Posttraumatic Stress Disorder
Conditions
Keywords
PTSD, Posttraumatic stress disorder, MDMA, psychotherapy, therapy
Brief summary
The goal of this clinical trial is to compare full dose MDMA-assisted therapy to placebo with therapy in participants with chronic, treatment-resistant PTSD. The main question it aims to answer is: Does MDMA-assisted therapy versus placebo with therapy reduce PTSD symptoms? Participants will receive either MDMA-assisted therapy or placebo with therapy during two blinded experimental sessions spaced three to five weeks apart. During experimental sessions, participants receive an initial dose of 125 mg of MDMA HCl, or placebo, followed by a dose of 62.5 mg of MDMA HCl, or placebo. During this treatment period, participants will also undergo non-drug preparatory therapy sessions and non-drug integration sessions. Researchers will compare PTSD symptoms in the MDMA-assisted therapy group to the placebo with therapy group to see if there is a reduction in symptoms after the treatment period. Safety measures will also be assessed between groups.
Detailed description
This randomized, double-blind, placebo-controlled clinical study will assess the safety and efficacy of MDMA-assisted therapy in treating chronic, treatment-resistant PTSD. In Stage 1, participants will be randomized to either MDMA-assisted therapy or placebo with therapy during two blinded experimental sessions, spaced three to five weeks apart. During experimental sessions, participants receive an initial dose of 125 mg of MDMA HCl, or placebo, followed by a dose of 62.5 mg of MDMA HCl, or placebo. During this treatment period, participants will also undergo non-drug preparatory therapy sessions and non-drug integration sessions. After this treatment period, participants will complete the primary endpoint assessment and the study will become unblinded. Participants who were assigned to receive MDMA-assisted therapy will receive a third session of MDMA-assisted therapy that is open-label and participants assigned to receive placebo with therapy will have the option to enter Stage 2. Stage 2 will explore the optimal therapeutic dose of MDMA in a clinical titration dosing strategy. Participants will receive MDMA-assisted with an initial dose of 100 mg followed by a dose of 50 mg of MDMA HCl for the first experimental session. In the second and third experimental sessions, participants will have the option to increase the dose to an initial dose of 125 mg followed by a dose of 62.5 mg. A blinded independent rater will assess PTSD symptoms via the CAPS-IV as well as other secondary outcome measures and safety measures.
Interventions
DRUGPlacebo
Placebo with therapy administered in two blinded experimental sessions. Participants in this group in Stage 1 may take part in Stage 2.
Participants will receive MDMA-assisted therapy during two blinded experimental sessions. After unblinding, may receive a third session of open-label MDMA-assisted therapy.
BEHAVIORALPsychotherapy
Psychotherapy before and after experimental sessions.
Sponsors
Lykos Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with moderate to severe PTSD; * Have chronic PTSD, defined as persisting for longer than 6 months; * Have treatment-resistant PTSD, meaning unable to achieve remission despite previous therapy or medication or discontinued treatment due to inability to tolerate previous therapy or medication; * Are willing to refrain from taking any psychiatric medications during the study period; * Willing to remain overnight at the study site; * Agree to have transportation home after experimental sessions; * Are willing to be contacted via telephone for all necessary telephone contacts; * Must have a negative pregnancy test if able to bear children, and agree to use an effective form of birth control; * Are proficient in speaking and reading English; * Agree not to participate in any other interventional clinical trials during the duration of this study.
Exclusion criteria
* Are pregnant or nursing, or if of child bearing potential, are not practicing an effective means of birth control; * Weigh less than 48 kg; * Are unable to give adequate informed consent; * Upon review of past and current drugs/medication must not be on or have taken a medication that is exclusionary; * Have used Ecstasy (illicit drug preparations purported to contain MDMA) more than five times in the last 10 years or at least once within six months of enrollment; * Upon review of medical or psychiatric history must not have any current or past diagnosis that would be considered a risk to participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinician-Administered PTSD Scale (CAPS-IV) Score From Baseline to Primary Endpoint | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) | Clinician-administered and scored assessment of PTSD symptoms via structured interview, including global symptom severity, dichotomous diagnostic score and subscale scores. The Clinician-Administered PTSD Scale for DSM-4 (CAPS-4) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-4. It contains symptom subscales, a CAPS-4 total severity score, and a diagnostic score. 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 in Beck Depression Inventory (BDI-II) Score From Baseline to Primary Endpoint | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) | The BDI-II is a validated 21-item self-report measure of symptoms of depression according to DSM-IV criteria. A BDI-II total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe depressive symptoms. The scores range from 0 to 63, with higher score indicating greater severity of depressive symptoms. |
| Change in Global Assessment of Functioning (GAF) Score From Baseline to Primary Endpoint | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) | The GAF Scale is a numeric scale ranging from 0 (serious risk of causing harm to the self or others) through 100 (superior function) that is used by mental health clinicians and physicians to subjectively rate the social, occupational, and psychological functioning of adults. The GAF is a reliable, validated measure of social functioning (Goldman, Skodol, and Lave, 1992). Higher scores indicate better functioning. |
| Change in PTSD Diagnostic Scale (PDS) Total Severity Score From Baseline to Primary Endpoint | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) | The PTSD Diagnostic Scale (PDS) is a 49 item self-report measure designed to follow DSM-IV criteria for assessing PTSD. The PDS consists of a checklist to identify potentially traumatizing events experienced by the respondent and respondents then indicate which of the experienced events has troubled them the most in the last month and rate their response to this event at the time of its occurrence. Respondents then rate the severity of 17 items representing the cardinal symptoms of PTSD experienced in the past 30 days on a scale from 0 (not at all) to 3 (5 or more times a week) as well as the level of impairment caused by their symptoms across nine areas of life functioning. The 17 symptom severity items are summed to create a total symptom severity score, which ranges from 0 to 51, with higher scores indicating greater symptom severity and/or frequency. |
| Change in Dissociation Experiences Scale II (DES-II) Total Score From Baseline to Primary Endpoint | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) | The DES-II is a 28-item self-report measure of dissociation, defined as a lack of normal integration of an individual's thoughts, feelings, or experiences into the stream of consciousness or memory. It is an established measure of dissociative symptoms. The scale consists of statements describing facets of dissociation. Respondents indicate how often the specific experience happens to them, from from never (0% of the time) to always (100%). The scale is scored by treating percentages as single digits and averaging to produce a total score, ranging from 0 to 100. The higher the score, the more dissociative symptoms. |
| Change in Posttraumatic Growth Inventory (PTGI) Total Score From Baseline to Primary Endpoint | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) | The PTGI is a 21-item self-report measure of perceived growth or benefits occurring after a traumatic event. It contains 5 subscales: relationship to others, new possibilities, personal strength, spiritual change, and appreciation of life. Responses to each question are made on a scale of 0 (no change) to 5 (great degree of change), with higher scores indicating greater personal growth. Items are added to calculate the total PTGI score which ranges from 0 to 105, with higher scores indicative of greater growth. |
| Change in Pittsburgh Sleep Quality Index (PSQI) Score From Baseline to Primary Endpoint | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) | The PSQI is a self-rated questionnaire which assesses sleep quality and disturbances. It is comprised of 19 items that yield 7 component scores. Component scores are summed to create a total score. Total scores range from 0 (better) to 21 (worse), with higher scores indicating poor sleep quality. |
Countries
Canada
Participant flow
Recruitment details
Participants were recruited through printed ads, internet ads, referrals from other psychiatrists, psychotherapists or physicians, and through word of mouth.
Participants by arm
| Arm | Count |
|---|---|
| Placebo With Therapy Participants will receive placebo with therapy during each of two blinded experimental sessions. | 2 |
| MDMA-assisted Therapy Participants will receive MDMA-assisted therapy during each of two blinded experimental sessions. | 4 |
| Total | 6 |
Baseline characteristics
| Characteristic | MDMA-assisted Therapy | Total | Placebo With Therapy |
|---|---|---|---|
| Age, Continuous | 49.6 years STANDARD_DEVIATION 7.9 | 47.7 years STANDARD_DEVIATION 8.82 | 44.0 years STANDARD_DEVIATION 12.66 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 4 | 0 / 2 | 0 / 2 | 0 / 4 |
| other Total, other adverse events | 2 / 2 | 4 / 4 | 2 / 2 | 2 / 2 | 4 / 4 |
| serious Total, serious adverse events | 0 / 2 | 0 / 4 | 0 / 2 | 0 / 2 | 0 / 4 |
Outcome results
Primary
Change in Clinician-Administered PTSD Scale (CAPS-IV) Score From Baseline to Primary Endpoint
Clinician-administered and scored assessment of PTSD symptoms via structured interview, including global symptom severity, dichotomous diagnostic score and subscale scores. The Clinician-Administered PTSD Scale for DSM-4 (CAPS-4) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-4. It contains symptom subscales, a CAPS-4 total severity score, and a diagnostic score. 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 Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo With Therapy | Change in Clinician-Administered PTSD Scale (CAPS-IV) Score From Baseline to Primary Endpoint | -21.5 score on a scale | Standard Deviation 12.02 |
| MDMA-assisted Therapy | Change in Clinician-Administered PTSD Scale (CAPS-IV) Score From Baseline to Primary Endpoint | -17.3 score on a scale | Standard Deviation 13.05 |
Secondary
Change in Beck Depression Inventory (BDI-II) Score From Baseline to Primary Endpoint
The BDI-II is a validated 21-item self-report measure of symptoms of depression according to DSM-IV criteria. A BDI-II total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe depressive symptoms. The scores range from 0 to 63, with higher score indicating greater severity of depressive symptoms.
