Posttraumatic Stress Disorder
Conditions
Keywords
PTSD, MDMA, psychotherapy, Switzerland
Brief summary
This study will examine MDMA-assisted psychotherapy in individuals aged 18 years or older diagnosed with PTSD, with PTSD symptoms not improving after trying at least one treatment. This objective of this study is to determine whether three eight-hour long sessions of MDMA-assisted psychotherapy, scheduled three to five weeks apart, can be safely administered to participants with PTSD, and whether combining a fully therapeutic dose of MDMA with psychotherapy, when compared with a low (active placebo) dose of MDMA, will reduce PTSD symptoms. Participants will be randomly assigned to receive the full dose of MDMA (125 mg) or assigned to receive a low or active placebo dose of MDMA (25 mg) during each of three experimental sessions.
Detailed description
Posttraumatic stress disorder (PTSD) occurs after experiencing a traumatic event or events. PTSD is a public health problem that causes a great deal of suffering. This study will examine MDMA-assisted psychotherapy in individuals aged 18 years or older diagnosed with PTSD, with PTSD symptoms not improving after trying at least one treatment. This objective of this study is to determine whether three eight-hour long sessions of MDMA-assisted psychotherapy, scheduled three to five weeks apart, can be safely administered to participants with PTSD, and whether combining a fully therapeutic dose of MDMA with psychotherapy, when compared with a low (active placebo) dose of MDMA, will reduce PTSD symptoms. Participants will be randomly assigned to receive the full dose of MDMA (125 mg) or assigned to receive a low or active placebo dose of MDMA (25 mg) during each of three experimental sessions. People who receive the low dose of MDMA have the opportunity to take part in a second open label study continuation, wherein the participants will undergo three MDMA-assisted sessions, with the participant and the researchers knowing that a full dose of MDMA is being administered. People who receive the full dose of MDMA, and any person who received low-dose MDMA and does not undergo the open-label study continuation will have PTSD symptoms measured six and twelve months after the third session. People who take part in the open label study continuation have their PTSD symptoms assessed six and 12 months after the third Phase II MDMA-assisted session.
Interventions
DRUG3,4-methylenedioxymethamphetamine (125 mg)
Participants will receive an initial dose of 125 mg MDMA orally and, if investigator and participant deem appropriate, 2.5 hours later they will receive 62.5 mg MDMA orally.
DRUG3,4-methyelendioxymethamphetamine (25 mg)
Participants will receive a 25 mg MDMA orally, and if investigator and participant agree, 2.5 hours later they will receive 12.5 mg MDMA orally.
BEHAVIORALTherapy
Non-directive therapy performed by a team of two co-therapists
Sponsors
Swiss Medical Society for Psycholytic Therapy
Lykos Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with posttraumatic stress disorder (PTSD). * PTSD still remains after one or more prior treatment, with treatment including psychotherapy (talk therapy) or drug therapy * May meet criteria for a mood disorder * Must be at least 18 years old * Must be able to stop taking psychiatric medication during the course of the study, from the start of the study to the follow-up two months after experimental session 3. * Must agree to follow all rules and instructions relating to the experimental session, including restrictions on food and substance (alcohol and drug) consumption. * Must be willing to stay overnight at the researcher's office after each experimental session until the non-drug session occurring the next morning. * Must be willing to be contacted by one of the researchers on a daily basis for a week after each experimental session. * Female participants of childbearing potential must have a negative pregnancy test and must agree to use an effective form of birth control. * Participants must have sufficient proficiency in speaking the German language to participate in MDMA-assisted psychotherapy. Participants must be able to read documents in German.
Exclusion criteria
* Cannot have history of or current primary psychotic disorder or bipolar affective disorder-1. * Dissociative identity disorder, or an eating disorder with active purging or borderline personality disorder. * Evidence or history of significant hematological, endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, renal, gastrointestinal, immunocompromising, or neurological disease, including seizure disorder. (People with hypothyroidism who are on adequate and stable thyroid replacement will not be excluded). * Uncontrolled hypertension, peripheral vascular disease, hepatic disease (with or without abnormal liver enzymes), or history of hyponatremia or hyperthermia. * Being pregnant or lactating (nursing), or not practicing an effective method of birth control. * Weight of less than 50 or more than 105 kg. * Patients reporting prior use of Ecstasy more than 5 times or at any time within the previous 6 months. * People who would present a serious suicide risk or who are likely to require hospitalization during the course of the study. * People who need ongoing concomitant therapy with a psychotropic drug. * Meeting DSM-IV criteria for substance abuse or dependence for any substance save caffeine or nicotine in the past 60 days. * People who cannot give adequate consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Primary Endpoint in Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) | Less than 4 weeks before first experimental session (Baseline) to 3 weeks post 3rd experimental session (Primary Endpoint) | The CAPS-IV is a structured clinical interview designed to assess the symptoms and severity of PTSD. The CAPS-IV provides a means to evaluate the frequency and intensity dimensions of each symptom, the impact of symptoms on the patient's social and occupational functioning, the overall severity of the symptom complex, global improvement since baseline, and the validity of the ratings obtained. Total severity scores range from 0 to 136, with higher scores indicating greater severity of PTSD symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Primary Endpoint in Posttraumatic Stress Diagnostic Scale (PDS) | Less than 4 weeks before first experimental session (Baseline) to 3 weeks post 3rd experimental session (Primary Endpoint) | The Posstraumatic Stress Diagnostic Scale (PSD) is a 49-item self-report instrument to aid in the diagnosis of PTSD. Questions are asked about symptoms experienced and participants respond on a scale from 0 (not at all or only one time) to 3 (5 or more times a week/almost always). Items are summed to create a total score that ranges from 0 to 51, with higher scores indicating more PTSD symptoms. |
Countries
Switzerland
Participant flow
Recruitment details
Participants were recruited by calling for referrals from psychiatric hospitals, trauma counseling centers, psychiatrists and psychotherapists in the German-speaking part of Switzerland.
