PTSD
Conditions
Keywords
MDMA, methylenedioxymethamphetamine, therapy, midomafetamine
Brief summary
The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people diagnosed with at least severe PTSD. The main question it aims to answer is: Do three open-label sessions of MDMA-assisted therapy reduce PTSD symptoms? Participants will receive three non-drug preparatory sessions followed by three sessions of MDMA-assisted therapy. Each MDMA-assisted therapy session is followed by three non-drug integrative therapy sessions.
Detailed description
This multi-site, open-label, Phase 2, lead-in study assesses the safety and efficacy of 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).
Interventions
DRUGMidomafetamine
80 to 120 mg MDMA
BEHAVIORALManualized therapy
Non-directive therapy conducted during MDMA-assisted therapy session
Sponsors
Lykos Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This study will be open label
Intervention model description
Three sessions of MDMA-assisted therapy with flexible dose of MDMA (80 to 120 mg with optional supplemental half-dose)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. * Meet DSM-5 criteria for active substance use disorder for any substance other than caffeine or nicotine * Have used Ecstasy (material represented as containing MDMA) more than 10 times within the last 10 years or at least once within 6 months of the first Experimental Session.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Visit 19 in Adapted SDS Total Score | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited through print and internet advertisements, referrals from other psychiatrists, psychotherapists, or physicians, and by word of mouth. The sponsor monitored demographics on an ongoing basis and encouraged diversity in enrollment by communicating with sites
Participants by arm
| Arm | Count |
|---|---|
| MDMA-assisted Psychotherapy Three sessions of MDMA-assisted psychotherapy 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
MDMA: 80 to 120 mg MDMA
Psychotherapy: Non-directive psychotherapy conducted during MDMA-assisted psychotherapy session | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | MDMA-assisted Psychotherapy |
|---|---|
| Age, Continuous | 36.42 years STANDARD_DEVIATION 11.09 |
| Baseline CAPS-5 Total Severity Score | 45.4 score on a scale STANDARD_DEVIATION 6.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 33 |
| other Total, other adverse events | 33 / 33 |
| serious Total, serious adverse events | 1 / 33 |
Outcome results
Primary
Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores
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.
Time frame: Baseline to 18 weeks post-enrollment
Population: Safety Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MDMA-assisted Therapy | Change From Baseline to Visit 19 in CAPS-5 Total Severity Scores | -30.49 score on a scale |
Secondary
Change From Baseline to Visit 19 in Adapted SDS Total Score
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.
Time frame: Baseline to 18 weeks post-enrollment
Population: Safety Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MDMA-assisted Therapy | Change From Baseline to Visit 19 in Adapted SDS Total Score | -4.88 score on a scale |