatments. This proposed clinical trial has the potential to produce a significant therapeutic effect that otherwise would take months to occur by tapping on the enhanced neuroplasticity and the antidepressant effect of ketamine (which lasts between 24hrs to 7 days), to promote rapid changes in learning and memory when applying psychotherapy within a unique "window of opportunity" of neurophysiological changes produced by the investigative drug.
During the first visit participants will undergo a clinical interview to establish a PTSD diagnosis and other eligibility criteria. If found eligible participants will be invited to take part in this 7-day rapid treatment trial for PTSD.
On the first therapy visits, participants will be educated about the psychological treatment that will be provided and the potential benefit of ketamine or midazolam that may enhance the psychotherapy outcomes.
On the second day of the study, participants will receive an infusion of ketamine or midazolam and will undergo a magnetic resonance imaging (MRI) to assess their brain reactivity to PTSD before the treatment.
On days 3-6 participants will attend a 60-90 minutes psychotherapy session to address their PTSD symptoms.
A second ketamine or midazolam infusion will take place on day 4 of the study to enhance the drug therapeutic effect for the study duration.
Day 7 will include another MRI scan to assess treatment effect on PTSD.
Participants will need to attend one follow up MRI scan and clinical evaluation at 30 days and then a clinical evaluation at 90 days post-treatment to assess the long-term effectiveness of the intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 0.2mg/kg ketamine with psychotherapy | Experimental | Drug: KetamineTwo infusions of low dose Ketamine combined with trauma-focused psychotherapy. Low dose ketamine infusion will take place on day 2 and day 4, of the psychotherapy intervention. A physician will oversee and administer the ketamine infusions. A nurse will accompany the subject throughout the study sessions, from the insertion of bilateral cannula for drug infusion and blood sampling, to the recovery following ketamine infusion. Whilst subjects undergo the infusion, their heart rate and blood pressure will be constantly monitored. The participant will receive a steady state of ketamine infusion of 0.2 mg/kg for 40 minutes. |
| 0.5mg/kg ketamine with psychotherapy | Experimental | Drug: Ketamine2. Two infusions of Ketamine combined with trauma-focused psychotherapy. Low dose ketamine infusion will take place on day 2 and day 4, of the psychotherapy intervention. A physician will oversee and administer the ketamine infusions. A nurse will accompany the subject throughout the study sessions, from the insertion of bilateral cannula for drug infusion and blood sampling, to the recovery following ketamine infusion. Whilst subjects undergo the infusion, their heart rate and blood pressure will be constantly monitored. The participant will receive a steady state of ketamine infusion of 0.5 mg/kg for 40 minutes. |
| Midazolam with psychotherapy | Active comparator | Drug: MidazolamMidazolam combined with trauma-focused psychotherapy. Midazolam infusion procedure will take place on day 2 and day 4, of the psychotherapy intervention. A physician will oversee administer the Midazolam infusions. A nurse will accompany the subject throughout the study sessions, from the insertion of bilateral cannula for drug infusion and blood sampling, to the recovery following midazolam infusion. Whilst subjects undergo the infusion, their heart rate and blood pressure will be constantly monitored. The participant will receive a steady midazolam infusion at a rate 0.045 mg/kg for 40 minutes. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female between the ages of 21-70 years. This age range was chosen to fit with prior samples in which no adverse effects of ketamine have been observed. Adults in the 18-20 ranges have been eliminated because previous experience indicates that they often lack the maturity to participate effectively in similar protocols. Females will be included if they are not pregnant and agreed to utilize a medically accepted birth control method (to include oral, injectable, or implant birth control, condom, diaphragm with spermicide, intrauterine device, tubal ligation, abstinence, or partner with vasectomy) or if post-menopausal for at least 1 year, or surgically sterile.
- Must not have a medical/neurological problem or use medication that would render ketamine unsafe by history or medical evaluation.
- Diagnosis of chronic PTSD with a score of 25 or higher (i.e. severe PTSD) on the Clinician-Administered PTSD Scale (CAPS-5) at screening. PTSD symptoms must have persisted for >1 year post-trauma exposure to meet the DSM-5 definition of chronic.
- Subjects on FDA-approved antidepressant, trazodone, atypical neuroleptic, prazosin, or clonidine may enter the study if they have been on a stable treatment, as determined by the study clinician, for at least 4 weeks prior to randomization. Following randomization, small changes to doses may be allowable at the PI's discretion.