Time frame: Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo With Therapy | Change in Beck Depression Inventory (BDI-II) Score From Baseline to Primary Endpoint | -4.0 score on a scale | Standard Deviation 2.83 |
| MDMA-assisted Therapy | Change in Beck Depression Inventory (BDI-II) Score From Baseline to Primary Endpoint | 2.0 score on a scale | Standard Deviation 15.34 |
Secondary
Change in Dissociation Experiences Scale II (DES-II) Total Score From Baseline to Primary Endpoint
The DES-II is a 28-item self-report measure of dissociation, defined as a lack of normal integration of an individual's thoughts, feelings, or experiences into the stream of consciousness or memory. It is an established measure of dissociative symptoms. The scale consists of statements describing facets of dissociation. Respondents indicate how often the specific experience happens to them, from from never (0% of the time) to always (100%). The scale is scored by treating percentages as single digits and averaging to produce a total score, ranging from 0 to 100. The higher the score, the more dissociative symptoms.
Time frame: Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
Population: DES-II data was not collected in one MDMA participant at the endpoint assessment so is excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo With Therapy | Change in Dissociation Experiences Scale II (DES-II) Total Score From Baseline to Primary Endpoint | 8.4 score on a scale | Standard Deviation 3.79 |
| MDMA-assisted Therapy | Change in Dissociation Experiences Scale II (DES-II) Total Score From Baseline to Primary Endpoint | -4.6 score on a scale | Standard Deviation 13.63 |
Secondary
Change in Global Assessment of Functioning (GAF) Score From Baseline to Primary Endpoint
The GAF Scale is a numeric scale ranging from 0 (serious risk of causing harm to the self or others) through 100 (superior function) that is used by mental health clinicians and physicians to subjectively rate the social, occupational, and psychological functioning of adults. The GAF is a reliable, validated measure of social functioning (Goldman, Skodol, and Lave, 1992). Higher scores indicate better functioning.
Time frame: Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo With Therapy | Change in Global Assessment of Functioning (GAF) Score From Baseline to Primary Endpoint | 5.0 score on a scale | Standard Deviation 4.24 |
| MDMA-assisted Therapy | Change in Global Assessment of Functioning (GAF) Score From Baseline to Primary Endpoint | 5.3 score on a scale | Standard Deviation 3.86 |
Secondary
Change in Pittsburgh Sleep Quality Index (PSQI) Score From Baseline to Primary Endpoint
The PSQI is a self-rated questionnaire which assesses sleep quality and disturbances. It is comprised of 19 items that yield 7 component scores. Component scores are summed to create a total score. Total scores range from 0 (better) to 21 (worse), with higher scores indicating poor sleep quality.
Time frame: Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo With Therapy | Change in Pittsburgh Sleep Quality Index (PSQI) Score From Baseline to Primary Endpoint | 1.0 score on a scale | Standard Deviation 1.41 |
| MDMA-assisted Therapy | Change in Pittsburgh Sleep Quality Index (PSQI) Score From Baseline to Primary Endpoint | -3.5 score on a scale | Standard Deviation 3.32 |
Secondary
Change in Posttraumatic Growth Inventory (PTGI) Total Score From Baseline to Primary Endpoint
The PTGI is a 21-item self-report measure of perceived growth or benefits occurring after a traumatic event. It contains 5 subscales: relationship to others, new possibilities, personal strength, spiritual change, and appreciation of life. Responses to each question are made on a scale of 0 (no change) to 5 (great degree of change), with higher scores indicating greater personal growth. Items are added to calculate the total PTGI score which ranges from 0 to 105, with higher scores indicative of greater growth.
Time frame: Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
Population: PTGI data was not collected in one MDMA participant at the endpoint assessment so is excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo With Therapy | Change in Posttraumatic Growth Inventory (PTGI) Total Score From Baseline to Primary Endpoint | 8.5 score on a scale | Standard Deviation 14.85 |
| MDMA-assisted Therapy | Change in Posttraumatic Growth Inventory (PTGI) Total Score From Baseline to Primary Endpoint | -3.7 score on a scale | Standard Deviation 11.85 |
Secondary
Change in PTSD Diagnostic Scale (PDS) Total Severity Score From Baseline to Primary Endpoint
The PTSD Diagnostic Scale (PDS) is a 49 item self-report measure designed to follow DSM-IV criteria for assessing PTSD. The PDS consists of a checklist to identify potentially traumatizing events experienced by the respondent and respondents then indicate which of the experienced events has troubled them the most in the last month and rate their response to this event at the time of its occurrence. Respondents then rate the severity of 17 items representing the cardinal symptoms of PTSD experienced in the past 30 days on a scale from 0 (not at all) to 3 (5 or more times a week) as well as the level of impairment caused by their symptoms across nine areas of life functioning. The 17 symptom severity items are summed to create a total symptom severity score, which ranges from 0 to 51, with higher scores indicating greater symptom severity and/or frequency.
Time frame: Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session)
Population: One participant in the MDMA group did not provide PDS data at Primary Endpoint so is excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo With Therapy | Change in PTSD Diagnostic Scale (PDS) Total Severity Score From Baseline to Primary Endpoint | -1.0 score on a scale | Standard Deviation 5.66 |
| MDMA-assisted Therapy | Change in PTSD Diagnostic Scale (PDS) Total Severity Score From Baseline to Primary Endpoint | -5.3 score on a scale | Standard Deviation 1.53 |