MDMA-Assisted Cognitive-Behavioral Conjoint Therapy (CBCT) in Dyads in Which 1 Member Has Chronic PTSD

A Phase 1/2 Open-Label Treatment Development Study of Methylenedioxymethamphetamine (MDMA)-Assisted Cognitive-Behavioral Conjoint Therapy (CBCT) in Dyads in Which 1 Member Has Chronic Posttraumatic Stress Disorder (PTSD)

This Phase 1/2 open-label study will combine methods for conducting MDMA-assisted therapy with methods from the CBCT for PTSD in order to treat 10 participants with chronic PTSD and their partners (intimate or non-intimate significant other who does not have a current diagnosis of PTSD) in order to explore whether combined treatment is effective. Each therapy team will have one therapist trained and experienced in MDMA assisted psychotherapy and one therapist trained and experienced in CBCT. During the first experimental session, both participants will receive 75 mg of MDMA followed 1.5 to 2 hours later by an optional supplemental half-dose of 37.5 mg. During the second experimental session, an initial dose of either 100 or 75 mg of MDMA will be administered to both participants followed by an optional supplemental half-dose of either 50 mg or 37.5 mg. The primary objective of this study is to assess changes in PTSD symptoms from Baseline to Primary Endpoint in CAPS-5 total severity scores in PTSD participants.

Study Overview

• Status: Completed
• Conditions: Posttraumatic Stress Disorder
• Intervention / Treatment: Drug: MDMA; Behavioral: CBCT; Behavioral: Therapy

Detailed Description

PTSD is a stress-related psychiatric condition that may occur following a traumatic event such as war, disaster, sexual abuse, violence, terrorism, and accidents. PTSD negatively impacts a person's daily life, resulting in relationship difficulties, difficulty in finding and maintaining a job, reduced cognitive and psychosocial functioning, substance abuse, high-cost healthcare use, and increased depression and suicide risk.

3,4-methylenedioxymethamphetamine is a drug that releases serotonin, norepinephrine and dopamine in the brain and indirectly increases levels of the neurohormones oxytocin, arginine vasopressin and cortisol. In the context of psychotherapy, MDMA has been noted to reduce defenses and fear of emotional injury while enhancing communication and capacity for introspection.

Cognitive-Behavioral Conjoint Therapy (CBCT) for PTSD is a three-phase, 15-session, manualized treatment. This Phase 1/2 open-label study will combine methods for conducting MDMA-assisted therapy with methods from the CBCT for PTSD in order to treat 10 participants with chronic PTSD and their partners (intimate or non-intimate significant other who does not have a current diagnosis of PTSD) in order to explore whether combined treatment is effective. Each therapy team will have one therapist trained and experienced in MDMA assisted therapy and one therapist trained and experienced in CBCT. During the first experimental session, both participants will receive 75 mg of MDMA followed 1.5 to 2 hours later by an optional supplemental half-dose of 37.5 mg. During the second experimental session, an initial dose of either 100 or 75 mg of MDMA will be administered to both participants followed by an optional supplemental half-dose of either 50 mg or 37.5 mg. The primary objective of this study is to assess changes in PTSD symptoms from Baseline to Primary Endpoint in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity scores in PTSD participants.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Offices of Michael Mithoefer MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• All inclusion criteria for the PTSD and Concerned Significant Other (CSO) are identical except for first two items, marked below:
• PTSD+ participant: Meet DSM-5 criteria for current PTSD and satisfies PTSD criteria via CAPS
• CSO participant: Meet criteria for V62.89 Other Problem Related to Psychosocial Circumstances under Diagnostic and Statistical Manual 5 (DSM-5), as determined through clinical interview, for current psychosocial circumstances contributing to relationship distress with intimate or non-intimate partner
• Are at least 18 years old
• If in psychotherapy, willing and able to maintain that schedule without changing it
• Are willing to refrain from taking any psychiatric medications during the study period, with the exception of gabapentin when prescribed for pain control.
• Willing to remain overnight at the study site
• Are willing to be driven home the morning after the experimental sessions, after the integrative therapy session
• Are willing to commit to medication dosing, experimental sessions, follow-up sessions, to complete evaluation instruments and commit to be contacted for all necessary telephone contacts
• Are willing to remain overnight at the study site after each experimental session until after the integrative session occurring the next morning
• Must have a negative pregnancy test at study entry and prior to each experimental session if able to bear children, and must agree to use adequate birth control through 10 days after the last dose of MDMA.
• Must provide a contact (relative, spouse, close friend or other caregiver other than the CSO participant) who is willing and able to be reached by the Clinical Investigators in the event of a participant becoming suicidal.
• Must agree to inform the Clinical Investigators within 48 hours of any medical conditions and procedures
• Are proficient in speaking and reading English
• Agree to have all clinic visit and Integrative Sessions recorded to audio and video
• Agree to not participate in any other interventional clinical trials during the duration of this study

Exclusion Criteria:

• The following exclusions are identical for PTSD+ and CSO participants except for the following, marked below:
• CSO participant only: Have diagnosis of current PTSD not in remission
• Are pregnant or nursing, or are women of child bearing potential who are not practicing an effective means of birth control
• Have evidence or history of significant medical disorders
• Have hypertension
• Have liver disease; asymptomatic participants with Hepatitis C who have previously undergone evaluation and successful treatment is permitted.
• History of hyponatremia or hyperthermia
• Weigh less than 48 kg
• Are abusing illegal drugs
• Are not able to give adequate informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MDMA and CBCT; Cognitive-behavioral conjoint therapy and 2 sessions of MDMA-assisted therapy.

