Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effects of MDMA on Prefrontal and Amygdala Activation in PTSD.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03752918
Recruitment Status : Recruiting
First Posted : November 26, 2018
Last Update Posted : September 11, 2020
Sponsor:
Information provided by (Responsible Party):
Benjamin Kelmendi, MD, Yale University

Tracking Information
First Submitted Date  ICMJE November 16, 2018
First Posted Date  ICMJE November 26, 2018
Last Update Posted Date September 11, 2020
Estimated Study Start Date  ICMJE January 15, 2021
Estimated Primary Completion Date December 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2018)
Changes in activation of mPFC, amygdala, and nucleus accumbens upon presentation of emotional faces. [ Time Frame: Initial Drug Dose, 2 weeks post drug dose (second drug dose). ]
This will be assessed using mixed effects regression models, with group, time, and group X time effects modeled to examine the effect of MDMA on region of interests (ROI) activation. We will also assess the functional connectivity of between these ROIs.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2018)
  • Changes in PTSD symptoms, which will be measured by The Clinician-Administered PTSD Scale 5 (CAPS-5). [ Time Frame: Baseline, Initial Drug Dose and Second Drug Dose, 24 hours and 1 week after initial and second drug dose. ]
    Assesses PTSD symptoms. It is a structured interview that consists of 30 items. Items are rated using a 0 to 4 severity scale. 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 (depersonalization and derealization. Higher scores indicate more severe PTSD symptoms.
  • Changes in depression symptoms, which will be measured by The Beck Depression Inventory II (BDI-II). [ Time Frame: Baseline, Initial Drug Does and Second Drug Dose, 24 hours after initial and second drug dose, 3 and 5 days after initial and second drug dose (by phone), 1 week after initial and second drug dose, 15, 17, 19, and 21 days after second drug dose (phone). ]
    Assesses depression symptoms. Consists of 21 items and uses a 0 to 3 severity scale. Total scores range from 0 to 63, with higher scores indicating more severe depression.
  • Changes in sleep patterns, which will be measured by The Pittsburgh Sleep Quality Index (PSQI). [ Time Frame: Baseline, 24 hours after first and second drug dose, 1 week after initial and second drug dose. ]
    Assesses the quality and patterns of sleep in adults. It differentiates "poor" from "good" sleep quality by measuring seven areas (components): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction over the last month. Items are rated using a 0 to 3 scale. The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality.
  • Changes in PTSD symptoms, which will be measured by The Posttraumatic Stress Disorder Checklist for the DSM-5 (PCL-5). [ Time Frame: Baseline, 24 hours after initial and second drug dose, 3 and 5 days after initial and second drug dose (phone), 1 week after initial and second drug dose, 15, 17, 19, and 21 days after second drug dose (phone). ]
    Assesses PTSD symptoms. It is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. Items are rated using a 0 to 4 scale. Total scores range from 0 to 80, with higher scores indicating more severe PTSD symptoms.
  • Changes in personality traits, which will be measured by The NEO Personality Inventory - Revised (NEO PI-R). [ Time Frame: Baseline, 1 week after initial and second drug dose. ]
    Assesses changes in personality traits. It is a personality inventory that examines a person's Big Five personality traits. It consist of 240 items that assess 30 specific traits, which in turn define the five factors: Neuroticism (N), Extraversion (E), Openness to Experience (O), Agreeableness (A), and Conscientiousness (C). Items are rated on a five-point Likert scale, from strongly disagree to strongly agree.
  • Changes in mental states, which will be measured The 5-Dimensional Altered States of Consciousness Scale (5D-ASC). [ Time Frame: Initial and second drug dose. ]
    Assesses different mental states induced by the interventions. Consists of 94 items which are rated by placing marks on a horizontal visual analogue scale (100 millimeters in length). The scale ranges from no, not more than usual (on the left) to yes, very much more than usual (on the right). The items are scored by measuring the millimeters from the low end of the scale to the participant's mark (from 0 to 100).
  • Changes in growth following a traumatic event, which will be measured by The Post traumatic Growth Inventory (PTGI). [ Time Frame: Baseline, 24 hours after initial and second drug dose, 1 week after initial and second drug dose. ]
    Assesses positive outcomes reported by persons who have experienced traumatic events. It is a 21-item scale that includes factors of New Possibilities, Relating to Others, Personal Strength, Spiritual Change, and Appreciation of Life. Participants are asked to rate the degree to which this change occurred in their life as a result of the crisis/disaster. Each item is rated from 0 (I did not experience this change as a result of my crisis) to 5 (I experienced this change to a very great degree as a result of my crisis). Total score is calculated by summing all items. Individual factors are scored by adding responses to items on each factor. Higher scores indicate greater growth.
  • Changes in well-being, which will be measured by The Well-Being Inventory (WBI). [ Time Frame: Baseline, 1 week after initial and second drug dose. ]
    Assesses well-being across life domains and such as work, finances, health, and social relationships. Participants are first asked questions about their level of functioning in each domain. Items are rated from 1 (never) to 5 (most or all of the time). Then they are asked questions about their satisfaction in each domain. Items are rated from 1 (very dissatisfied) to 5 (very satisfied). Higher total scores indicate greater well-being.
  • Changes in psychological inflexibility/experiential avoidance, which will be measured by The Acceptance and Action Questionnaire II (AAQ-II). [ Time Frame: Baseline, 1 Week after initial and second drug dose. ]
    Assesses psychological inflexibility/experiential avoidance. Participants are asked to rate how true each statement is for them. Items are rated from 1 (never true) to 7 (always true). Higher scores equal greater levels of psychological inflexibility.
  • Changes in emotional regulation, which will be measured by The Emotion Regulation Questionnaire (ERQ). [ Time Frame: Baseline, 1 week after initial and second drug dose. ]
    Assesses emotional regulation. A 10-item scale designed to measure respondents' tendency to regulate their emotions in two ways: (1) Cognitive Reappraisal and (2) Expressive Suppression. Participants answer each item on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). The higher the scores the greater the use of the emotion regulation strategy.
  • Changes in cognitive and emotional empathy, which will be measured by the Multifaceted Empathy Test (MET). [ Time Frame: Baseline, Initial and Second Drug Dose, 24 hours after initial and second drug dose, 1 week after initial and second drug dose. ]
    Measures cognitive and emotional empathy simultaneously and independently using a series of photorealistic stimuli computer based tasks.
  • Changes in the quality of specific relationships in terms of supportive and conflictual dynamics will be assessed with the Quality of Relationships Inventory (QRI) [ Time Frame: Baseline, Initial and Second Drug Dose, 1 week after initial and second drug dose. ]
