Combining Esketamine and Prolonged Exposure for PTSD: A Proof-of-Concept Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Feasibility of Treatment using Esketamine and PE
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
- •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.
研究组 & 干预措施
Esketamine combined with Prolonged Exposure for PTSD
Esketamine (intranasal ketamine) will be administered 6 times over a 2-week period after administering PE sessions
干预措施: Esketamine (Intranasal Spray) (Drug)
Esketamine combined with Prolonged Exposure for PTSD
Esketamine (intranasal ketamine) will be administered 6 times over a 2-week period after administering PE sessions
干预措施: Massed Prolonged Exposure (PE) (Behavioral)
结局指标
主要结局
Feasibility of Treatment using Esketamine and PE
时间窗: Study start to closing to enrollment (approximately 12 months)
Number of eligible referrals
Satisfaction with Therapy and Therapist Scale - Revised (STTS-R)
时间窗: 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
时间窗: Study start to closed to enrollment (approximately 12 months)
Proportion of eligible participants
Adherence to treatment
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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.
次要结局
- Depressive Symptom Index - Suicidality Subscale (DSI-SS)(Baseline to 1 month)
- Brief Inventory of Psychosocial Functioning(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)
研究者
Casey Straud
Associate Professor
The University of Texas Health Science Center at San Antonio