Drug: MDMA; Two sessions of MDMA-assisted therapy, one with an initial dose of 75 mg (and optional supplemental dose of 37.5 mg) and the second with 75 or 100 mg MDMA (with optional supplemental dose of either 37.5 mg or 50 mg respectively) given to the participant with PTSD and their significant other.; Other Names: 3,4-Methylenedioxymethamphetamine; midomafetamine; Behavioral: CBCT; A three-phase, 15-session, manualized treatment from the CBCT manual; Other Names: Cognitive behavioral conjoint therapy; Behavioral: Therapy; Non-directive therapy (from the Multidisciplinary Association for Psychedelic Studies MDMA-assisted therapy treatment manual)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score	The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. It contains symptom subscales, a CAPS-5 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 (screening)
Primary Endpoint Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score	The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. It contains symptom subscales, a CAPS-5 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.	Primary Endpoint (Visit 16, approximately 2 months later)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Pittsburgh Sleep Quality Index (PSQI)	Self-reported questionnaire that assesses sleep quality and disturbances. The index looks at subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The component scores yield a total score which ranges 0-21 with a higher score indicating worse sleep quality.	Baseline (screening)
Primary Endpoint Pittsburgh Sleep Quality Index (PSQI)	Self-reported questionnaire that assesses sleep quality and disturbances. The index looks at subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The component scores yield a total score which ranges 0-21 with a higher score indicating worse sleep quality.	Primary Endpoint (Visit 16, approximately 2 months later)
Baseline Patient Beck Depression Inventory-II (BDI-II)	BDI-II is a 21-item self reported instrument used to measure severity of depressive symptoms. The 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 (screening)
Primary Endpoint Patient Beck Depression Inventory-II (BDI-II)	BDI-II is a 21-item self reported instrument used to measure severity of depressive symptoms. The 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.	Primary Endpoint (Visit 16, approximately 2 months later)
Baseline Patient Couples Satisfaction Index (CSI)	The Couples Satisfaction Index (CSI) is a self-reported 32-item scale measuring one's satisfaction in a relationship. Questions discuss overall happiness in relationship, extent of agreement/ disagreement between partners, and feelings towards relationships and are scored on a likert scale from 0 to 5, with higher scores indicating higher satisfaction in the relationship. Scores range from 0 to 160.	Baseline (screening)
Primary Endpoint Patient Couples Satisfaction Index (CSI)	The Couples Satisfaction Index (CSI) is a self-reported 32-item scale measuring one's satisfaction in a relationship. Questions discuss overall happiness in relationship, extent of agreement/ disagreement between partners, and feelings towards relationships and are scored on a likert scale from 0 to 5, with higher scores indicating higher satisfaction in the relationship. Scores range from 0 to 160.	Primary Endpoint (Visit 16, approximately 2 months later)
Baseline Partner Couples Satisfaction Index (CSI)	The Couples Satisfaction Index (CSI) is a self-reported 32-item scale measuring one's satisfaction in a relationship. Questions discuss overall happiness in relationship, extent of agreement/ disagreement between partners, and feelings towards relationships and are scored on a likert scale from 0 to 5, with higher scores indicating higher satisfaction in the relationship. Scores range from 0 to 160.	Baseline (screening)
Primary Endpoint Partner Couples Satisfaction Index (CSI)	The Couples Satisfaction Index (CSI) is a self-reported 32-item scale measuring one's satisfaction in a relationship. Questions discuss overall happiness in relationship, extent of agreement/ disagreement between partners, and feelings towards relationships and are scored on a likert scale from 0 to 5, with higher scores indicating higher satisfaction in the relationship. Scores range from 0 to 160.	Primary Endpoint (Visit 16, approximately 2 months later)
Baseline Trauma and Attachment Beliefs Scale (TABS)	TABS is a 84-item self-report scale, which measures responses on a 1 to 6 scale (1 = "Disagree Strongly, 6 = Agree Strongly) the degree to which respondents believe the statements correspond with their own beliefs. The measures of these beliefs relate to self-safety, other-safety, self-trust, other-trust, self-esteem, other-esteem, self-intimacy, other-intimacy, self-control, and other control. A TABS total score is calculated by summing all of the items (range 84 to 504). Higher scores indicate greater disruption.	Baseline (screening)
Primary Endpoint Trauma and Attachment Beliefs Scale (TABS)	TABS is a 84-item self-report scale, which measures responses on a 1 to 6 scale (1 = "Disagree Strongly, 6 = Agree Strongly) the degree to which respondents believe the statements correspond with their own beliefs. The measures of these beliefs relate to self-safety, other-safety, self-trust, other-trust, self-esteem, other-esteem, self-intimacy, other-intimacy, self-control, and other control. A TABS total score is calculated by summing all of the items (range 84 to 504). Higher scores indicate greater disruption.	Primary Endpoint (Visit 16, approximately 2 months later)
Baseline Emotion Regulation Questionnaire (ERQ) Reappraisal Subscale	ERQ measures self-reported emotional regulation and includes 10 items to assess means of coping with emotions via regulating them through reappraisal or suppression. Items range from 1 (strongly disagree) to 7 (strongly agree). Six of the items are summed to create the reappraisal total score, with total scores ranging from 6 to 42. Higher scores indicate greater emotional reappraisal.	Baseline (screening)
Primary Endpoint Emotion Regulation Questionnaire (ERQ) Reappraisal Subscale	ERQ measures self-reported emotional regulation and includes 10 items to assess means of coping with emotions via regulating them through reappraisal or suppression. Items range from 1 (strongly disagree) to 7 (strongly agree). Six of the items are summed to create the reappraisal total score, with total scores ranging from 6 to 42. Higher scores indicate greater emotional reappraisal.	Primary Endpoint (Visit 16, approximately 2 months later)
Baseline Emotion Regulation Questionnaire (ERQ) Suppression Subscale	ERQ measures self-reported emotional regulation and includes 10 items to assess means of coping with emotions via regulating them through reappraisal or suppression. Items range from 1 (strongly disagree) to 7 (strongly agree). Four of the items are summed to create the suppression total score, with total scores ranging from 4 to 28. Higher scores indicate greater emotional suppression.	Baseline (screening)
Primary Endpoint Emotion Regulation Questionnaire (ERQ) Suppression Subscale	ERQ measures self-reported emotional regulation and includes 10 items to assess means of coping with emotions via regulating them through reappraisal or suppression. Items range from 1 (strongly disagree) to 7 (strongly agree). Four of the items are summed to create the suppression total score, with total scores ranging from 4 to 28. Higher scores indicate greater emotional suppression.	Primary Endpoint (Visit 16, approximately 2 months later)
Baseline Patient PTSD Checklist-5 (PCL-5)	The PTSD Checklist-5 (PCL-5) is a 20-item self-reported questionnaire that follows DSM-5 criteria to assess PTSD presence and severity. Item scores range from 0 (not at all) to 4 (extremely). A total symptom severity score is determined by summing all items (range 0 to 80). A higher score indicates greater PTSD symptom severity.	Baseline (screening)
Primary Endpoint Patient PTSD Checklist-5 (PCL-5)	The PTSD Checklist-5 (PCL-5) is a 20-item self-reported questionnaire that follows DSM-5 criteria to assess PTSD presence and severity. Item scores range from 0 (not at all) to 4 (extremely). A total symptom severity score is determined by summing all items (range 0 to 80). A higher score indicates greater PTSD symptom severity.	Primary Endpoint (Visit 16, approximately 2 months later)
Baseline Partner-rated PTSD Checklist-5 (PCL-5)	The PTSD Checklist-5 (PCL-5) is a 20-item self-reported questionnaire that follows DSM-5 criteria to assess PTSD presence and severity. Item scores range from 0 (not at all) to 4 (extremely). A total symptom severity score is determined by summing all items (range 0 to 80). A higher score indicates greater PTSD symptom severity.	Baseline (screening)
Primary Endpoint Partner-rated PTSD Checklist-5 (PCL-5)	The PTSD Checklist-5 (PCL-5) is a 20-item self-reported questionnaire that follows DSM-5 criteria to assess PTSD presence and severity. Item scores range from 0 (not at all) to 4 (extremely). A total symptom severity score is determined by summing all items (range 0 to 80). A higher score indicates greater PTSD symptom severity.	Primary Endpoint (Visit 16, approximately 2 months later)

Collaborators and Investigators

• Sponsor: Lykos Therapeutics
• Investigators: Principal Investigator: Michael C Mithoefer, MD, Multidisciplinary Association for Psychedelic Studies

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2016
• Primary Completion (Actual): December 16, 2017
• Study Completion (Actual): May 29, 2018

Study Registration Dates

• First Submitted: August 16, 2016
• First Submitted That Met QC Criteria: August 18, 2016
• First Posted (Estimated): August 23, 2016

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: PTSD; cognitive behavioral therapy; MDMA; dyad; therapy
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Hallucinogens; Adrenergic Uptake Inhibitors; N-Methyl-3,4-methylenedioxyamphetamine
• Other Study ID Numbers: MPVA-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We plan to share outcome measure data upon request
• IPD Sharing Time Frame: After study data lock
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP