MDMA-Assisted CBCT for PTSD vs CBCT RCT

Study Overview
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Brief Summary
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This study aims to evaluate the safety, feasibility, acceptability, and effectiveness of MDMA-assisted Cognitive-Behavioral Conjoint Therapy (CBCT) versus CBCT alone for the treatment of Post-Traumatic Stress Disorder (PTSD). PTSD is a debilitating condition that significantly impacts interpersonal relationships and the functioning of individuals and their loved ones. There is also a well-established reciprocal relationship between interpersonal relationships, PTSD, and recovery. CBCT is a manualized treatment for PTSD that simultaneously addresses PTSD symptoms and relationship satisfaction. It provides dyads with behavioral tools to navigate PTSD-related challenges, as well as the knowledge behind PTSD and how it impacts relationships. Previous research has demonstrated the efficacy of CBCT in improving PTSD symptoms, partner functioning, and relationship satisfaction in both distressed and non-distressed dyads. MDMA is a drug commonly used recreationally that has been increasingly studied because of its ability to reduce the impact of PTSD symptoms. The effects of MDMA are reduced fear, enhanced communication, trust and introspection, and increased empathy and compassion. The effects of MDMA create a state that enhances the positive effects of therapy by increasing the ability to tolerate negative emotions and allowing clients to stay engaged in therapy without being overwhelmed by the intense emotions surrounding the memories of traumatic events. It is believed that MDMA may help promote the effects of CBCT due to its ability to induce empathy and interpersonal openness. This randomized study is the second study designed to explore the efficacy of combining MDMA-assisted therapy with CBCT. This study will enroll 30 dyads, where one individual has symptoms of PTSD. Participants will undergo a 7-week psychotherapy course, in MDMA-assisted CBCT or CBCT alone. In the MDMA-assisted CBCT, participants will go through CBCT sessions, and two doses of MDMA will be used as an adjunct to psychotherapy. Participants assigned to the CBCT-only condition will go through CBCT sessions and will have the opportunity to crossover and receive the two MDMA sessions after follow-up. The primary goal of this research is to contribute to the literature on MDMA-assisted CBCT by investigating its feasibility, safety, acceptability, and effectiveness, and by comparing it to active PTSD treatments.

Official Title
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A Randomized Trial of MDMA-Assisted Cognitive-Behavioural Conjoint Therapy (CBCT) Versus CBCT in Dyads in Which One Member Has Posttraumatic Stress Disorder (PTSD)

Conditions
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Post Traumatic Stress Disorder

Intervention / Treatment
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* Drug: MDMA assisted psychotherapy
* Behavioral: Psychotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Participant with PTSD Participant with PTSD Meet criteria for PTSD Have a close other person who is able and willing to participate in this study Are at least 18 years old Are a resident of Ontario and live within the Greater Toronto Area (GTA) Are in good physical health Are proficient in speaking and reading English Are willing to have all visits audio and video recorded Are able to swallow pills Agree to all study rules and commit to all medical and therapy visits If in psychotherapy, are willing to allow the study therapists to communicate directly with your therapist Are willing to stop taking psychiatric medications, herbal supplements, prescription and nonprescription medications during the study Agree to stay overnight on two separate occasions after each full-day MDMA-Assisted Therapy Session, and not to drive for at least 24 hours after taking MDMA Are not pregnant and will commit to not becoming pregnant during the study, if you are able to become pregnant Have a supportive relative, spouse, close friend or other caregiver not participating in this study who can serve as your emergency contact Agree to inform the researchers within 48 hours of any medical conditions and procedures Agree to not participate in any other clinical trials during this study Close Significant Other Have a close other person who meets criteria for PTSD and is able and willing to participate in this study Are at least 18 years old Are a resident of Ontario and live within the Greater Toronto Area (GTA) Are in good physical health Are proficient in speaking and reading English Are willing to have all visits audio and video recorded Are able to swallow pills Agree to all study rules and commit to all medical and therapy visits If in psychotherapy, are willing to allow the study therapists to communicate directly with your therapist Are willing to stop taking psychiatric medications, herbal supplements, prescription and nonprescription medications during the study Agree to stay overnight on two separate occasions after each full-day MDMA-Assisted Therapy Session, and not to drive for at least 24 hours after taking MDMA Are not pregnant and will commit to not becoming pregnant during the study, if you are able to become pregnant Have a supportive relative, spouse, close friend or other caregiver not participating in this study who can serve as your emergency contact Agree to inform the researchers within 48 hours of any medical conditions and procedure Agree to not participate in any other clinical trials during this study Exclusion Criteria Participant with PTSD Are pregnant or could become pregnant and not using birth control Have a history of, or a current psychotic disorder or bipolar 1 disorder or dissociative identity disorder Have a history of a medical condition that could make receiving MDMA unsafe (e.g. glaucoma, heart attack, stroke, aneurysm) Have a history of Diabetes Mellitus (Type 2) that a doctor determines is not stable Have hypothyroidism (low activity in the thyroid gland) and are not on thyroid replacement Have high blood pressure, a history of heart disease, heart failure, irregular activity in the heart or require heart medication Have liver disease with symptoms Have history of hyponatremia (when you have decreased levels of sodium in the blood, which can cause confusion, seizures, fatigue and low levels of consciousness) Have history of hyperthermia (when you have a dangerously overheated body, usually in response to hot, humid weather) Weigh less than 48 kg Have recently engaged in suicidal behaviour or had serious suicidal thoughts (this will be assessed by the study team) Require ongoing therapy with a psychiatric medication Have a current eating disorder with active purging Have current major depressive disorder with psychotic features Are a serious risk to others Have recently received Electroconvulsive Therapy (ECT) Have recently engaged in ketamine-assisted therapy or used ketamine Have current substance use disorder with physiological dependence (not including caffeine or nicotine) Have recently used Ecstasy (material represented as containing MDMA) Are not able to give adequate informed consent Are not able to adhere to the requirements for procedures, attendance and timing of visits, and observe limits regarding study staff time and support as indicated by a time-limited clinical trial Are currently engaged in compensation litigation whereby financial gain would be achieved from prolonged symptoms of PTSD or any other psychiatric disorders Close Significant Other Meet criteria for PTSD Are pregnant or could become pregnant and not using birth control Have a history of, or a current psychotic disorder or bipolar 1 disorder or dissociative identity disorder Have a history of a medical condition that could make receiving MDMA unsafe (e.g. glaucoma, heart attack, stroke, aneurysm) Have a history of Diabetes Mellitus (Type 2) that a doctor determines is not stable Have hypothyroidism (low activity in the thyroid gland) and are not on thyroid replacement Have high blood pressure, a history of heart disease, heart failure, irregular activity in the heart or require heart medication Have liver disease with symptoms Have history of hyponatremia (when you have decreased levels of sodium in the blood, which can cause confusion, seizures, fatigue and low levels of consciousness) Have history of hyperthermia (when you have a dangerously overheated body, usually in response to hot, humid weather) Weigh less than 48 kg Have recently engaged in suicidal behaviour or had serious suicidal thoughts (this will be assessed by the study team) Require ongoing therapy with a psychiatric medication Have a current eating disorder with active purging Have current major depressive disorder with psychotic features Are a serious risk to others Have recently received Electroconvulsive Therapy (ECT) Have recently engaged in ketamine-assisted therapy or used ketamine Have current substance use disorder with physiological dependence (not including caffeine or nicotine) Have recently used Ecstasy (material represented as containing MDMA) Are not able to give adequate informed consent Are not able to adhere to the requirements for procedures, attendance and timing of visits, and observe limits regarding study staff time and support as indicated by a time-limited clinical trial Are currently engaged in compensation litigation whereby financial gain would be achieved from prolonged symptoms of PTSD or any other psychiatric disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MDMA-Assisted CBCT Condition<br>Dyads will undergo a 7-week course of CBCT psychotherapy for PTSD with two sessions that integrate MDMA-assisted psychotherapy. MDMA will be administered in two separate sessions and integrated into the psychotherapy protocol. The two doses of MDMA during this study will be used as an adjunct to psychotherapy. | Drug: MDMA assisted psychotherapy<br>* This treatment combines MDMA with a well researched treatment for PTSD for dyads known as CBCT. Dyads will undergo a 7-week course of psychotherapy with two doses of MDMA will be used as an adjunct to psychotherapy.<br>* Other names: MDMA-assisted CBCT;|
| Active Comparator: CBCT-Only Condition<br>Dyads will undergo a 7-week course of CBCT psychotherapy for PTSD. Dyads who have undergone the CBCT-Only condition will have the option to do a crossover and have the two MDMA sessions after follow-up. | Behavioral: Psychotherapy<br>* A manualized treatment for PTSD for dyads wherein one person has symptoms of PTSD. This intervention is 7-week course of psychotherapy that is designed to simultaneously improve PTSD symptoms and relationship functioning through education and skill training.<br>* Other names: CBCT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Intervention Measure (FIM) | The Feasibility of Intervention Measure (FIM) is a self-report questionnaire in which respondents indicate the extent to which they believe that the treatment can be delivered in a given setting. Respondents indicate their responses on a five-point Likert-type (1=completely disagree, 5= completely agree). | 3-Month Follow-up | 
| Safety of Intervention | Safety will be assessed by examining the frequency and severity of adverse events (AEs), serious AEs (SAEs), treatment emergent AES (TEAEs), and AEs of special interest. Participants are asked to report any AEs, SAEs, TEAEs, and AEs of special interest as they happen and during any communication with the therapist or independent assessor. | Baseline (enrolment) to Follow-up (3-month follow-up) | 
| Intervention Appropriateness Measures (IAM) | Intervention Appropriateness Measures (IAM) is a self-report measure of the perceived fit, relevance, or compatibility of an intervention. Respondents record their answers on a five-point Likert-type scale (1=completely disagree, 5= completely agree). | 3-month follow-up | 
| Long Term Follow-Up Questionnaire (LTFUQ) | The Long Term Follow-Up Questionnaire (LTFUQ) is a self-report measure that assesses the long-term benefits and harms of MDMA-assisted therapy. | 3-Month Follow-up | 
| Clinician Administered PTSD Scale (CAPS-5) | The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. It contains symptom subscales, a total severity score, and a diagnostic score. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms. | Baseline (enrolment) to Follow-up (3-month follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Posttraumatic Stress Disorder Checklist for the DSM-5 (PCL-5) | PTSD Checklist for the DSM-5 (PCL-5) is a self-report questionnaire in which respondents indicate the presence and severity of PTSD symptoms, derived from the DSM-5 symptoms of PTSD. Participants indicate how much distress they have experienced due to symptoms on a five-point Likert-type scale (1 = not at all, 5 = extremely). The total PCL-5 score (a sum of all 20 items) provides an index of overall PTSD symptom severity with higher scores indicating higher severity. | Baseline (enrolment) to Follow-up (3-month follow-up) | 
| Quality of Relationships Inventory (QRI) | The Quality of Relationships Inventory (QRI) is a self-report questionnaire that uses the role of situational, intrapersonal, and interpersonal in social support processes to assess supportive and conflictual aspects of close non-intimate relationships. | Baseline (enrolment) to Follow-up (3-month follow-up) | 
| Couple Satisfaction Index (CSI) | The Couple Satisfaction Index (CSI) is a self-report questionnaire that measures intimate relationship functioning. Respondents answer most of the questions on a six-point Likert-type scale (0= never, 5= all the time) and one question on a seven-point Likert-type scale ( 0= extremely unhappy, 6= perfect). | Baseline (enrolment) to Follow-up (3-month follow-up) | 
| Patient Health Questionnaire-9 (PHQ-9) | The Patient Health Questionnaire-9 (PHQ-9) is used to assess depressive symptom severity. The PHQ-9 includes items which correspond with the diagnostic criteria for DSM-IV major depressive disorder. Scores can indicate either no depression, minimal, mild, moderate, moderately severe, or severe depression. Higher scores indicate higher severity in depressive symptoms. | Baseline (enrolment) to Follow-up (3-month follow-up) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDMA, Cognitive Behavioural Conjoint Therapy (CBCT), Relationship functioning