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This pilot study was terminated early by sponsor due to insufficient rate of accrual.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo with therapy | Placebo Comparator | Participants will receive placebo with therapy during each of two experimental sessions. |
|
| MDMA-assisted therapy | Experimental | Participants will receive MDMA (initial dose of 125 mg midomafetamine HCl followed by a supplemental dose of 62.5 mg midomafetamine HCl) with therapy during each of two experimental sessions. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo with therapy administered in two blinded experimental sessions. Participants in this group in Stage 1 may take part in Stage 2. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ingrid Pacey, MBBS FRCP[C] | University of Victoria | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Offices of Dr. Ingrid Pacey MBBS FRCP[C] | Vancouver | British Columbia | V6R 1N6 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32500209 | Derived | Jerome L, Feduccia AA, Wang JB, Hamilton S, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl). 2020 Aug;237(8):2485-2497. doi: 10.1007/s00213-020-05548-2. Epub 2020 Jun 4. | |
| 31572236 |
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Participants were recruited through printed ads, internet ads, referrals from other psychiatrists, psychotherapists or physicians, and through word of mouth.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo With Therapy | Participants will receive placebo with therapy during each of two experimental sessions. |
| FG001 | MDMA-assisted Therapy | Participants will receive full-dose (125 mg) MDMA with therapy during each of two experimental sessions. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stage 1 |
| |||||||||||||
| Stage 2 Open-label Crossover |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo With Therapy | Participants will receive placebo with therapy during each of two blinded experimental sessions. |
| BG001 | MDMA-assisted Therapy | Participants will receive MDMA-assisted therapy during each of two blinded experimental sessions. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
|
All AEs from baseline to the end of Stage 2 (approximately 10 months)
Treatment group is the Stage 1 randomized treatment assignment (i.e. Results for "Placebo with Therapy" participants in Stage 2 reflect results following open-label crossover to complete 3 MDMA-assisted therapy sessions).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo With Therapy (Stage 1) | Participants will receive placebo during each of two experimental sessions. Placebo: Placebo administered in two experimental sessions; may take part in Stage 2 upon learning condition assignment Psychotherapy: Psychotherapy before and after experimental sessions |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Lykos Therapeutics | 877-627-7722 | trialdata@lykospbc.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 20, 2014 | Sep 11, 2024 | Prot_003.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 31, 2016 | Jun 9, 2021 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 20, 2014 | Jun 14, 2022 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D013313 | Stress Disorders, Post-Traumatic |
| ID | Term |
|---|---|
| D040921 | Stress Disorders, Traumatic |
| D000068099 | Trauma and Stressor Related Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D018817 | N-Methyl-3,4-methylenedioxyamphetamine |
| D011613 | Psychotherapy |
| ID | Term |
|---|---|
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 |
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|
| Midomafetamine HCl | Drug | Participants will receive MDMA-assisted therapy during two blinded experimental sessions. After unblinding, may receive a third session of open-label MDMA-assisted therapy. |
|
|
| Psychotherapy | Behavioral | Psychotherapy before and after experimental sessions. |
|
| Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
| 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. | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
| 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. | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
| 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. | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
| 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. | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
| 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. | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
| Feduccia AA, Jerome L, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. Front Psychiatry. 2019 Sep 12;10:650. doi: 10.3389/fpsyt.2019.00650. eCollection 2019. |
| 31065731 | Derived | Mithoefer MC, Feduccia AA, Jerome L, Mithoefer A, Wagner M, Walsh Z, Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 2019 Sep;236(9):2735-2745. doi: 10.1007/s00213-019-05249-5. Epub 2019 May 7. |
| NOT COMPLETED |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
Participants will receive placebo with therapy during each of two experimental sessions. |
| OG001 | MDMA-assisted Therapy | Participants will receive full-dose (125 mg) MDMA with therapy during each of two experimental sessions. |
|
|
| 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. | One participant in the MDMA group did not provide PDS data at Primary Endpoint so is excluded from this analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
|
|
|
| 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
|
|
|
| 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
|
|
|
| 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
|
|
|
| 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. | DES-II data was not collected in one MDMA participant at the endpoint assessment so is excluded from this analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
|
|
|
| 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. | PTGI data was not collected in one MDMA participant at the endpoint assessment so is excluded from this analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Primary Endpoint (Primary Endpoint was approximately 18 weeks after Baseline and 1 month after the 2nd experimental session) |
|
|
|
| 0 |
| 2 |
| 0 |
| 2 |
| 2 |
| 2 |
| EG001 | MDMA-assisted Therapy (Stage 1) | Participants will receive full-dose MDMA during each of two experimental sessions. 3,4-methylenedioxymethamphetamine: Participants receive full-dose MDMA during two experimental sessions; after learning their condition assignment, participants will receive a third full-dose session. Psychotherapy: Psychotherapy before and after experimental sessions | 0 | 4 | 0 | 4 | 4 | 4 |
| EG002 | Placebo With Therapy (Stage 2) | Stage 1 placebo participants will receive full-dose MDMA during each of two experimental sessions. 3,4-methylenedioxymethamphetamine: Participants receive full-dose MDMA during two experimental sessions; after learning their condition assignment, participants will receive a third full-dose session. Psychotherapy: Psychotherapy before and after experimental sessions | 0 | 2 | 0 | 2 | 2 | 2 |
| EG003 | SRRs: Placebo With Therapy | Spontaneously reported reactions (SRRs) on blinded experimental session days and 7 days after. | 0 | 2 | 0 | 2 | 2 | 2 |
| EG004 | SRRs: MDMA-assisted Therapy | Spontaneously reported reactions (SRRs) on blinded experimental session days and 7 days after. | 0 | 4 | 0 | 4 | 4 | 4 |
| Fatigue | General disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Muscle tightness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | Systematic Assessment |
|
| Depressed Mood | Psychiatric disorders | Systematic Assessment |
|
| Emotional distress | Psychiatric disorders | Systematic Assessment |
|
| Bruxism | Psychiatric disorders | Systematic Assessment |
|
| Dissociation | Psychiatric disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
| Intentional self-injury | Psychiatric disorders | Systematic Assessment |
|
| Restlessness | Psychiatric disorders | Systematic Assessment |
|
| Concussion | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Diarrhea | General disorders | Systematic Assessment |
|
| Difficulty Concentrating | General disorders | Systematic Assessment |
|
| Dizziness | General disorders | Systematic Assessment |
|
| Dry mouth | General disorders | Systematic Assessment |
|
| Impaired Gait/Balance | General disorders | Systematic Assessment |
|
| Increased Irritability | General disorders | Systematic Assessment |
|
| Jaw Clenching, Tight Jaw | General disorders | Systematic Assessment |
|
| Lack of Appetite | General disorders | Systematic Assessment |
|
| Low mood | General disorders | Systematic Assessment |
|
| Muscle Tension | General disorders | Systematic Assessment |
|
| Need More Sleep | General disorders | Systematic Assessment |
|
| Perspiration | General disorders | Systematic Assessment |
|
| Ruminations | General disorders | Systematic Assessment |
|
| Sensitivity to Cold | General disorders | Systematic Assessment |
|
| Weakness | General disorders | Systematic Assessment |
|
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| Organic Chemicals |
| D004191 | Behavioral Disciplines and Activities |