Pre-assignment details
Only active control participants from Stage 1 entered into open-label Stage 2 and only participants who received full dose in Stage1 or Stage 2 and did not respond with significant improvement were offered the opportunity to partake in open-label Stage 3.
Participants by arm
| Arm | Count |
|---|---|
| Full Dose MDMA-assisted Therapy (125 mg) Three 8-hour sessions of MDMA-assisted therapy with 125 mg of MDMA, followed by a supplemental dose of 62.5 mg MDMA
3,4-methylenedioxymethamphetamine (125 mg): Participants will receive an initial dose of 125 mg MDMA orally and, if investigator and participant deem appropriate, 2.5 hours later they will receive 62.5 mg MDMA orally.
Therapy: Non-directive therapy performed by a team of two co-therapists | 8 |
| Active Placebo MDMA-assisted Therapy (25 mg) Three 8-hour sessions of MDMA-assisted therapy with 25 mg of MDMA, followed by a supplemental dose of 12.5 mg MDMA
3,4-methyelendioxymethamphetamine (25 mg): Participants will receive a 25 mg MDMA orally, and if investigator and participant agree, 2.5 hours later they will receive 12.5 mg MDMA orally.
Therapy: Non-directive therapy performed by a team of two co-therapists | 4 |
| Total | 12 |
Baseline characteristics
| Characteristic | Full Dose MDMA-assisted Therapy (125 mg) | Active Placebo MDMA-assisted Therapy (25 mg) | Total |
|---|---|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 12.8 | 40.0 years STANDARD_DEVIATION 6.2 | 41.4 years STANDARD_DEVIATION 11.2 |
| Country of origin France | 1 Participants | 0 Participants | 1 Participants |
| Country of origin Switzerland | 7 Participants | 4 Participants | 11 Participants |
| Duration of prior therapy | 39.9 months STANDARD_DEVIATION 73.3 | 123 months STANDARD_DEVIATION 60.6 | 85.8 months STANDARD_DEVIATION 71.4 |
| Duration of PTSD | 16.4 years STANDARD_DEVIATION 10.9 | 22.3 years STANDARD_DEVIATION 12.1 | 18.3 years STANDARD_DEVIATION 12 |
| On medication for PTSD at enrollment No | 4 Participants | 2 Participants | 6 Participants |
| On medication for PTSD at enrollment Yes | 4 Participants | 2 Participants | 6 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
| Work status Fit for limited employment | 2 Participants | 1 Participants | 3 Participants |
| Work status On disability | 4 Participants | 1 Participants | 5 Participants |
| Work status Retired | 1 Participants | 0 Participants | 1 Participants |
| Work status Working full-time | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 5 | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 8 / 9 | 3 / 5 | 2 / 4 | 1 / 3 |
| serious Total, serious adverse events | 2 / 9 | 0 / 5 | 0 / 4 | 0 / 3 |
Outcome results
Primary
Change From Baseline to Primary Endpoint in Clinician Administered PTSD Scale for DSM-IV (CAPS-IV)
The CAPS-IV is a structured clinical interview designed to assess the symptoms and severity of PTSD. The CAPS-IV provides a means to evaluate the frequency and intensity dimensions of each symptom, the impact of symptoms on the patient's social and occupational functioning, the overall severity of the symptom complex, global improvement since baseline, and the validity of the ratings obtained. Total severity scores range from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.
Time frame: Less than 4 weeks before first experimental session (Baseline) to 3 weeks post 3rd experimental session (Primary Endpoint)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Dose MDMA-assisted Therapy (125 mg) | Change From Baseline to Primary Endpoint in Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) | -15.6 score on a scale | Standard Deviation 18.1 |
| Active Placebo MDMA-assisted Therapy (25 mg) | Change From Baseline to Primary Endpoint in Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) | 3.3 score on a scale | Standard Deviation 15.3 |
Secondary
Change From Baseline to Primary Endpoint in Posttraumatic Stress Diagnostic Scale (PDS)
The Posstraumatic Stress Diagnostic Scale (PSD) is a 49-item self-report instrument to aid in the diagnosis of PTSD. Questions are asked about symptoms experienced and participants respond on a scale from 0 (not at all or only one time) to 3 (5 or more times a week/almost always). Items are summed to create a total score that ranges from 0 to 51, with higher scores indicating more PTSD symptoms.
Time frame: Less than 4 weeks before first experimental session (Baseline) to 3 weeks post 3rd experimental session (Primary Endpoint)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Dose MDMA-assisted Therapy (125 mg) | Change From Baseline to Primary Endpoint in Posttraumatic Stress Diagnostic Scale (PDS) | -8.6 score on a scale | Standard Deviation 13 |
| Active Placebo MDMA-assisted Therapy (25 mg) | Change From Baseline to Primary Endpoint in Posttraumatic Stress Diagnostic Scale (PDS) | 7.3 score on a scale | Standard Deviation 6.2 |