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Post Traumatic Stress Disorder PTSDPhase 1/2NCT06795659

Combining Esketamine and Prolonged Exposure Treatment for PTSD (Post Traumatic Stress Disorder)

A Phase 1/2 study testing Esketamine (Intranasal Spray) and Massed Prolonged Exposure (PE) in people with Post Traumatic Stress Disorder PTSD, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is being done to see if Prolonged Exposure (PE), a well-researched, very effective individual (one-to-one) behavioral therapy designed to help people to directly deal with traumatic events they have suffered in the past, can be combined with intranasal esketamine (ketamine) for the treatment of… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Post Traumatic Stress Disorder PTSD
What is being tested?
Esketamine (Intranasal Spray) and Massed Prolonged Exposure (PE)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
9 Jun 2025to 16 Jan 2026
Phase
Phase 1/2
Are there results?
None posted in the registry

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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Individual between the ages of 18-65 years old (Young adults [18 to 24 years old] must not be taking an antidepressant).
  • PTSD diagnosis as assessed by Clinician-Administered Posttraumatic Stress Scale (CAPS-5)
  • Able to speak and read English (due to standardization of outcome measures)
  • On stable doses of current medications for at least 4 weeks
  • Weigh between 50-100 kg (110-220 pounds).

Who cannot join

  • Young adults (18-24) currently taking any antidepressant.
  • Lifetime history of psychotic disorder or history of significant psychotic symptoms.
  • Lifetime history of manic episode.
  • Moderate or greater severity for alcohol or substance use disorder (DSM-5) in the previous six months.
  • A history of ketamine or phencyclidine abuse.
  • Evidence of a traumatic brain injury severe enough to interfere with comprehension and responding to the baseline screening questionnaires.
Show all 19Show fewer
  • Current suicidal ideation severe enough to warrant immediate attention (as determined by the Depressive Symptoms Index-Suicidality Subscale and corroborated by a clinical risk assessment by a credentialed provider)
  • Other psychiatric disorders severe enough to warrant designation as the primary disorder as determined by clinician judgment.
  • Current use (with past 4 weeks) of any prohibited concomitant medications
  • Benzodiazepines, other medications, sedatives, acute alcohol use, or recreational drug use that would put patients at risk in the judgment of clinical providers).
  • Planned use of ketamine (i.e., for pain control) or participation in another trauma-focused psychotherapy during the time of the study.
  • Uncontrolled hypertension or tachycardia
  • A history of sensitivity or adverse reaction to ketamine or its excipients
  • An unstable medical, cardiovascular, pulmonary, or neurological condition that the investigator considers a contraindication to ketamine administration
  • Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation.
  • Intracerebral hemorrhage.
  • Pregnancy or breastfeeding; women of childbearing potential unwilling to utilize reliable methods of contraception
  • History of nasal surgery or nasal obstructions experienced as an adult.
  • Inability to arrange for assisted transportation on ketamine treatment days due to recommendation that patient not drive for the remainder of the day following a ketamine treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: Combining Esketamine and Prolonged Exposure for PTSD: A Proof-of-Concept Clinical Trial

This study is being done to see if Prolonged Exposure (PE), a well-researched, very effective individual (one-to-one) behavioral therapy designed to help people to directly deal with traumatic events they have suffered in the past, can be combined with intranasal esketamine (ketamine) for the treatment of posttraumatic stress disorder (PTSD) to enhance treatment benefits. Ketamine nasal spray is a drug approved by the U.S. Food \& Drug Administration (FDA) for treatment resistant depression. Combined with PE, intranasal ketamine may help to augment PE and further reduce participants' PTSD symptoms.

Read the detailed description

The study is an early phase II, open label, proof of concept, pilot clinical trial to explore the feasibility, acceptability, and effects of esketamine combined with PE in individuals seeking treatment for PTSD. All individuals will complete a phone screen to learn more about the study to discuss broad eligibility criteria. Study candidates will be recruited from provider referrals across the San Antonio community as well as from self-referrals. Interested individuals who appear to meet initial eligibility will be consented and the complete a baseline assessment to determine study eligibility. Eligible participants will be enrolled to receive 10 sessions of PE delivered in massed (daily) format over 2 weeks (weekdays, not including weekends and holidays). Participants will also receive intranasal esketamine six times over a 2-week period (three times a week) approximately 1 hour after PE sessions 1, 3, 5, 6, 8, and 10 over this time period.

