An Open-Label, Multicenter, Randomized, Non-Inferiority Study to Evaluate the Safety and Effectiveness of Group vs. Individual MDMA-Assisted Therapy in PTSD Patients Diagnosed Following the Events of October 7, 2023
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 168
- 试验地点
- 2
- 主要终点
- Change in PTSD symptoms as measured by CAPS-5
研究概览
简要总结
The goal of this clinical trial is to evaluate the safety, tolerability and effectiveness of group-based MDMA-assisted therapy compared to individual MDMA-assisted therapy in participants with PTSD, who were diagnosed following the events of 7 October 2023. The main questions it aims to answer are: safety and tolerability? effectiveness? Researchers will compare group-based MDMA-assisted therapy to individual MDMA-assisted therapy to see if group-based MDMA-assisted therapy is not inferior to individual MDMA-assisted therapy, in terms of safety and effectiveness.
Participants will be randomized to one of two study arms: group-based MDMA-assisted therapy or individual MDMA-assisted therapy receive MDMA HCl administered orally in a divided dose. Participate in preparatory sessions, MDMA dosing sessions, and integration sessions. Be monitored for adverse events and suicidality (C-SSRS). Be monitored by an external Data Safety Monitoring Board (DSMB).
详细描述
PTSD (post-traumatic stress disorder) is a severe and debilitating disorder that may occur following a traumatic event, with significant consequences on daily life, such as inability to form beneficial relationships, inability to maintain employment, reduced cognitive and psycho-social functioning, depression, anxiety and alcohol disorders and use of addictive substances. Available PTSD treatments include medications and therapy, but they effectively treat only a small portion of people, indicating a need to develop treatments targeting durable remission of PTSD.
MDMA is a phenylisopropylamine derivative. MDMA increases levels of serotonin and also increases levels of oxytocin and vasopressin, which are associated with increased trust and reduced reactivity to threatening situations. MDMA is not used as a treatment by itself, but as an adjunct that enhances the effectiveness of psychotherapy.
Participants will complete pre-screening. Screening and enrollment procedures include review of medical and psychiatric history, documentation of prior/current medications, and completion of questionnaires. Participants will be asked to complete questionnaires throughout the study, including during screening and at multiple time points across study visits, to assess symptoms and other study-related measures. Eligible participants will be randomized, with allocation managed centrally, to one of two treatment arms.
Prior to administration of the investigational product, participants will attend preparatory sessions. MDMA HCl will be administered orally in a divided dose, with a supplemental dose administered 1.5 to 2 hours after the initial dose. During dosing sessions, participants will be monitored, including measurement of vital signs by trained medical staff. Safety procedures include physical examination, urine drug testing, ECG assessment, and safety laboratory tests as specified in the protocol.
Safety monitoring will include assessment of adverse events and C-SSRS. Study safety will be overseen by an external Data Safety Monitoring Board (DSMB).
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
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Are at least 18 years old.
- •At Screening, meet DSM-5 criteria for current PTSD that has been diagnosed past 7/10/23 and the events following.
- •At Screening, have at least moderate PTSD symptoms in the last month, based on PCL-5 total score of 36 or greater, conducted by certified Study coordinators.
- •Are fluent in speaking and reading the predominantly used or recognized language of the study site (Hebrew).
- •Are able to swallow pills.
- •Participant where in psychotherapy prior to the study. If the participant is still in psychotherapy during study enrollment, they consent to continue therapy during the study and provide consent for the investigator to communicate with the therapist as needed.
- •Must provide a contact (relative, spouse, close friend, or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.
- •Must agree to inform the investigators within 48 hours of any medical conditions and procedures.
- •Agree to the following lifestyle modifications (see lifestyle modifications section) : comply with requirements for fasting and refraining from certain medications prior to Experimental Sessions, not participate in any other interventional clinical trials during the duration of the study, remain overnight at the study site after each Experimental Session and be driven home after, and commit to medication dosing, therapy, and study procedures.
- •If able to become pregnant (i.e. assigned female at birth, fertile, following menarche and until becoming post-menopausal unless permanently sterile), must have a highly sensitive negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 10 days after the last Experimental Session. Adequate birth control methods include intrauterine device (IUD), injected, implanted, intravaginal, or transdermal hormonal methods, abstinence, oral hormones plus a barrier contraception, vasectomized sole partner, or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones (i.e. condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom).