- Able to provide written informed consent.
Key exclusion criteria (29 listed)
- Patients with a diagnostic history of borderline personality disorder, obsessive compulsive disorder, schizophrenia or schizoaffective disorder or currently exhibiting psychotic features as determined by the Structured Clinical Interview for DSM (SCID); dementia or suspicion thereof, are excluded. Patients with history of bipolar disorder will be included only if they have not experienced a manic or hypomanic episode in the 30 days prior to enrollment. Other DSM Axis I disorders are permitted as long as they are not considered primary disorders.
- Patients with a history of antidepressant-induced hypomania or mania as determined by open-ended psychiatric interview.
- Current, ongoing serious suicidal risk as assessed by evaluating investigator based on the Columbia-Suicide Severity Rating Scale (C-SSRS).
- Moderate severity or greater Substance Use Disorder (excepting Alcohol and Marijuana Use Disorder) during the 3 months prior to randomization, as determined by the SCID.Alcohol or Marijuana Use Disorder may be allowed based on the judgment of study physician/APRN/clinician that patients can remain sober for all study visits.
- Subjects on a prohibited medication (see Table 1). Patients will not be taken off medication for the purpose of this study.
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 |
|---|---|---|
| KetamineAlso: KetalarWeek-long exposure therapy with ketamine infusion on day 2 and 4 of the psychotherapy | Drug | 0.2mg/kg ketamine with psychotherapy, 0.5mg/kg ketamine with psychotherapy |
| MidazolamAlso: VersedWeek-long exposure therapy with midazolam infusion on day 2 and 4 of the psychotherapy | Drug | Midazolam with psychotherapy |
Primary outcome
Amygdala activation to trauma memory (Phase 1; R61)
Time frame: Changes from baseline to 30-day post-treatment in amygdala activation to the trauma memory
Phase 1 (R61) investigators will analyze the first 60 participants (20 per arm). Using MRI scan data, the investigators will compare changes in the amygdala bold activation from baseline to 30-day post treatment in response to the trauma scripts between the the 3 study arm. Greater activation of the amygdala is an indicator of a greater distress. Investigators will also measure the effect size resulting from the mean changes in amygdala activation from pre to post treatment between each of the experimental groups and the active comparator to determine the dose that will be carried to phase 2.
To determine if ketamine + exposure therapy results in clinical improvement in PTSD symptoms which are significantly greater than midazolam + exposure therapy (Phase 2; combined R61/R33 data)
Time frame: Baseline, 7 days, 30 days and 90 days
Change in PTSD symptoms from baseline up to 90-day post treatment. PTSD Symptoms severity will be evaluated overtime using PTSD Check List (PCL-5). Evidence for the PCL suggests that 10 points difference in the measure is a reliable indicator for a clinically meaningful change. The PCL scores ranges from 0 (no symptoms) to a maximum score of 80 (PCL Score > 33 indicates probable PTSD diagnosis).
To determine if ketamine + exposure therapy results in more profound changes in task-based connectivity in region of interest than midazolam + exposure therapy (Phase 2; combined R61/R33 data)
Time frame: Baseline, 7 days and 30 days (no MRI scan at 90 days post-treatment)
Using MRI brain activation data, the investigators will compare changes in the connectivity between participants' different brain regions (brain network connectivity) from baseline to end of treatment and 30-day post treatment. Investigators will examine the neural connectivity between the amygdala, hippocampus, prefrontal cortex, striatum and insula and other major brain areas associated with PTSD.
2 secondary outcomes
Change from baseline to 90 days post treatment in Beck Depression Inventory (BDI-II)
Time frame: Baseline, 7 days, 30 days and 90 days
Measure the changes in psychophysiological distress to trauma reminders as a result of the proposed intervention
Time frame: Baseline, 7 days and 30 days
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 24 Aug 2026.
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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. This study is not recruiting at the moment.
Ilan Harpaz-Rotem, PhD ABPP principal investigator
Yale University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketamine and Midazolam in people with Posttraumatic Stress Disorder, run by Yale University at 2 sites in 2 countries.
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 6 inclusion and 29 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: under way, not looking for participants, as of the sponsor's last update on 24 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 2 sites in United States, Israel. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amygdala activation to trauma memory (Phase 1; R61) (time frame: Changes from baseline to 30-day post-treatment in amygdala activation to the trauma memory). The study lists 3 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 24 Aug 2026.