MDMA-assisted and Cognitive-Behavioral Conjoint Therapy (CBCT) in Dyads With One Member With Chronic PTSD
| Status: | Completed |
|---|---|
| Conditions: | Psychiatric, Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 7/15/2018 |
| Start Date: | October 2016 |
| End Date: | July 2018 |
Phase 1/2 Open-Label Treatment Development Study of MDMA-Assisted Cognitive-Behavioral Conjoint Therapy (CBCT) in Dyads in Which 1 Member Has Chronic Posttraumatic Stress Disorder (PTSD)
This small study will look at the safety and estimate the strength of effect (effect size) of
a combination of Cognitive Behavioral Conjoint Therapy (CBCT) and
3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in ten pairs of people, one
with and one without PTSD. The pairs can be spouses or romantic partners, siblings or other
relatives or close friends. The study will measure PTSD symptoms, as well as symptoms of
depression, sleep quality and relationship satisfaction and functioning before and after a
one-month course of CBCT that includes two MDMA+CBCT visits. CBCT psychotherapy is designed
to treat PTSD and relationship problems in pairs in a close relationship, and MDMA-assisted
psychotherapy uses the experimental drug MDMA to enhance and strengthen psychotherapy. There
is evidence that each of these treatments, on its own, can help people with PTSD. The study
will also measure personality and how each member of a pair thinks about and behaves in
relationships and expresses emotions before and after having MDMA+CBCT. Pairs will have two
day-long sessions scheduled two weeks apart. During the first MDMA+CBCT session, both members
of the pair will receive 75 mg MDMA with the option of receiving a second dose of 37.5
approximately an hour and a half later. During the second session of MDMA+CBCT, subjects may
receive either 100 or 75 mg, with the decision concerning dose made by the researchers after
discussion with the subjects. An optional dose half the size of the initial dose will be
offered approximately an hour and a half later. Following informed consent and screening
there will be one enrollment visit over videoconference. Before the first MDMA+CBCT session,
there will be an introductory session including 3 segments of CBCT psychotherapy on the day
before the first MDMA session. The introductory session and the CBCT sessions will be done in
person at the study site. During each MDMA+CBCT sessions, two therapists will work with with
the pair. Blood pressure, heart rate and body temperature will be measured periodically
during each MDMA+CBCT session. The pair will stay at the study site overnight with a night
attendant on duty, and they will have an integrative psychotherapy session on the morning
after the MDMA+CBCT session. Each member of the pair will be contacted by the researchers for
a week after each MDMA+CBCT session. The pair will have CBCT and integrative sessions over
videoconferencing twice a week for two weeks following the on-site integrative session. One
month after the second MDMA+CBCT session, both participants will have an evaluation and
testing visit over videoconference and will complete measures of PTSD symptoms, sleep
quality, perceived growth related to experiencing a trauma, symptoms of depression, and how
people think and feel about emotions and their relationships. The member of the pair with
PTSD will also undergo an interview measure of PTSD symptoms. The pair will complete measures
and questionnaires three and six months after the second MDMA+CBCT session. The study is open
label, meaning the researchers and subjects will be aware of the doses of MDMA used in the
study. The study will test and compare changes in symptoms and relationship issues before and
after the course of psychotherapy.
a combination of Cognitive Behavioral Conjoint Therapy (CBCT) and
3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in ten pairs of people, one
with and one without PTSD. The pairs can be spouses or romantic partners, siblings or other
relatives or close friends. The study will measure PTSD symptoms, as well as symptoms of
depression, sleep quality and relationship satisfaction and functioning before and after a
one-month course of CBCT that includes two MDMA+CBCT visits. CBCT psychotherapy is designed
to treat PTSD and relationship problems in pairs in a close relationship, and MDMA-assisted
psychotherapy uses the experimental drug MDMA to enhance and strengthen psychotherapy. There
is evidence that each of these treatments, on its own, can help people with PTSD. The study
will also measure personality and how each member of a pair thinks about and behaves in
relationships and expresses emotions before and after having MDMA+CBCT. Pairs will have two
day-long sessions scheduled two weeks apart. During the first MDMA+CBCT session, both members
of the pair will receive 75 mg MDMA with the option of receiving a second dose of 37.5
approximately an hour and a half later. During the second session of MDMA+CBCT, subjects may
receive either 100 or 75 mg, with the decision concerning dose made by the researchers after
discussion with the subjects. An optional dose half the size of the initial dose will be
offered approximately an hour and a half later. Following informed consent and screening
there will be one enrollment visit over videoconference. Before the first MDMA+CBCT session,
there will be an introductory session including 3 segments of CBCT psychotherapy on the day
before the first MDMA session. The introductory session and the CBCT sessions will be done in
person at the study site. During each MDMA+CBCT sessions, two therapists will work with with
the pair. Blood pressure, heart rate and body temperature will be measured periodically
during each MDMA+CBCT session. The pair will stay at the study site overnight with a night
attendant on duty, and they will have an integrative psychotherapy session on the morning
after the MDMA+CBCT session. Each member of the pair will be contacted by the researchers for
a week after each MDMA+CBCT session. The pair will have CBCT and integrative sessions over
videoconferencing twice a week for two weeks following the on-site integrative session. One
month after the second MDMA+CBCT session, both participants will have an evaluation and
testing visit over videoconference and will complete measures of PTSD symptoms, sleep
quality, perceived growth related to experiencing a trauma, symptoms of depression, and how
people think and feel about emotions and their relationships. The member of the pair with
PTSD will also undergo an interview measure of PTSD symptoms. The pair will complete measures
and questionnaires three and six months after the second MDMA+CBCT session. The study is open
label, meaning the researchers and subjects will be aware of the doses of MDMA used in the
study. The study will test and compare changes in symptoms and relationship issues before and
after the course of psychotherapy.