Being tested
Esketamine (Intranasal Spray), Massed Prolonged Exposure (PE)
Keywords
Massed Prolonged Exposure, Esketamine
Medical subject headings
Combat Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Esketamine (Intranasal Spray)Drug

    Esketamine doses will be administered via insufflation with a starting dose of 1 spray of 14 mg per nostril (28 mg/total). Based on tolerability, total dose will be increased to a target dose of 84 mg delivered as three bouts separated by 5 minutes per bout (total dose administered in 15 minutes).

  • Massed Prolonged Exposure (PE)Behavioural

    Eligible participants will be enrolled to receive 10 sessions of PE delivered in massed (daily) format over 2 weeks (weekdays, not including weekends and holidays)

Study groups in NCT06795659
Study groupRoleWhat they receive
Esketamine combined with Prolonged Exposure for PTSDExperimentalEsketamine (intranasal ketamine) will be administered 6 times over a 2-week period after administering PE sessions
Receives: Drug: Esketamine (Intranasal Spray); Behavioral: Massed Prolonged Exposure (PE)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Feasibility of Treatment using Esketamine and PE

    Number of eligible referrals

    Measured: Study start to closing to enrollment (approximately 12 months)

  2. Satisfaction with Therapy and Therapist Scale - Revised (STTS-R)

    A12-item self-report measure with strong psychometric properties used to assess the patient's satisfaction with the therapy provided and the therapist. Even number items assess satisfaction with therapy and odd number items assess satisfaction with therapist. Scores can range from 12-60. Higher scores are reflective of greater satisfaction. Items are on a 5-point Likert scale that ranges from 1 = "Strong disagree" to 5 = "Strongly Agree'. Additionally, a 13th item provides an independent assessment of the patient's global improvement. The STTS-R will be administered at the final treatment session and at the 1-month follow-up assessments.

    Measured: Day 1 to 1 month

  3. Enrollment proportion

    Proportion of eligible participants

    Measured: Study start to closed to enrollment (approximately 12 months)

  4. Adherence to treatment

    Number of participants that adhered to and completed treatment

    Measured: Study start to closed to enrollment (approximately 12 months)

  5. CEQ for Esketamine (Expectancy Score)

    The esketamine treatment will be rated as credible with positive expected treatment benefits on the Credibility and Expectancy Questionnaire. Responses to four questions are scored using a 9-point Likert scale (1= not at all, 9= extremely). Responses to two of the questions are scored using an 11-point Likert Scale (0% to 100%). The combined responses are used to generate a score for expectancy.

    Measured: Day 1 to 1 month

  6. CEQ for Esketamine (Credibility Score)

    The esketamine treatment will be rated as credible with positive expected treatment benefits on the Credibility and Expectancy Questionnaire. Responses to four questions are scored using a 9-point Likert scale (1= not at all, 9= extremely). Responses to two of the questions are scored using an 11-point Likert Scale (0% to 100%). The combined responses are used to generate a score for credibility.

    Measured: Day 1 to 1 month

  7. CEQ for PE (Credibility score)

    The CEQ for PE is a 6-item measure that was designed to assess treatment expectancy and rationale credibility for use in clinical outcomes studies. Responses to four questions are scored using a 9-point Likert scale (1= not at all, 9= extremely). Responses to two of the questions are scored using an 11-point Likert Scale (0% to 100%). The responses are used to generate a score for credibility.

    Measured: Day 1 to 1 month

  8. CEQ for PE (Expectancy score)

    The CEQ for PE is a 6-item measure that was designed to assess treatment expectancy and rationale credibility for use in clinical outcomes studies. Responses to four questions are scored using a 9-point Likert scale (1= not at all, 9= extremely). Responses to two of the questions are scored using an 11-point Likert Scale (0% to 100%). The responses are used to generate a score for expectancy.

    Measured: Day 1 to 1 month

  9. Post Traumatic Stress Disorder (PTSD) (PCL-5) Checklist-5 Change in Score

    A 20-item self-report measure designed to assess PSTSD symptoms as defined by the DSM-5 and evaluates how much participants have been bothered by these symptoms in the past week (for all assessments during treatment and one week follow-up) or the past month (all other assessment time points) because of a specific life event. Each item of the PCL-5 is scored on a five-point scale ranging from 0 ("Not at all") to 4 ("Extremely). Scores can range from 0-80. Scores ≥ 33 indicate clinically elevated PTSD symptoms.

    Measured: Baseline to 1 month

  10. The Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (CAPS-5)

    The CAPS-5 is a structured interview that assesses the DSM-5 criteria for PTSD. Each item is rated on a severity scale ranging from 0 (Absent) to 4 (Extreme/Incapacitating) and combines information about frequency and intensity for each of the 20 symptoms. Additional items evaluate overall symptom duration, distress, impairment, dissociative symptoms, and global ratings by the interviewer. Subscale scores are calculated by summing severity scores for items in the following PTSD symptom clusters: re-experiencing, avoidance, negative alterations in cognitions and mood, and hyperarousal. Scores ≥ 25 indicate a probable diagnosis of PTSD.

    Measured: Baseline to 1 month

Secondary outcomes (5)

  1. Depressive Symptom Index - Suicidality Subscale (DSI-SS)

    The DSI-SS is a 4-item self-report measure of suicidal ideation that focuses on ideation, plans, perceived control over ideation, and impulses for suicide. Scores on each item range from 0 to 3, with higher scores reflecting greater severity of suicidal ideation. Possible range of scores is from 0-36.

    Measured: Baseline to 1 month

  2. Generalized Anxiety Disorder Screener

    This is a 7-item measure that asks participants to rate the frequency with which they have been bothered by anxiety symptoms within the past 2 weeks on a scale ranging from 0 ("not at all") to 3 ("nearly every day"). Possible scores range from 0-21. Scores on all items are summed to obtain a total severity score. Scores reflect no significant anxiety symptoms (0-4), mild anxiety symptoms (5-9), moderate anxiety symptoms (10-14), and severe anxiety symptoms (>15).

    Measured: Baseline to 1 month

  3. Patient Health Questionnaire-9

    It consists of 9 items that assess both affective and somatic symptoms related to depression and depressive disorders; these 9 items correspond to the diagnostic criteria for Major Depressive Disorder. Respondents rate the frequency with which they have been bothered by depressive symptoms within the past 2 weeks (baseline and 1-month follow-up) or 1 week (during treatment and 1-week follow-up) on a scale ranging from 0 ("not at all") to 3 ("nearly every day"). Scores on all items are summed to obtain a total severity score. Scores range from 0-27. Scores reflect no significant depressive symptoms (0-4), mild depressive symptoms (5-9), moderate depressive symptoms (10-14), moderately severe depressive symptoms (15-19), and severe depressive symptoms (>19).

    Measured: Baseline to 1 month

  4. Posttraumatic Cognitions Inventory (PTCI)

    The PTCI is a 36-item self-report questionnaire that measures trauma-related thoughts and beliefs. Participants rate their agreement or disagreement with each statement on a 7-point scale, with 1 meaning "totally disagree" and 7 meaning "totally agree". Higher scores indicate a greater endorsement of negative posttraumatic cognitions. Scores range from 36-252.

    The PTCI has three subscales:

    Negative Cognitions of the Self: 21 items (7-63 possible range of score) Negative Cognitions of the World: 7 items (7-49 possible range of score) Self-Blame for the traumatic event: 5 items (7-35 possible range of score)

    Measured: Baseline to 1 month

  5. Brief Inventory of Psychosocial Functioning

    A 7-item self-report instrument measuring respondents' level of functioning in seven life domains: romantic relationship, relationship with children, family relationships, friendships and socializing, work, training and education, and activities of daily living. Respondents indicate the degree to which they had trouble in the last 30 days in each area on a 7-point scale ranging from 0 ("Not at all") to 6 ("Very much"). Possible scores range from 0-42, with a higher score indicating better psychosocial functioning.

    Measured: Baseline to 1 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2025
  2. Study start9 Jun 2025
  3. Primary completion16 Jan 2026
  4. Study completion16 Jan 2026

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Open-label, proof-of-concept, pilot trial
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06795659
Sponsor's protocol ID
STUDY00001076
Status last verified
Jan 2026
First submitted
21 Jan 2025
Last updated
28 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Presentations and publications produced as a result of this work will follow the STRONG STAR Standard Operating Procedure (STRONG STAR-ADM-001-5.0) for Review and Approval of Publications and Presentation and the International Committee of Medical Journal Editors (ICMJE) "Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals" updated January 2024.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Esketamine (Intranasal Spray) and Massed Prolonged Exposure (PE) in people with Post Traumatic Stress Disorder PTSD, run by The University of Texas Health Science Center at San Antonio 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 19 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: finished, as of the sponsor's last update on 28 Jan 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined 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.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Feasibility of Treatment using Esketamine and PE (time frame: Study start to closing to enrollment (approximately 12 months)). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06795659.

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 28 Jan 2026.

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