Effects of THC on Retention of Memory for Fear Extinction Learning in PTSD: R33 Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 102
- 试验地点
- 1
- 主要终点
- Subjective Units of Distress Scale (SUDS)
研究概览
简要总结
The goal of this study is to look at how a type of drug called cannabinoids are related to the processing of fear signals, the experience of emotions and fear, and the pattern of activity in the brain that is involved in these processes and how this relates to the treatment of post-traumatic stress disorder (PTSD). PTSD is an anxiety disorder that occurs after experiencing a traumatic event(s) and is characterized by unwanted memories of the trauma(s) through flashbacks or nightmares, avoidance of situations that remind the person of the event, difficulty experiencing emotions, loss of interest in activities the person used to enjoy, and increased arousal, such as difficulty falling asleep or staying asleep, anger and hypervigilance. The information gained from this study could lead to the development of new treatments for persons who suffer from anxiety or fear-based disorders.
详细描述
The total time commitment estimated per participant 18 study visits. This is broken down below:
Visit 1: Questionnaires, Screening, and Orientation: During this visit the potential participant will learn about the study procedures, sign the informed consent documents, and fill out a packet of forms that ask about his or her race and ethnic background, use of drugs and alcohol and physical and mental health.
Visit 2: Pre-Treatment Behavioral Tests and and Magnetic Resonance (MR) Scan: During this visit the participant will complete several computer tasks, and the study staff will be measuring reaction time and psychophysiological measures.The tasks that the participant will perform will show three different images and an aversive stimulus (e.g. loud burst of noise or animated snake) may follow one image most of the time, while the other images may never be followed by the aversive cue. The participant will need to try to predict whether the aversive cue will occur or not based on which image is shown and will be asked to repeatedly rate on a scale how likely it is that he or she thinks an aversive cue will occur after each image. Lastly, during the session the participant will also be asked to report his or her level of anxiety on a scale from 0 to 100.
Visit 3: Pre-Treatment Behavioral Tests and MR Scan: This visit will be very similar to Visit 2. Participants will participate in the same type of task inside the MR scanner, while the study staff measures reaction time and psychophysiological responding and brain activation. Participants will view the same images he or she did previously, and may experience the same aversive stimulus as during Visit 2. Participants will again be asked to rate how much they expect to experience the aversive stimulus after each image and will also be asked to report their level of anxiety on a scale from 0 to 100.
Visits 4 & 5: Prolonged Exposure (PE) Sessions 1 & 2: These sessions will consist of psychoeducation that includes discussion or reactions to trauma , treatment rationale, breathing retraining, and review of SUDS to assess level of distress from 0 to 100 (100=extreme anxiety/distress) when facing fears. One session occurs weekly across 2 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Between ages 18-60
- •Willing and able to consent to study
- •Generally medically and neurologically healthy (including no evidence of intellectual disability or serious cognitive impairment that would interfere with task performance)
- •Exposure to Criterion A stressor defined by CAPS-5 and identified by Life Events Checklist-5 (LEC-5)
- •Significant PTSD severity as indicated by CAPS-5 diagnosis and/or score >= 25 of at least one month prior to study entry, PTSD is patient's primary concern
排除标准
- •Positive urine pregnancy test prior to fMRI, self-reported current pregnancy during screening, or planning pregnancy
- •Currently breastfeeding/ lactating
- •MRI contraindications (e.g., ferrous metal in head/body)
- •Pervasive development disorder history
- •Traumatic brain injury (TBI) with current cognitive impairment related to TBI
- •Risk of harm to self or others that requires immediate intervention
- •Presence of contraindications, current or past allergic or adverse reaction, or known sensitivity to cannabinoid-like substances (dronabinol/marijuana/cannabis/THC, cannabinoid oil, sesame oil, gelatin, glycerin, and titanium dioxide)
- •Lack of fluency in English
- •Inability to tolerate small, enclosed spaces without anxiety (e.g. claustrophobia
- •Exclusively left-handed (score of -100 on Handedness Questionnaire)
- •Current or past diagnosis of bipolar, schizophrenia spectrum, psychotic and related disorders
- •Current severe alcohol or substance use
- •Comorbid mood or anxiety disorder that is primary to PTSD
- •Concomitant treatment with medication taken daily that has level 1 evidence indicating severe drug-drug interactions with dronabinol
研究组 & 干预措施
Placebo capsule
In a randomized, double-blind, placebo-controlled, between-subjects design, the investigators will administer a single oral dose of dronabinol (7.5mg) or placebo (PBO) approximately two hours prior to each weekly exposure session (up to 9 sessions) in a standard prolonged exposure treatment protocol comprising 12 session overall.
Half of the participants will receive 7.5mg dronabinol (n=50) and the other half of the participants will receive placebo (n=50).
干预措施: Placebo capsule (Drug)
Dronabinol 7.5 milligram oral capsule
In a randomized, double-blind, placebo-controlled, between-subjects design, the investigators will administer a single oral dose of dronabinol (7.5mg) or placebo (PBO) approximately two hours prior to each weekly exposure session (up to 9 sessions) in a standard prolonged exposure treatment protocol comprising 12 session overall.
Half of the participants will receive 7.5mg dronabinol (n=50) and the other half of the participants will receive placebo (n=50).
干预措施: Dronabinol 7.5 milligram oral capsule (Drug)
结局指标
主要结局
Subjective Units of Distress Scale (SUDS)
时间窗: Through study completion, an average of 3 months.
To assess the change in level of distress from 0 to 100 when facing fears. The higher the number on the scale the more severe the level of distress experienced.
Psychophysiology
时间窗: Through study completion, an average of 3 months.
Skin conductance response (SCR): change in SCR \[peak amplitude from 0.5-4.5 sec following stimulus presentation minus average 2 second baseline prior to stimulus presentation\].
PTSD Checklist (PCL-5)
时间窗: Through study completion, an average of 3 months.
To track PTSD symptom change for each participant. The PCL-5 is a 20-item questionnaire. The self-report rating scale is 0-4 for each symptom: "Not at all," "A little bit," Moderately," "Quite a bit," and "Extremely", respectively. A total symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items.
Brain Measures
时间窗: Through study completion, an average of 3 months.
functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) percent signal change within region of interests \[amygdala; ventromedial prefrontal cortex; hippocampus\]
Clinician Administered PTSD Scale for Diagnostic and Statistical Manual (DSM)-5 (CAPS-5)
时间窗: Through study completion, an average of 3 months.
To track PTSD symptom change for each participant. The CAPS is the gold standard in PTSD assessment. The CAPS is a 30-item structured interview. In addition to assessing the 20 DSM-5 PTSD symptoms, questions target the onset and duration of symptoms, subjective distress, impact of symptoms on social and occupational functioning, improvement in symptoms since a previous CAPS administration, overall response validity, overall PTSD severity, and specifications for the dissociative subtype. The assessor combines information about frequency and intensity of an item into a single severity rating. Total symptom severity score is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms. The five-point CAPS-5 symptom severity rating scale is used for all symptoms (0, Absent; 1, mild; 2, Moderate/threshold; 3, Severe/markedly elevated; 4, Extreme/incapacitating). Total CAPS-5 symptom severity scores range from 0-80, with higher scores indicating worse PTSD symptom severity.
Expectancy Ratings
时间窗: Through study completion, an average of 3 months.
To assess the change in expected likelihood that an aversive cue (e.g. noise burst or shock) will occur or not based on while slide was shown, participants will repeatedly rate their expectancy of the aversive cue using a button box on a scale from 1 to 3 \[1 = certain that the aversive cue will be presented; 2 = certain that the aversive cue will not be presented; 3 = uncertain whether the aversive cue will be presented\].
次要结局
- End of Session Questionnaire (ESQ)(Through study completion, an average of 3 months.)
- Heart Rate(Through study completion, an average of 3 months.)
- Visual Analogue Scale of Mood (VAS)(Through study completion, an average of 3 months.)
- Drug Effects Questionnaire (DEQ)(Through study completion, an average of 3 months.)
- State-Trait Anxiety Inventory (STAI)(Through study completion, an average of 3 months.)
- Addiction Research Center Inventory (ARCI)(Through study completion, an average of 3 months.)
- Blood Pressure(Through study completion, an average of 3 months.)
研究者
Christine Rabinak, PhD
Associate Professor & Principal Investigator
Wayne State University