- •Holds a permanent address in the next 6 months.
- •Medical History
- •May have well-controlled hypertension that has been successfully treated with anti-hypertensive medicines, if they pass additional screening to rule out underlying cardiovascular disease.
- •May have asymptomatic Hepatitis C virus (HCV) that has previously undergone evaluation and treatment as needed.
- •May have alcohol or substance use disorder if the participant is not in withdrawal or requiring detox. Participants must have a plan, agreed upon by the investigator, therapy team, and study physician, to reduce use of alcohol or other substances and to manage symptoms without self-medicating. Enrollment will require that, in the judgment of the investigator, therapy team, and study physician, the plan for decreasing substance use is realistic and has a good chance of succeeding in order to prevent substance use from impacting the safety or efficacy of the investigational treatment.
- •May have a history of or current Diabetes Mellitus (Type 2) if additional screening measures rule out underlying cardiovascular disease, if the condition is judged to be stable on effective management, and with approval by the study physician.
- •May have hypothyroidism if taking adequate and stable thyroid replacement medication.
- •May have a history of, or current, glaucoma if approval for study participation is received from an ophthalmologist.
排除标准
- •Are not able to give adequate informed consent.
- •Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or study clinician, contraindicates participation in the study.
- •Active military duty expected in the following 12 months.
- •Death of a close person in the past 6 months.
- •Psychiatric History
- •Have received Electroconvulsive Therapy, Transcranial Magnetic Stimulation, or Ketamine Therapy within 12 weeks of enrollment.
- •Have a history of, or a current diagnosis of schizophrenia, schizoaffective disorder, major depressive disorder with psychotic features, psychotic disorder, bipolar disorder I or II (with or without psychotic features), or dissociative identity disorder assessed by medical history, investigator interview and the Mini-International Neuropsychiatric Interview (MINI).
- •Have a current substance use disorder other than caffeine or nicotine that the investigators, therapy team, and/or study physician judge to be a safety concern for enrollment in the study or that could interfere with the therapeutic process or with other aspects of study participation as assessed by clinical interview per DSM-5 as well as Audit and Dudit questionnaires. Any participant who is not able to agree or adhere to a plan to reduce use and manage symptoms will not be enrolled.
- •Have an active illicit (other than cannabis) or prescription drug substance use disorder at any severity within 12 months prior to enrollment.
- •Have current Personality Disorders Cluster A (paranoid, schizoid, schizotypal), Cluster B (antisocial, borderline, histrionic, narcissistic), or Cluster C (avoidant, dependent, obsessive-compulsive) assessed via SCID-5-PD.
- •Any participant presenting current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS, and clinical judgment of the investigator will be excluded; however, history of suicide attempts is not an exclusion. Any participant who is likely to require hospitalization related to suicidal ideation and behavior, in the judgment of the investigator, will not be enrolled. Any participant presenting with the following on the Baseline C-SSRS will be excluded:
- •Suicidal ideation score of 4 or greater within the last 6 months of the assessment at a frequency of once a week or more.
- •Suicidal ideation score of 5 within the last 6 months of the assessment.
- •Any suicidal behavior, including suicide attempts or preparatory acts, within the last 6 months of the assessment. Participants with non-suicidal self-injurious behavior may be included if approved by the study physician.
- •Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist.
- •Have a blood or needle phobia that interferes with obtaining necessary blood work.
- •Have an immediate family member diagnosed with a psychotic disorder to the participant's knowledge.
- •Medical History
- •Have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of increases in blood pressure and heart rate. This includes, but is not limited to, a history of myocardial infarction, cerebrovascular accident, or aneurysm. Participants with other mild, stable chronic medical problems may be enrolled if the study physician and sponsor-investigator agree the condition would not significantly increase the risk of MDMA administration or be likely to produce significant symptoms during the study that could interfere with study participation or be confused with side effects of the use of MDMA. Examples of stable medical conditions that could be allowed include, but are not limited to Diabetes Mellitus (Type 2), Human Immunodeficiency Virus (HIV) infection, Gastroesophageal Reflux Disease (GERD), etc. Any medical disorder judged by the investigator to significantly increase the risk of MDMA administration by any mechanism would require exclusion.
