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

Phase 1

Completed

• Conditions: Posttraumatic Stress Disorder
• Interventions: Drug: MDMA; Behavioral: CBCT; Behavioral: Therapy

• Registration Number: NCT02876172
• Lead Sponsor: Lykos Therapeutics

Brief Summary

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.

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 Timeline

• Study Start: 2016-07-03
• Study First Submitted: 2016-08-16
• Study First Submitted QC: 2016-08-18
• Study First Posted: 2016-08-23
• Primary Completion: 2017-12-16
• Study Completion: 2018-05-29
• Disposition First Submitted: 2019-06-26
• Disposition First Submitted QC: 2019-06-26
• Disposition First Posted: 2019-07-02
• Results First Submitted: 2021-06-25
• Results First Submitted QC: 2021-07-15
• Results First Posted: 2021-07-19
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-22
• Last Update Posted: 2024-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MDMA and CBCT	MDMA	Cognitive-behavioral conjoint therapy and 2 sessions of MDMA-assisted therapy.
MDMA and CBCT	CBCT	Cognitive-behavioral conjoint therapy and 2 sessions of MDMA-assisted therapy.
MDMA and CBCT	Therapy	Cognitive-behavioral conjoint therapy and 2 sessions of MDMA-assisted therapy.

Primary Outcome Measures

Name	Time	Method
Baseline Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score	Baseline (screening)	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 Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Severity Score	Primary Endpoint (Visit 16, approximately 2 months later)	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.

Secondary Outcome Measures

Name	Time	Method
Baseline Partner Couples Satisfaction Index (CSI)	Baseline (screening)	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 Emotion Regulation Questionnaire (ERQ) Suppression Subscale	Primary Endpoint (Visit 16, approximately 2 months later)	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 Pittsburgh Sleep Quality Index (PSQI)	Primary Endpoint (Visit 16, approximately 2 months later)	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 Pittsburgh Sleep Quality Index (PSQI)	Baseline (screening)	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 Patient Beck Depression Inventory-II (BDI-II)	Baseline (screening)	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 Patient Beck Depression Inventory-II (BDI-II)	Primary Endpoint (Visit 16, approximately 2 months later)	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 Patient Couples Satisfaction Index (CSI)	Baseline (screening)	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 Patient Couples Satisfaction Index (CSI)	Primary Endpoint (Visit 16, approximately 2 months later)	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 Partner Couples Satisfaction Index (CSI)	Primary Endpoint (Visit 16, approximately 2 months later)	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 Trauma and Attachment Beliefs Scale (TABS)	Baseline (screening)	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 Patient PTSD Checklist-5 (PCL-5)	Baseline (screening)	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 Patient PTSD Checklist-5 (PCL-5)	Primary Endpoint (Visit 16, approximately 2 months later)	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 Partner-rated PTSD Checklist-5 (PCL-5)	Baseline (screening)	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 Partner-rated PTSD Checklist-5 (PCL-5)	Primary Endpoint (Visit 16, approximately 2 months later)	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 Trauma and Attachment Beliefs Scale (TABS)	Primary Endpoint (Visit 16, approximately 2 months later)	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 Emotion Regulation Questionnaire (ERQ) Reappraisal Subscale	Baseline (screening)	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 Emotion Regulation Questionnaire (ERQ) Reappraisal Subscale	Primary Endpoint (Visit 16, approximately 2 months later)	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 Emotion Regulation Questionnaire (ERQ) Suppression Subscale	Baseline (screening)	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.

Trial Locations

Locations (1)

Offices of Michael Mithoefer MD; 🇺🇸 Mount Pleasant, South Carolina, United States