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

Phase 1

Not yet recruiting

• Conditions: Post Traumatic Stress Disorder PTSD
• Interventions: Drug: Esketamine (Intranasal Spray); Behavioral: Massed Prolonged Exposure (PE)

• Registration Number: NCT06795659
• Lead Sponsor: The University of Texas Health Science Center at San Antonio

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.

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.

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-21
• Study First Submitted QC: 2025-01-21
• Last Update Submitted: 2025-01-21
• Study First Posted: 2025-01-28
• Last Update Posted: 2025-01-28
• Study Start: 2025-02-20
• Primary Completion: 2025-12-30
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

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

Exclusion Criteria

1. Young adults (18-24) currently taking any antidepressant.
2. Current manic episode or psychotic symptoms requiring immediate stabilization or hospitalization.
3. Moderate or greater severity for alcohol or substance use disorder (DSM-5) in the previous six months.
4. A history of ketamine or phencyclidine abuse.
5. Evidence of a traumatic brain injury severe enough to interfere with comprehension and responding to the baseline screening questionnaires.
6. 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)
7. Other psychiatric disorders severe enough to warrant designation as the primary disorder as determined by clinician judgment.
8. Current use (with past 4 weeks) of any prohibited concomitant medications.
9. 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 during the time of the study (i.e., for pain control).
10. Uncontrolled hypertension or tachycardia.
11. A history of sensitivity or adverse reaction to ketamine or its excipients.
12. An unstable medical, cardiovascular, pulmonary, or neurological condition that the investigator considers a contraindication to ketamine administration
13. Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation.
14. Intracerebral hemorrhage.
15. Pregnancy or breastfeeding; women of childbearing potential unwilling to utilize reliable methods of contraception
16. History of nasal surgery or nasal obstructions experienced as an adult.
17. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Esketamine combined with Prolonged Exposure for PTSD	Esketamine (Intranasal Spray)	Esketamine (intranasal ketamine) will be administered 6 times over a 2-week period after administering PE sessions
Esketamine combined with Prolonged Exposure for PTSD	Massed Prolonged Exposure (PE)	Esketamine (intranasal ketamine) will be administered 6 times over a 2-week period after administering PE sessions

Primary Outcome Measures

Name	Time	Method
Feasibility of Treatment using Esketamine and PE	Study start to closing to enrollment (approximately 12 months)	Number of eligible referrals
Satisfaction with Therapy and Therapist Scale - Revised (STTS-R)	Day 1 to 1 month	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.
Enrollment proportion	Study start to closed to enrollment (approximately 12 months)	Proportion of eligible participants
Adherence to treatment	Study start to closed to enrollment (approximately 12 months)	Number of participants that adhered to and completed treatment
The Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (CAPS-5)	Baseline to 1 month	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.
CEQ for Esketamine (Expectancy Score)	Day 1 to 1 month	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.
CEQ for PE (Credibility score)	Day 1 to 1 month	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.
CEQ for Esketamine (Credibility Score)	Day 1 to 1 month	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.
CEQ for PE (Expectancy score)	Day 1 to 1 month	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.
Post Traumatic Stress Disorder (PTSD) (PCL-5) Checklist-5 Change in Score	Baseline to 1 month	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.

Secondary Outcome Measures

Name	Time	Method
Depressive Symptom Index - Suicidality Subscale (DSI-SS)	Baseline to 1 month	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.
Brief Inventory of Psychosocial Functioning	Baseline to 1 month	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.
Generalized Anxiety Disorder Screener	Baseline to 1 month	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).
Patient Health Questionnaire-9	Baseline to 1 month	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).
Posttraumatic Cognitions Inventory (PTCI)	Baseline to 1 month	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)

Trial Locations

Locations (1)

The University of Texas Health Science Center at San Antonio; 🇺🇸 San Antonio, Texas, United States