    The 25 question task assesses the contemporary quality of specific relationships (between the patient and a specific individual, such as a family member) at a particular point in time in terms of conflict, support, and depth. It uses a Likert-type 4 point scale going from "1" indicating the item does not apply at all, while "4" indicates the item applies quite a lot.
  • Cognitive schemas about oneself and others, will be assessed by the Trauma and Attachment Beliefs Scale (TABS) [ Time Frame: Baseline ]
    The 84 item self-report scale, which measures responses on a 1-6 scale (1 = "Disagree Strongly, 6 = Agree Strongly) the degree to which respondents believe the statements correspond with their own beliefs. The measures of these beliefs relate to self-safety, other-safety, self-trust, other-trust, self-esteem, other-esteem, self-intimacy, other-intimacy, self-control, and other control.
  • Brain injury will be assessed for with the CogState Neuropsychological Test [ Time Frame: Baseline, 1 week after initial and second drug dose. ]
    Brain injuries associated with traumatic events, such as concussions, will be screened for in the CogState Neuropsychological Test, a standard computerized test used to assess neuropsychological deficits associated with brain injury.
  • Moral injury, or the sense of distress due to contradiction of deeply-held beliefs due to a traumatic event, will be measured by the Moral Injury Events Scale (MIES) [ Time Frame: Baseline, Initial and Second Drug Dose, 24 hours after initial and second drug dose, 1 week after initial and second drug dose. ]
    This 9 item self-report scale measures the moral injury, or distress due to the contradiction to a deeply-held belief about the world that often accompanies a traumatic incident. The injury is assessed in terms of "perceived transgression" and "perceived betrayal." Items are assessed with a Likert-type Scale (1 to 6, 1 = "strongly disagree," 6 = "strongly agree," with no neutral option). Higher scores indicate greater severity of associated event.
  • Changes in concept and sense of existential meaning will be measured with the Purpose and Meaning scale (PIL) [ Time Frame: Baseline, 1 week after second drug dose. ]
    Measures evaluation of the sense of existential purpose and enthusiasm for life in a three part self-report survey. Part A is a 20 point scale test which uses a 1-7 scale in which low number answers correspond attitudes such as boredom and directionless-ness. Parts B and C are not empirically useful, but ask for participants to completes sentences and compose a paragraph respectively. Higher scores indicate a greater existential sense of purpose, with scores above 113 indicate a high degree of purpose, scores below 92 suggesting a lack of purpose, and scores between 92 and 112 indicate moderate levels of purpose.
  • Changes in depression symptoms, which will be measured Montgomery-Asberg Depression Rating Scale (MADRS). [ Time Frame: Baseline, Initial and Second Drug Dose, 24 hours after initial and second drug dose, 1 week after initial and second administration. ]
    Assesses depression symptoms. Consists of 10 items and uses a 0 to 6 severity scale. Total scores range from 0 to 60, with higher scores indicating more severe depression.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effects of MDMA on Prefrontal and Amygdala Activation in PTSD.
Official Title  ICMJE The Effects of MDMA on Prefrontal and Amygdala Activation in Posttraumatic Stress Disorder
Brief Summary This study aims to investigate the effects of MDMA on prefrontal and amygdala activation, and to explore the relationship between these MDMA-induced neural changes and the acute behavioral effects of the drug in patients with PTSD.
Detailed Description

The investigators intend to utilize state-of-the-art validated Human Connectome Project (HCP) style approaches to determine the effects of MDMA on prefrontal and amygdala activation, and to explore the relationship between these MDMA-induced neural changes and the acute behavioral effects of the drug in patients with PTSD. In addition, the investigators will collect preliminary data on the MDMA effects on large-scale intrinsic functional connectivity using novel graph-based network analyses.

Specifically, the investigators will measure medial prefrontal cortex (mPFC) and amygdala activation in response to negative stimuli in patients with PTSD. The investigators hypothesize that MDMA will increase mPFC, but decrease amygdala, activation in response to negative stimuli.

The investigators will also explore the relationship between the MDMA-induced mPFC and amygdala activation, and performance on Ekman's Emotional Facial Expression task. This task is modulated by the mPFC and amygdala and as well as trauma severity in participants with PTSD. And finally, to explore the effects of MDMA on resting-state functional connectivity (rs-fcMRI) the investigators will use Coupled Intrinsic Connectivity Distribution (Coupled-ICD); an innovative, graph-based, fully data-driven approach that is particularly sensitive to paired rs-fcMRI data (e.g. pre/post-treatment).

Adult participants with PTSD will be recruited for a double-blind, placebo-controlled, within-subjects, crossover-dose neuroimaging study in which they will initially receive either a single dose of MDMA 1.5mg/kg or a placebo (niacin 250mg), with a crossover dose to follow. Doses will be separated by 2 weeks.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
This study will be a double-blind, placebo-controlled, within-subjects, crossover-dose neuroimaging study in which participants will initially receive either a single dose of MDMA 1.5mg/kg or a placebo (niacin 250mg), with a crossover dose to follow. Doses will be separated by 2 weeks.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Post Traumatic Stress Disorder
Intervention  ICMJE
  • Drug: MDMA
    A single dose of 1.5mg/kg will be administered once orally.
    Other Name: 3,4-Methylenedioxymethamphetamine
  • Drug: Niacin
    A single dose of 250mg will be administered once orally.
    Other Name: Nicotinic acid
Study Arms  ICMJE
  • Experimental: MDMA
    MDMA (1.5mg/kg)
    Intervention: Drug: MDMA
  • Placebo Comparator: Niacin
    Niacin (250mg)
    Intervention: Drug: Niacin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 21, 2018)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 15, 2021
Estimated Primary Completion Date December 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males or females between the ages of 21-55 years. Females will be included if they are not pregnant and agreed to utilize a medically (non-hormonal)* accepted birth control method (to include implant birth control, condom, diaphragm with spermicide, intrauterine device, tubal ligation, abstinence, or partner with vasectomy) or if post-menopausal for at least 1 year, or surgically sterile.
  • Able to provide written informed consent according to Yale HIC guidelines.
  • Able to read and write English as a primary language.
  • Diagnosis of PTSD, as determined by the Clinician Administered PTSD Scale (CAPS-5).
  • Must have a score of 23 or higher on the Clinician-Administered PTSD Scale (CAPS-5) at screening.
  • No more than mild TBI according to a modified version of the Brief TBI Screen.
  • Must not have a medical/neurological problem or use medication that would render MDMA unsafe by history or medical evaluation.
  • No prior exposure to MDMA.
  • Are willing to remain overnight at the study site after each experimental session.
  • Are willing to be driven home the day after the experimental sessions.
  • Not currently taking any of the listed medications at the time of the study.
  • Are willing to sign a medical release for the investigators to communicate directly with their therapist and doctors.
  • Are willing to abstain from alcohol, street drugs, and tobacco products while in the study.

Exclusion Criteria:

  • Patients with a diagnostic history of bipolar disorder, schizophrenia or schizoaffective disorder or currently exhibiting psychotic features as determined by the MINI 7.0 for the DSM-5.
  • Serious suicide or homicide risk, as assessed by evaluating clinician.
  • Substance abuse or dependence during the 6 months prior to screening; or a positive pre-study (screening) urine drug screen.
  • Any significant history of serious medical or neurological illness.
  • Any signs of major medical or neurological illness on examination or as a result of ECG screening or laboratory tests (e.g. positive urine tox, positive HIV/AIDS tests ).
  • Abnormality on physical examination. A participant with a clinical abnormality may be included only if the study physician considers the abnormality will not introduce additional risk factors and will not interfere with the study procedure.
  • Pregnant or lactating women or a positive urine pregnancy test for women of child-bearing potential at screening or prior to any imaging day.
  • Any history indicating learning disability, mental retardation, or attention deficit disorder.
  • Family history of cardiovascular diseases. History of hypertension with baseline blood pressure above 140 mmHg (systolic) and over 90 mmHg (diastolic). Any history of syncope and/or baseline blood pressure below 100mmHg (systolic).
  • History of claustrophobia.
  • BMI > 30 kg/m2 or >250 pounds.
  • Anxiolytic, neuroleptic and SRI medications (off SRIs for 4 weeks, fluoxetine 5 weeks).
  • Females taking hormonal contraceptives will not be able to participate in the study *(Hormonal contraceptives are exclusionary because MDMA increases production of oxytocin which is heavily modulated by other hormones (e.g. estrogen). Therefore, women need to be naturally cycling/ovulating and not taking any hormonal medications to participate in this study).
  • Any metal or electromagnetic implants, including: (Cardiac pacemaker, artificial heart valve, defibrillator, aneurysm clip, cochlear implants, shrapnel, neurostimulators, history of metal fragments in eyes or skin, significant hearing loss or other severe sensory impairment, a history of seizures or current use of anticonvulsants.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Giuliana DePalmer, MA 203-214-8276; 203-974-7680 giuliana.depalmer@yale.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03752918
Other Study ID Numbers  ICMJE 2000020348
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Benjamin Kelmendi, MD, Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Benjamin Kelmendi, MD Yale University
Study Director: Chadi Abdallah, MD Yale University
PRS Account Yale University
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP