PTSD
Conditions
Brief summary
The goal of this clinical trial is to learn if MDMA-assisted therapy is effective in U.S. military veterans with at least moderate chronic PTSD. The main question it aims to answer is: Are two versus three MDMA-assisted therapy sessions in an outpatient treatment clinic more effective? Researchers will compare two MDMA-assisted therapy sessions to three MDMA-assisted therapy sessions. Participants will undergo three non-drug preparatory sessions prior to their first MDMA-assisted therapy session. Each MDMA-assisted therapy session will be followed by three non-drug integrative therapy sessions.
Detailed description
This open-label, randomized study will assess the comparative effectiveness of two versus three active MDMA-assisted therapy sessions in U.S. military veterans with at least moderate chronic PTSD treated in an outpatient VA treatment clinic. The study will be conducted in up to 60 participants. Prior to the randomized portion of the study, each therapist pair team will treat one participant under the 3-session model, and one participant under the 2-session model. In total, 8 participants will be treated under this proof of principle therapist training lead-in. A 120 mg dose of MDMA, followed by a supplemental dose (60 mg) unless contraindicated, is administered during the treatment period with manualized psychotherapy in 2 or 3 open-label monthly Experimental Sessions. This \ 8-12-week Treatment Period includes three Preparatory Sessions prior to the first MDMA-assisted session. During the treatment period, each Experimental Session is followed by three Integrative Sessions of non-drug therapy. The Primary Outcome measure, the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), is assessed by a centralized, blinded Independent Rater (IR) pool at post-treatment for each group.
Interventions
DRUGMidomafetamine
120 mg midomafetamine HCl followed by a supplemental dose of 60 mg
BEHAVIORALPsychotherapy
Manualized psychotherapy performed by therapist team
Sponsors
Lykos Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* U.S. military veteran * Are at least 18 years old. * Are fluent in speaking and reading the predominantly used or recognized language of the study site. * Are able to swallow pills. * 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. * At baseline, have moderate PTSD diagnosis.
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. * 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; or have previously participated in a MAPS-sponsored MDMA clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score From Baseline to Primary Outcome | 2 Session Group: ~12 weeks from baseline to primary outcome; 3 Session Group: ~16 weeks from baseline to primary outcome | The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a 30-item semi-structured interview assessing PTSD in the past month through diagnostic and symptom severity scores anchored to a DSM-5 defined traumatic event. The CAPS-5 produces a Total Severity Score based on severity of PTSD domains described in the DSM-5, as well as a categorical rating indicating whether a participant meets PTSD diagnostic criteria. CAPS-5 Total Symptom Severity scores range from 0 to 80 with higher values indicating greater symptom severity. CAPS-5 assigns PTSD diagnosis as being present or absent. |
| Change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score From Baseline to Secondary Outcome Timepoint in the 2 Session Group | ~16 weeks from baseline to secondary outcome (note: secondary outcome timepoint assessed in 2 session group to evaluate the primary outcome measure in a follow up period equivalent to that of the 3 session group in the primary analysis.) | The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a 30-item semi-structured interview assessing PTSD in the past month through diagnostic and symptom severity scores anchored to a DSM-5 defined traumatic event. The CAPS-5 produces a Total Severity Score based on severity of PTSD domains described in the DSM-5, as well as a categorical rating indicating whether a participant meets PTSD diagnostic criteria. CAPS-5 Total Symptom Severity scores range from 0 to 80 with higher values indicating greater symptom severity. CAPS-5 assigns PTSD diagnosis as being present or absent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sheehan Disability Scale (SDS) Total Score From Baseline to Primary Outcome | 2 Session Group: ~12 weeks from baseline to primary outcome; 3 Session Group: ~16 weeks from baseline to primary outcome | The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional 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'). SDS scoring was adapted for the purposes of this study to limit missing item-level data through averaging the three domain scores to produce a total score, as well as imputation of work-related impairment score in the case of participants who did not work during the reporting period based on the reason for not working. The SDS total score and each of the domain sub-scores range from 0 to 10, with higher scores indicating greater functional impairment. |
| Change in Sheehan Disability Scale (SDS) Total Score From Baseline to Secondary Outcome Timepoint in the 2 Session Group | ~16 weeks from baseline to secondary outcome (note: secondary outcome timepoint assessed in 2 session group to evaluate the primary outcome measure in a follow up period equivalent to that of the 3 session group in the primary analysis.) | Sheehan Disability Scale (SDS) total score, a measure of clinician-rated functional impairment. The items indicate degree of impairment in the domains of work/school, social life, and home life, with response options based on an eleven-point scale (0=not at all to 10=extremely), and five verbal tags (not at all, mildly, moderately, markedly, extremely). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Two Sessions of MDMA-assisted Therapy Two experimental sessions of MDMA-assisted therapy
Midomafetamine: 120 mg midomafetamine HCl followed by a supplemental dose of 60 mg
Psychotherapy: Manualized psychotherapy performed by therapist team | 13 |
| Three Sessions of MDMA-assisted Therapy Three experimental sessions of MDMA-assisted therapy
Midomafetamine: 120 mg midomafetamine HCl followed by a supplemental dose of 60 mg
Psychotherapy: Manualized psychotherapy performed by therapist team | 10 |
| Total | 23 |
Baseline characteristics
| Characteristic | Two Sessions of MDMA-assisted Therapy | Three Sessions of MDMA-assisted Therapy | Total |
|---|---|---|---|
| Age, Continuous | 41.6 years STANDARD_DEVIATION 6.23 | 38.3 years STANDARD_DEVIATION 5.06 | 40.2 years STANDARD_DEVIATION 5.87 |
| Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Score | 37.1 score on a scale STANDARD_DEVIATION 6.38 | 43.8 score on a scale STANDARD_DEVIATION 7.71 | 40.0 score on a scale STANDARD_DEVIATION 7.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 6 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 9 Participants | 8 Participants | 17 Participants |
| Region of Enrollment United States | 13 participants | 10 participants | 23 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 12 Participants | 10 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 10 |
| other Total, other adverse events | 13 / 13 | 10 / 10 |
| serious Total, serious adverse events | 0 / 13 | 0 / 10 |
Outcome results
Primary
Change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score From Baseline to Primary Outcome
The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a 30-item semi-structured interview assessing PTSD in the past month through diagnostic and symptom severity scores anchored to a DSM-5 defined traumatic event. The CAPS-5 produces a Total Severity Score based on severity of PTSD domains described in the DSM-5, as well as a categorical rating indicating whether a participant meets PTSD diagnostic criteria. CAPS-5 Total Symptom Severity scores range from 0 to 80 with higher values indicating greater symptom severity. CAPS-5 assigns PTSD diagnosis as being present or absent.
Time frame: 2 Session Group: ~12 weeks from baseline to primary outcome; 3 Session Group: ~16 weeks from baseline to primary outcome
Population: One participant in the 3 session group did not complete the primary outcome assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Two Sessions of MDMA-assisted Therapy | Change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score From Baseline to Primary Outcome | -20.5 score on a scale | Standard Deviation 9.38 |
| Three Sessions of MDMA-assisted Therapy | Change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score From Baseline to Primary Outcome | -18.0 score on a scale | Standard Deviation 13.92 |
Primary
Change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score From Baseline to Secondary Outcome Timepoint in the 2 Session Group
The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a 30-item semi-structured interview assessing PTSD in the past month through diagnostic and symptom severity scores anchored to a DSM-5 defined traumatic event. The CAPS-5 produces a Total Severity Score based on severity of PTSD domains described in the DSM-5, as well as a categorical rating indicating whether a participant meets PTSD diagnostic criteria. CAPS-5 Total Symptom Severity scores range from 0 to 80 with higher values indicating greater symptom severity. CAPS-5 assigns PTSD diagnosis as being present or absent.
Time frame: ~16 weeks from baseline to secondary outcome (note: secondary outcome timepoint assessed in 2 session group to evaluate the primary outcome measure in a follow up period equivalent to that of the 3 session group in the primary analysis.)
Population: One participant in the 2 session group did not complete the CAPS-5 at the secondary outcome timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Two Sessions of MDMA-assisted Therapy | Change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score From Baseline to Secondary Outcome Timepoint in the 2 Session Group | -24.9 score on a scale | Standard Deviation 8.73 |
Secondary
Change in Sheehan Disability Scale (SDS) Total Score From Baseline to Primary Outcome
The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional 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'). SDS scoring was adapted for the purposes of this study to limit missing item-level data through averaging the three domain scores to produce a total score, as well as imputation of work-related impairment score in the case of participants who did not work during the reporting period based on the reason for not working. The SDS total score and each of the domain sub-scores range from 0 to 10, with higher scores indicating greater functional impairment.
Time frame: 2 Session Group: ~12 weeks from baseline to primary outcome; 3 Session Group: ~16 weeks from baseline to primary outcome
Population: One participant in the 3 session group did not complete the secondary outcome assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Two Sessions of MDMA-assisted Therapy | Change in Sheehan Disability Scale (SDS) Total Score From Baseline to Primary Outcome | -2.9 score on a scale | Standard Deviation 2.3 |
| Three Sessions of MDMA-assisted Therapy | Change in Sheehan Disability Scale (SDS) Total Score From Baseline to Primary Outcome | -1.6 score on a scale | Standard Deviation 3.49 |
Secondary
Change in Sheehan Disability Scale (SDS) Total Score From Baseline to Secondary Outcome Timepoint in the 2 Session Group
Sheehan Disability Scale (SDS) total score, a measure of clinician-rated functional impairment. The items indicate degree of impairment in the domains of work/school, social life, and home life, with response options based on an eleven-point scale (0=not at all to 10=extremely), and five verbal tags (not at all, mildly, moderately, markedly, extremely).
Time frame: ~16 weeks from baseline to secondary outcome (note: secondary outcome timepoint assessed in 2 session group to evaluate the primary outcome measure in a follow up period equivalent to that of the 3 session group in the primary analysis.)
Population: One participant in the 2 session group did not complete the SDS at the secondary outcome timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Two Sessions of MDMA-assisted Therapy | Change in Sheehan Disability Scale (SDS) Total Score From Baseline to Secondary Outcome Timepoint in the 2 Session Group | -4.1 score on a scale | Standard Deviation 2.39 |