Comparing Standard vs. Modified Reconsolidation Blockade for the Treatment of Psychological Trauma: A Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Post-traumatic Checklist for the Diagnostic and Statistical Manual for Mental Disorders - 5th edition (PCL-5) scores
研究概览
简要总结
The investigators propose to examine a mismatch-based method of reconsolidation blockade for the treatment of psychological trauma in military personnel and Federal police officers. The standard reconsolidation blockade treatment (aka Reconsolidation Therapy) involves reactivating the trauma memory while under the influence of propranolol. The mismatch method of Reconsolidation Therapy will involve varying the contexts in which the weekly trauma memory retrieval will occur. This study will involve 10 visits (eligibility assessment, treatments, and follow-up visits) over a 6-month period for each participant. Treatments will be conducted once a week for a six-week period where the participant will take a dose of propranolol (or a placebo pill) 60 minutes prior to memory reactivation. The investigators hypothesize that reconsolidation blockade treatment will be as effective in treating PTSD among military personnel and Federal police officers, with the mismatch condition showing greater symptom improvement.
详细描述
Traumatic stress remains a treatment-refractory mental health problem characterized by symptoms of re-experiencing, avoidance, negative cognitions and affect, and hyperarousal. Due to the nature of their profession, military personnel and the Federal police officers (RCMP; Royal Canadian Mounted Police) are at a greater risk of suffering from traumatic stress. Thus, there is an important unmet need for developing novel treatments for trauma-related disorders, particularly for the military and RCMP.
Considering the pivotal role of negative emotional experiences in the development and persistence of PTSD, blocking the reconsolidation of such experiences opens the door to a novel and powerful treatment approach against this disorder. We (Brunet et al, 2018) have previously shown the efficacy of trauma memory reactivation performed under the influence of propranolol, a noradrenergic beta-receptor blocker, as a putative reconsolidation blocker, in reducing symptoms of post-traumatic stress disorder (PTSD). Although this therapeutic method was shown to be efficacious, it is hypothesized that symptomatic improvements may be increased by including a mismatch experience between what is expected during memory recall and the actual recall experience, in line with mismatch theory (Pedreira et al, 2004; see Ecker, 2015). In this study, we test the effects of a mismatch procedure by altering the context in which the trauma memory retrieval occurs. Standard and mismatch reconsolidation therapy procedures will be used to treat PTSD in military personnel and Federal police officers.
Primary objective:
• Compare the effects of Standard Reconsolidation Therapy using propranolol vs. placebo on PTSD symptoms one-week post-treatment.
Primary hypothesis:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
In this study, the investigators, therapists, outcomes assessors, and research participants will be blind to study medication allocation.
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
- •(i) Male or female 18-65 years old;
- •(ii) Individuals who are either:
- •Employed full-time as part of the Canadian or US military forces or the RCMP;
- •On leave of absence from Canadian or US military forces, or the RCMP;
- •Veterans of the Canadian or US military forces or the RCMP;
- •(iii) Evidence of a personally signed and dated informed consent form;
- •(iv) Individuals suffering from occupationally related PTSD, as defined by the DSM-5, for 6 consecutive months or more.
- •(v) Females of childbearing potential willing to use contraception for the duration of the treatment period of the study.
排除标准
- •(i) Basal systolic blood pressure < 100 mm Hg;
- •(ii) Basal heart rate < 50 BPM;
- •(iii) Medical conditions contraindicating the administration of propranolol or beta blockers
- •(iv) A known hypersensitivity to propranolol or any of the study product or placebo ingredients;
- •(v) Clinically significant lactose intolerance;
- •(vi) Use of medication that involves unwanted interactions with propranolol including but not limited to other beta-blockers, anti-arrhythmic medications, and calcium channel blockers;
- •(vii) Current use of propranolol;
- •(viii) Pregnant or breast-feeding women;
- •(ix) Individuals with borderline personality, bipolar disorder, psychosis;
- •(x) Current DSM-5 substance dependence;
- •(xi) Active suicidal ideations, as demonstrated by a response of 2 or 3 on item 7 of the Beck Depression Inventory - Short Form;
- •(xii) A score below 'moderately ill' on the severity scale of the Clinical Global Impression scale;
- •(xiii) Participating in active litigation related to the traumatic event (Veterans Affairs Canada claims are permitted, excluding judicial claims);
- •(xiv) Strong dissociative tendencies, as evidenced by the Dissociative Experience Scale (8-item version, DES-T);
- •(xv) Suspected or confirmed traumatic brain injury during the last 24 months;
- •(xvi) Understanding neither English nor French;
- •(xvii) Participants who receive exposure-based cognitive-behavioral therapy during the treatment phase of the study;
- •(xviii) Presence of any medical condition that in the opinion of the investigator may compromise patient safety or study objectives.
研究组 & 干预措施
Propranolol and standard trauma memory reactivation group
Oral propranolol will be administered 60 minutes prior to writing (Treatment 1) or reading aloud a trauma narrative.
干预措施: Propranolol (Drug)
Placebo and standard trauma memory reactivation group
Oral placebo will be administered 60 minutes prior to writing (Treatment 1) or reading aloud a trauma narrative.
干预措施: Placebo (Drug)
Propranolol and mismatch trauma memory reactivation group
Oral propranolol will be administered 60 minutes prior to a memory reactivation procedure involving variations in the contexts where the trauma memory reactivations occur.
干预措施: Propranolol (Drug)
Placebo and mismatch trauma memory reactivation group
Oral placebo will be administered 60 minutes prior to a memory reactivation procedure involving variations in the contexts where the trauma memory reactivations occur.
干预措施: Placebo (Drug)
结局指标
主要结局
Post-traumatic Checklist for the Diagnostic and Statistical Manual for Mental Disorders - 5th edition (PCL-5) scores
时间窗: Questionnaire administered at weeks 0 and 7
Change from baseline (week 0) to week 7 in PCL-5 scores
次要结局
- Beck Depression Inventory (BDI) scores(Questionnaire administered at weeks 0, 1, 2, 3, 4 , 5, 6, 7, 13 and 26)
- Clinical Global Impression-Improvement (CGI-I) scores(Questionnaire administered at weeks 0, 7 and 26)
- World Health Organization - Quality of Life BREF(Questionnaire administered at weeks 0, 7, and 26)
- Post-traumatic Checklist for the Diagnostic and Statistical Manual for Mental Disorders - 5th edition (PCL-5) scores(Questionnaire administered at weeks 0, 1, 2, 3, 4, 5, 6, 13 and 26)
- Social Functioning Questionnaire (QFS)(Questionnaire administered at weeks 0, 7, and 26)
- Mini Psychiatric Interview, version 7 (MINI-7)(Questionnaire administered at weeks 0, 7 and 26)
- Dissociative Experiences Scale (DES-T)(Questionnaire administered at week 0.)
- International Trauma Questionnaire (ITQ)(Questionnaire administered at baseline and weeks 0, 7, and 26)
研究者
Alain Brunet, Ph.D.
Primary Investigator and Full Professor, Department of Psychiatry, McGill University.
Douglas Mental Health University Institute