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Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Therapy for Treatment of PTSD

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ClinicalTrials.gov Identifier: NCT03282123
Recruitment Status : Completed
First Posted : September 13, 2017
Results First Posted : July 29, 2021
Last Update Posted : July 29, 2021
Sponsor:
Information provided by (Responsible Party):
Multidisciplinary Association for Psychedelic Studies

Tracking Information
First Submitted Date  ICMJE September 11, 2017
First Posted Date  ICMJE September 13, 2017
Results First Submitted Date  ICMJE July 8, 2021
Results First Posted Date  ICMJE July 29, 2021
Last Update Posted Date July 29, 2021
Actual Study Start Date  ICMJE October 24, 2017
Actual Primary Completion Date August 10, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 8, 2021)
Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores [ Time Frame: Baseline to 18 weeks post-enrollment ]
The Clinician-Administered PTSD Scale for DSM-V (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. 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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2017)
Change from Baseline in Clinician Administered PTSD Scale for DSM-5 [ Time Frame: 18 weeks post-enrollment ]
Global severity Scores on the CAPS-5, a measure of PTSD symptoms
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2021)
Change From Baseline to Visit 19 in Adapted SDS Total Score [ Time Frame: Baseline to 18 weeks post-enrollment ]
The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment that was adapted for the purposes of this study to limit missing item-level data as per the FDA requirements and included use of the three-item mean as the total score and imputation of work-related impairment. The SDS is a 3-item scale measuring the severity of disability in the domains of work, family life/home responsibilities and social/leisure activities, with each item scored on a ten-point Likert scale from 0 ('not at all impaired') to 10 ('very severely impaired'). The SDS total score was the mean of the 3 item responses. The SDS total score ranged from 0 to 10, with higher scores indicating greater functional impairment.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2017)
  • Change from Baseline in Beck Depression Inventory II (BDI-II) [ Time Frame: 18 weeks post-enrollment ]
    Assesses self-reported depression symptoms
  • Change from baseline in Pittsburgh Sleep Quality Index [ Time Frame: 18 weeks post-enrollment ]
    Assesses self-reported sleep quality
  • Systolic blood pressure (SBP) [ Time Frame: Seven weeks after enrollment ]
    Systolic blood pressure assessed 1.5 to 2 hours after initial MDMA dose
  • Systolic blood pressure (SBP) [ Time Frame: 11 weeks after enrollment ]
    Systolic blood pressure assessed 1.5 to 2 hours after initial MDMA dose
  • Systolic blood pressure (SBP) [ Time Frame: 15 weeks after enrollment ]
    Systolic blood pressure assessed 1.5 to 2 hours after initial MDMA dose
  • Diastolic blood pressure (DBP) [ Time Frame: Seven weeks after enrollment ]
    Diastolic blood pressure assessed 1.5 to 2 hours after initial MDMA dose
  • Diastolic blood pressure (DBP) [ Time Frame: 11 weeks after enrollment ]
    Diastolic blood pressure assessed 1.5 to 2 hours after initial MDMA dose
  • Diastolic blood pressure (DBP) [ Time Frame: 15 weeks after enrollment ]
    Diastolic blood pressure assessed 1.5 to 2 hours after initial MDMA dose
  • Pulse [ Time Frame: Seven weeks after enrollment ]
    Pulse assessed 1.5 to 2 hours after initial MDMA dose
  • Pulse [ Time Frame: 11 weeks after enrollment ]
    Pulse assessed 1.5 to 2 hours after initial MDMA dose
  • Pulse [ Time Frame: 15 weeks after enrollment ]
    Pulse assessed 1.5 to 2 hours after initial MDMA dose
  • Body temperature (BT) [ Time Frame: Seven weeks after enrollment ]
    BT assessed 1.5 to 2 hours after initial MDMA dose
  • Body temperature (BT) [ Time Frame: 11 weeks after enrollment ]
    BT assessed 1.5 to 2 hours after initial MDMA dose
  • Body temperature (BT) [ Time Frame: 15 weeks after enrollment ]
    BT assessed 1.5 to 2 hours after initial MDMA dose
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Therapy for Treatment of PTSD
Official Title  ICMJE An Open-Label, Multi-Site Phase 2 Study of the Safety and Effect of Manualized MDMA-Assisted Therapy for the Treatment of Severe Posttraumatic Stress Disorder
Brief Summary

This multi-site, open-label, Phase 2, lead-in study assesses the safety and effect of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy in participants diagnosed with at least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified and trained to work on the sponsor's planned Phase 3 studies will treat at least one open-label participant in this study.

This study will compare the effects of three open-label manualized Experimental Sessions of therapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a supplemental half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg. This ~12-week Treatment Period is preceded by three Preparatory Sessions. During the Treatment Period, each Experimental Session is followed by three Integrative Sessions of non-drug psychotherapy. The Primary Outcome measure is the change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) total severity scores from Baseline to Primary Endpoint (Visit 19).

Detailed Description

PTSD is a serious debilitating disorder that negatively impacts a person's daily life. PTSD is a stress-related psychiatric condition that may occur following a traumatic event such as war, disaster, sexual abuse, violence, terrorism, and accidents. PTSD negatively impacts a person's daily life, resulting in relationship difficulties, difficulty in finding and maintaining a job, reduced cognitive and psychosocial functioning, substance abuse, high-cost healthcare use, and increased depression and suicide risk. Available PTSD treatments, including medications and therapy, effectively treat only a fraction of people who try them for adequate dose and duration. People with PTSD can be treated with psychotherapies and pharmacotherapies. In the past decade, there has been a growing amount of research into medications and other methods that may augment the effectiveness of psychotherapy for PTSD

3,4-methylenedioxymethamphetamine is a drug that releases serotonin, norepinephrine and dopamine in the brain and indirectly increases levels of the neurohormones oxytocin, arginine vasopressin and cortisol. The combined neurobiological effects of MDMA increase compassion, reduce defenses and fear of emotional injury, and enhance communication and introspection. MDMA produces anxiolytic and prosocial effects, which counteract avoidance and hyperarousal in the context of therapy. A combined treatment of MDMA and therapy may be especially useful for treating PTSD.

This multi-site, open-label, Phase 2, lead-in study assesses the safety and effect of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy in participants diagnosed with at least severe posttraumatic stress disorder (PTSD). Therapy teams that have been identified and trained to work on the sponsor's planned Phase 3 studies will treat at least one open-label participant in this study.

This study will compare the effects of three open-label manualized Experimental Sessions of psychotherapy assisted by flexible doses of MDMA. Initial doses per Experimental Session include 80 mg or 120 mg of MDMA compounded with lactose, followed 1.5 to 2 hours later by a supplemental half-dose (40 mg or 60 mg). Total amounts of MDMA to be administered per Experimental Session range from 80 mg to 180 mg. This ~12-week Treatment Period is preceded by three Preparatory Sessions. During the Treatment Period, each Experimental Session is followed by three Integrative Sessions of non-drug psychotherapy. The Primary Outcome measure is the change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) from Baseline to Primary Endpoint (Visit 19).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Three sessions of MDMA-assisted therapy with flexible dose of MDMA (80 to 120 mg with optional supplemental half-dose)
Masking: None (Open Label)
Masking Description:
This study will be open label
Primary Purpose: Treatment
Condition  ICMJE PTSD
Intervention  ICMJE
  • Drug: MDMA
    80 to 120 mg MDMA
    Other Name: 3,4-methylenedioxymethamphetamine
  • Behavioral: Therapy
    Non-directive therapy conducted during MDMA-assisted therapy session
Study Arms  ICMJE Experimental: MDMA-assisted therapy
Three sessions of MDMA-assisted therapy with flexible dose of MDMA from 80 to 120 mg and optional supplemental dose half that of initial dose 1.5 to 2 hours later
Interventions:
  • Drug: MDMA
  • Behavioral: Therapy
Publications * Not Provided

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: April 9, 2019)
38
Original Estimated Enrollment  ICMJE
 (submitted: September 12, 2017)
60
Actual Study Completion Date  ICMJE August 10, 2019
Actual Primary Completion Date August 10, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Are at least 18 years old
  • Are fluent in speaking and reading the predominantly used or recognized language of the study site
  • Agree to have study visits recorded, including Experimental Sessions, Independent Rater assessments, and non-drug psychotherapy sessions
  • Must provide a contact (relative, spouse, close friend or other caregiver) 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

  • If of childbearing potential, must have a 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.
  • Must not participate in any other interventional clinical trials during the duration of the study,
  • Must be willing to remain overnight at the study site after each Experimental Session and be driven home after, and commit to medication dosing, therapy, and study procedures
  • Meet DSM-5 Criteria for Severe PTSD

Exclusion Criteria:

  • Are not able to give adequate informed consent
  • Have uncontrolled hypertension
  • Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds [ms] corrected by Bazett's formula)
  • Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
  • Have evidence or history of significant medical disorders
  • Have symptomatic liver disease
  • Have history of hyponatremia or hyperthermia
  • Weigh less than 48 kilograms (kg)
  • Are pregnant or nursing, or are of childbearing potential and are not practicing an effective means of birth control.
  • Are abusing illegal drugs
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03282123
Other Study ID Numbers  ICMJE MP-16
Has Data Monitoring Committee No
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: Yes
Plan Description: We will share outcome data appearing in any published reports upon request.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Time Frame: Data and study-related documents will be available wehn all participants have completed the study
Access Criteria: Interested persons should correspond with the central contact for the multi-site study.
Responsible Party Multidisciplinary Association for Psychedelic Studies
Study Sponsor  ICMJE Multidisciplinary Association for Psychedelic Studies
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Michael C Mithoefer, MD MAPS Public Benefit Corp.
PRS Account Multidisciplinary Association for Psychedelic Studies
Verification Date July 2021

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