- •Have uncontrolled essential hypertension using the standard criteria of the American Heart Association (values of 140/90 milligrams of Mercury [mmHg] or higher assessed on three separate occasions).
- •Have a history of ventricular arrhythmia at any time, other than premature ventricular contractions (PVCs) in the absence of ischemic heart disease.
- •Have Wolff-Parkinson-White syndrome or any other accessory pathway that has not been successfully eliminated by ablation.
- •Have a history of arrhythmia, other than premature atrial contractions (PACs) or occasional PVCs in the absence of ischemic heart disease, within 12 months of screening. Participants with a history of atrial fibrillation, atrial tachycardia, atrial flutter or paroxysmal supraventricular tachycardia or any other arrhythmia associated with a bypass tract may be enrolled only if they have been successfully treated with ablation and have not had recurrent arrhythmia for at least one year off all antiarrhythmic drugs and confirmed by a cardiologist.
- •Have a marked Baseline prolongation of QT/QTc interval e.g., repeated demonstration of a QTc interval > 450 milliseconds (ms) in males and >460 ms in females corrected using Fridericia's formula. For transgender or non-binary participants, QTc interval will be evaluated based on sex assigned at birth, unless the participant has been on hormonal treatment for 5 or more years.
- •Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
- •Require use of concomitant medications that prolong the QT/QTc interval during Experimental Sessions. Refer to protocol section on Concomitant Medications.
- •Have symptomatic liver disease or have significant liver enzyme elevations.
- •Have history of hyponatremia or hyperthermia.
- •Weigh less than 48 kilograms (kg).
- •Have engaged in ketamine-assisted therapy or used ketamine within 12 weeks of enrollment.
研究组 & 干预措施
Individual MDMA-assisted therapy
Participants will receive individual MDMA-assisted therapy. MDMA HCl will be administered orally during dosing sessions in a divided dose, with a supplemental dose administered 1.5 to 2 hours after the initial dose. Participants will attend preparatory sessions and integration sessions according to the protocol.
干预措施: MDMA HCl (Drug)
Group-based MDMA-assisted therapy
Participants will receive group-based MDMA-assisted therapy (up to 7 participants per group). Each group will include participants with the same type of trauma. MDMA HCl will be administered orally during dosing sessions in a divided dose, with a supplemental dose administered 1.5 to 2 hours after the initial dose. Participants will attend preparatory sessions and integration sessions according to the protocol.
干预措施: MDMA HCl (Drug)
结局指标
主要结局
Change in PTSD symptoms as measured by CAPS-5
时间窗: Baseline to end-of-treatment visit (Week 17 in the GMAT; Week 13 in the IMAT)
Change from baseline in PTSD symptoms as measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5).
Change in PTSD symptoms as measured by PCL-5
时间窗: Baseline to end-of-treatment visit (Week 17 in the GMAT; Week 13 in the IMAT)
Change from baseline in PTSD symptoms as measured by the PTSD Checklist for DSM-5 (PCL-5).
次要结局
- Safety and tolerability(From baseline through end-of-study visit (Week 17 in the GMAT; Week 13 in the IMAT))
- Suicidal ideation and behavior assessed with C-SSRS(From baseline through end-of-study visit Week 17 in the GMAT; Week 13 in the IMAT), assessed throughout the treatment period)
- Change in systolic and diastolic blood pressure(From pre-IP administration to end of each Experimental Session (Weeks 6, 10, and 14 in the GMAT arm; Weeks 4, 7, and 10 in the IMAT arm))
- Change in heart rate(From pre-IP administration to end of each Experimental Session (Weeks 6, 10, and 14 in the GMAT arm; Weeks 4, 7, and 10 in the IMAT arm))
- Change in respiratory rate(From pre-IP administration to end of each Experimental Session (Weeks 6, 10, and 14 in the GMAT arm; Weeks 4, 7, and 10 in the IMAT arm))
- Change in body temperature(From pre-IP administration to end of each Experimental Session (Weeks 6, 10, and 14 in the GMAT arm; Weeks 4, 7, and 10 in the IMAT arm))