Posttraumatic Stress Disorder
Conditions
Keywords
PTSD, MDMA, therapy, Posttraumatic stress disorder, Israel
Brief summary
The goal of this clinical trial is to learn if MDMA-assisted therapy can treat PTSD in participants with PTSD. Researchers will compare two sessions of MDMA-assisted therapy with two sessions of low dose (active placebo) MDMA-assisted therapy to determine if MDMA-assisted therapy is safe and works to treat PTSD symptoms. Participants will be randomly assigned to receive either the full dose of MDMA or low active placebo dose of MDMA during each of two experimental sessions. PTSD symptoms will be measured throughout the study.
Detailed description
This study will examine whether two six to eight-hour long sessions of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy scheduled two to four weeks apart are safe, and whether combining a fully therapeutic dose of MDMA with psychotherapy, compared with a low (active placebo) dose of MDMA, will reduce PTSD symptoms, with symptoms measured four times, once at baseline and again 2, 6, and 12 months after the second experimental session. People who received the active placebo dose of MDMA can then take part in an open label study continuation, with the participant receiving a fully active dose of MDMA on two more six to eight hour-long psychotherapy sessions. Open-label means that the participants and the researchers know that the participant will receive the fully active dose of MDMA. People who take part in the open label study continuation have their PTSD symptoms checked six and 12 months after the second open label MDMA-assisted session. This study will look at MDMA-assisted therapy in 12 individuals aged 18 years or older, with PTSD symptoms not improving after trying at least one treatment. At least two-thirds of participants will have diagnosed PTSD arising from war or terrorism-related trauma. Eight of 12 participants will be assigned to receive the full dose of MDMA, and four will be assigned to receive a low or active placebo dose of MDMA during each of two experimental sessions. The fully active dose consists of an initial dose of 125 mg MDMA HCl and a supplemental dose of 62.5 mg given 2 to 2.5 hours later. The active placebo dose consists of an initial dose of 25 mg MDMA HCl and a supplemental dose of 12.5 mg. The study will will include two sixty minute long introductory therapy sessions, two active placebo or fully active dose MDMA-assisted therapy sessions, a sixty to ninety minute long therapy session 24 hours after each experimental session, and one to two hour-long therapy sessions occurring weekly between the first and second experimental session, and between the second experimental session and the end of the study.
Interventions
DRUGFull Dose Midomafetamine HCl
Participants will receive an initial dose of 125 mg midomafetamine HCl orally followed 2.5 hours later by 62.5 mg midomafetamine HCl orally during the course of a day-long therapy session.
DRUGLow Dose Midomafetamine HCl
Participants will receive an initial dose of 25 mg midomafetamine HCl orally followed 2.5 hours later by a supplemental dose of 12.5 mg midomafetamine HCl orally during the course of each of two day-long therapy sessions.
Sponsors
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
* Diagnosis of Posttraumatic stress disorder still remaining after at least one treatment, with treatment including psychotherapy or pharmacotherapy. At least two-thirds of participants will have PTSD as a result of war and terrorism * May meet criteria for a mood disorder. * Must be at least 18 years old. * Must be able to stop taking psychiatric medication from the start of the study until the two-month follow-up. * May continue seeing an outside therapist during the study, but cannot increase the length or frequency of treatments. * Must be able to follow all the rules and instructions relating to the experimental session, including restrictions on food and substance (alcohol and drug) consumption * Must be willing to stay overnight in the clinic 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. * If a woman of childbearing potential, must have a negative pregnancy test and must agree to use an effective form of birth control. * Must be able to speak and read Hebrew.
Exclusion criteria
* Cannot have history of or be diagnosed with psychotic disorder or bipolar affective disorder - 1. * Cannot be diagnosed with dissociative identity disorder, an eating disorder with active purging, or borderline personality disorder. * Cannot have 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). * Cannot have uncontrolled hypertension, peripheral vascular disease, hepatic disease (with or without abnormal liver enzymes), or history of hyponatremia or hyperthermia. * Cannot weigh less than 50 or more than 105 kg. * Cannot have used Ecstasy more than five times during lifetime or in the past six months. * Cannot present a serious suicide risk or be likely to require hospitalization during the course of the study. * Cannot require ongoing concomitant therapy with a psychotropic drug. * Cannot meet DSM-IV criteria for substance abuse or dependence for any substance save caffeine or nicotine in the past 60 days. * Unable to give adequate consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 2-Month Follow-Up | Baseline to two months after second MDMA-assisted experimental session | The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. It contains symptom subscales, a CAPS-IV 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 Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 6-Month Follow-Up | Baseline to six months after second MDMA-assisted experimental session | The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. It contains symptom subscales, a CAPS-IV 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. |
| Change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 12-month Follow-up | Baseline to twelve months after second MDMA-assisted experimental session | The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. It contains symptom subscales, a CAPS-IV 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. |
Countries
Israel
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Full Dose (125 mg) Participants will receive an initial dose of 125 mg MDMNA followed 2.5 hours later by a supplemental dose of 62.5 mg MDMA during the course of two day-long psychotherapy sessions.
3,4-methylenedioxymethemphetmaine (MDMA\_: Participants will receive an initial dose of 125 mg MDMA orally followed 2.5 hours later by 62.5 mg MDMA orally during the course of a day-long psychotherapy session. | 3 |
| Active Comparator (25 mg) 25 and 12.5 mg MDMA
3,4-methylenedioxymethamphetamine: Participants will receive an initial dose of 25 mg MDMA orally followed 2.5 hours alter by a supplemental dose of 12.5 mg MDMA orally during the course of each of two day-long psychotherapy sessions. | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Active Comparator (25 mg) | Full Dose (125 mg) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Continuous | 39 Years | 45.6 Years | 43 Years |
| Region of Enrollment Israel | 2 participants | 3 participants | 5 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 2 / 3 | 2 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
Primary
Change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 2-Month Follow-Up
The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. It contains symptom subscales, a CAPS-IV 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 two months after second MDMA-assisted experimental session
Population: One Full Dose participant did not complete a CAPS-IV assessment at the 2-month endpoint and is accordingly not included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Dose (125 mg) MDMA-assisted Therapy | Change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 2-Month Follow-Up | -0.5 units on a scale | Standard Deviation 4.95 |
| Low Dose (25 mg) MDMA-assisted Therapy | Change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 2-Month Follow-Up | -7 units on a scale | Standard Deviation 18.38 |
Secondary
Change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 12-month Follow-up
The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. It contains symptom subscales, a CAPS-IV 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 twelve months after second MDMA-assisted experimental session
Population: This study was terminated after enrolling five subjects due to staff turnover and its effects on quality of data collection. Limited data were reported to the sponsor and its quality could not be assured. All available data are reported; 12 month follow-up data available in 2 Full Dose participants, no 12 month follow-up data available in Low Dose participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Dose (125 mg) MDMA-assisted Therapy | Change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 12-month Follow-up | -7.5 score on a scale | Standard Deviation 13.43 |
Secondary
Change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 6-Month Follow-Up
The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. It contains symptom subscales, a CAPS-IV 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 six months after second MDMA-assisted experimental session
Population: One Full Dose participant and one Low Dose participant did not complete a 6-month CAPS-IV assessment and are accordingly not included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Dose (125 mg) MDMA-assisted Therapy | Change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 6-Month Follow-Up | -0.5 score on a scale | Standard Deviation 6.36 |
| Low Dose (25 mg) MDMA-assisted Therapy | Change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) at 6-Month Follow-Up | 6 score on a scale | — |