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

NCT06795659 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00001076
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Post Traumatic Stress Disorder PTSD

Keywords

Massed Prolonged Exposure; Esketamine

Outcome Measures

Primary Outcomes (10)

• Feasibility of Treatment using Esketamine and PE

  Number of eligible referrals

  Study start to closing to enrollment (approximately 12 months)

• 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.

  Day 1 to 1 month

• Enrollment proportion

  Proportion of eligible participants

  Study start to closed to enrollment (approximately 12 months)

• Adherence to treatment

  Number of participants that adhered to and completed treatment

  Study start to closed to enrollment (approximately 12 months)

• 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.

  Day 1 to 1 month

• 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.

  Day 1 to 1 month

• 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.

  Day 1 to 1 month

• 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.

  Day 1 to 1 month

• 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.

  Baseline to 1 month

• 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.

  Baseline to 1 month

Secondary Outcomes (5)

• Depressive Symptom Index - Suicidality Subscale (DSI-SS)

  Baseline to 1 month

• Generalized Anxiety Disorder Screener

  Baseline to 1 month

• Patient Health Questionnaire-9

  Baseline to 1 month

• Posttraumatic Cognitions Inventory (PTCI)

  Baseline to 1 month

• Brief Inventory of Psychosocial Functioning

  Baseline to 1 month

Study Arms (1)

Esketamine combined with Prolonged Exposure for PTSD

EXPERIMENTAL

Esketamine (intranasal ketamine) will be administered 6 times over a 2-week period after administering PE sessions

Drug: Esketamine (Intranasal Spray); Behavioral: Massed Prolonged Exposure (PE)

Interventions

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).

Esketamine combined with Prolonged Exposure for PTSD

Massed Prolonged Exposure (PE) BEHAVIORAL

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)

Esketamine combined with Prolonged Exposure for PTSD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Institute for Integration of Medicine & Science-UT Health San Antonio: collaborator
• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Combat Disorders

Interventions

Esketamine

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Study Officials

• Casey Straud, PsyD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Open-label, proof-of-concept, pilot trial

Study Record Dates

• First Submitted: January 21, 2025
• First Posted: January 28, 2025
• Study Start: June 9, 2025
• Primary Completion: January 16, 2026
• Study Completion: January 16, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: At study completion when data are published in a peer review journal.
• Access Criteria: At study completion, data will be published in a peer review journal. Any information that is not presented in the publication may be requested through the corresponding author or the STRONG STAR Consortium Repository

Locations

US (1)