Clinical trial NCT06795659: Combining Esketamine and Prolonged Exposure Treatment for PTSD (Post Traumatic Stress Disorder)
Official title: Combining Esketamine and Prolonged Exposure for PTSD: A Proof-of-Concept Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Post Traumatic Stress Disorder PTSD
Keywords: Massed Prolonged Exposure
Esketamine
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: Institute for Integration of Medicine & Science-UT Health San Antonio
First posted: 2025-01-28
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, proof-of-concept, pilot trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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. Lifetime history of psychotic disorder or history of significant psychotic symptoms.
3. Lifetime history of manic episode.
4. Moderate or greater severity for alcohol or substance use disorder (DSM-5) in the previous six months.
5. A history of ketamine or phencyclidine abuse.
6. Evidence of a traumatic brain injury severe enough to interfere with comprehension and responding to the baseline screening questionnaires.
7. 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)
8. Other psychiatric disorders severe enough to warrant designation as the primary disorder as determined by clinician judgment.
9. Current use (with past 4 weeks) of any prohibited concomitant medications
10. Benzodiazepines, other medications, sedatives, acute alcohol use, or recreational drug use that would put patients at risk in the judgment of clinical providers).
11. Planned use of ketamine (i.e., for pain control) or participation in another trauma-focused psychotherapy during the time of the study.
12. Uncontrolled hypertension or tachycardia
13. A history of sensitivity or adverse reaction to ketamine or its excipients
14. An unstable medical, cardiovascular, pulmonary, or neurological condition that the investigator considers a contraindication to ketamine administration
15. Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation.
16. Intracerebral hemorrhage.
17. Pregnancy or breastfeeding; women of childbearing potential unwilling to utilize reliable methods of contraception
18. History of nasal surgery or nasal obstructions experienced as an adult.
19. 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.

Primary outcomes:
measure: Feasibility of Treatment using Esketamine and PE
timeFrame: Study start to closing to enrollment (approximately 12 months)
measure: Satisfaction with Therapy and Therapist Scale - Revised (STTS-R)
timeFrame: Day 1 to 1 month
measure: Enrollment proportion
timeFrame: Study start to closed to enrollment (approximately 12 months)
measure: Adherence to treatment
timeFrame: Study start to closed to enrollment (approximately 12 months)
measure: CEQ for Esketamine (Expectancy Score)
timeFrame: Day 1 to 1 month
measure: CEQ for Esketamine (Credibility Score)
timeFrame: Day 1 to 1 month
measure: CEQ for PE (Credibility score)
timeFrame: Day 1 to 1 month
measure: CEQ for PE (Expectancy score)
timeFrame: Day 1 to 1 month
measure: Post Traumatic Stress Disorder (PTSD) (PCL-5) Checklist-5 Change in Score
timeFrame: Baseline to 1 month
measure: The Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (CAPS-5)
timeFrame: Baseline to 1 month
Secondary outcomes:
measure: Depressive Symptom Index - Suicidality Subscale (DSI-SS)
timeFrame: Baseline to 1 month
measure: Generalized Anxiety Disorder Screener
timeFrame: Baseline to 1 month
measure: Patient Health Questionnaire-9
timeFrame: Baseline to 1 month
measure: Posttraumatic Cognitions Inventory (PTCI)
timeFrame: Baseline to 1 month
measure: Brief Inventory of Psychosocial Functioning
timeFrame: Baseline to 1 month
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Casey Straud, PsyD
role: PRINCIPAL_INVESTIGATOR
References: