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

The University of Texas Health Science Center at San Antonio4 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Feasibility of Treatment using Esketamine and PE

Number of eligible referrals

Time frame: 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.

Time frame: Day 1 to 1 month

Enrollment proportion

Proportion of eligible participants

Time frame: Study start to closed to enrollment (approximately 12 months)

Adherence to treatment

Number of participants that adhered to and completed treatment

Time frame: 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.

Time frame: Day 1 to 1 month

CEQ for Esketamine (Credibility Score)

Time frame: 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.

Time frame: Day 1 to 1 month

CEQ for PE (Expectancy score)

Time frame: 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.