PTSD is a debilitating psychiatric disorder arising after a traumatic life event. The
condition is a public health issue. There are recognized psychotherapeutic and pharmacologic
treatments for PTSD, but a wider array of treatments is needed. Methylenedioxymethamphetamine
(MDMA) has shown promise in Phase 2 research studies as a psychotherapeutic adjunct for
people with PTSD. 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 engaging an individual with PTSD and a "concerned significant other" in
addressing PTSD symptoms, and relationship issues together. During the course of CBCT, pairs
are provided with information about PTSD and the therapy rationale, address relationship
issues and a key PTSD symptom and consider the meaning of the traumatic event. MDMA-assisted
psychotherapy is a manualized treatment developed to use the effects of MDMA to enhance and
strengthen the therapeutic process, and it includes preparatory and integrative sessions that
occur prior to and after up to three sessions of MDMA-assisted psychotherapy.
This study will combine methods described in the Treatment Manual for conducting
MDMA-assisted psychotherapy with methods from the CBCT for PTSD manual. A combined treatment
of MDMA-assisted psychotherapy and CBCT may be especially useful for treating PTSD because
MDMA can attenuate the fear arising in response to perceived threat to one's emotional
integrity and decrease defensiveness without blocking access to memories or preventing a deep
and genuine experience of emotion. Elimination of these conditioned fear responses can lead
to more open and comfortable communication about past traumatic events and greater access to
information about them. Participants are expected to be able to experience and express fear,
anger, and grief, and to be able to engage in the CBCT sessions with less likelihood of
feeling overwhelmed by these emotions. As a result, MDMA-assisted psychotherapy with CBCT may
enable the participants to develop a wider behavioral and emotional repertoire with which to
communicate with each other and respond to anxiogenic stimuli.
This is a Phase 1/2 open-label study in 10 dyads (pairs) that include a participant who has
been diagnosed with PTSD for at least 6 months (PTSD+ participant) and a concerned
significant other participant (i.e., intimate or non-intimate person) who does not have a
current diagnosis of PTSD (CSO participant). The overall objective of this study is to
explore the safety and estimate the effect size of MDMA-assisted psychotherapy in conjunction
with CBCT (MDMA+CBCT) on PTSD symptoms in participants with PTSD and, to examine relationship
functioning in both participants. Dyads in this study will be enrolled in a course of CBCT
that will also include two sessions of MDMA-assisted psychotherapy. Eligible and enrolled
participants will undergo a 1-month course of psychotherapy as a dyad that includes CBCT for
PTSD integrated with MDMA-assisted psychotherapy.
Prior to the first session with MDMA and CBCT, participants will undergo an introductory
psychotherapy session via telemedicine (videoconference) followed by a five-hour CBCT visit
at the study site. After each MDMA+CBCT session, the pair will have integrative sessions that
include an on-site integrative session on the day following MDMA+CBCT and further integrative
and CBCT sessions conducted via videoconference.
During the first experimental (MDMA+CBCT) session, both members of the pair will receive 75
mg MDMA with the option of receiving a second dose of 37.5 approximately an hour and a half
later. During the second session, subjects may receive either 100 or 75 mg, with the decision
concerning dose made by the researchers. An optional dose half the size of the initial dose
may be offered approximately an hour and a half later. The doses used in this study have been
investigated by researchers conducting trials in healthy human volunteers and people with
PTSD. Vital signs (blood pressure, heart rate and body temperature) will be periodically
measured during the session, and the pair will complete simple measures of state
interpersonal closeness and degree of distress. They will have an overnight stay at the study
site, followed by the first post-session integrative session on the day after the
experimental session. The researchers will contact the PTSD+ and CSO daily for a week after
each MDMA+CBCT session, with contact possible through telephone or teleconference line.
Integrative sessions will occur over teleconference (telemedicine) line. Integrative
psychotherapy held over videoconference falls after the on-site integrative session.
Thirteen days after the first experimental session, the dyad meet with the investigators at
the study site to complete measures of PTSD symptoms, symptoms of other conditions, emotion
perception and regulation, sleep quality, facets of interpersonal relationships and
psychological function. The course of combined CBCT and MDMA-assisted psychotherapy will
continue until approximately two and a half weeks after the second MDMA+CBCT session, when
the primary endpoint assessment will occur. The dyad will be assessed at the three month and
six month follow up visits.
Dyads will participate in an introductory session, CBCT sessions, two day-long MDMA+CBCT
sessions, and five integrative sessions after each MDMA+ CBCT session. PTSD symptoms, growth
from trauma experience, sleep quality, symptoms of depression, other psychological symptoms
or difficulties, emotion regulation, emotion perception, relationship factors, and facets of
life function will be measured two weeks after the first MDMA-assisted session and five
weeks, three months and six months after the second and final MDMA-assisted session.
Assessment five weeks after the second experimental (MDMA-assisted) session will be the study
primary endpoint. The Clinician Administered PTSD Scale - 5 (CAPS-5) will be the primary
outcome measure, with drops in CAPS-5 Global Severity score expected from baseline to primary
endpoint. There will be follow up assessments three and six months after the second MDMA+CBCT
session. Safety data collected will include vital signs during each MDMA+CBCT session,
suicidal ideation and behavior assessed with the Columbia Suicide Severity Rating Scale
(C-SSRS). Adverse events will be collected throughout the course of the study.
condition is a public health issue. There are recognized psychotherapeutic and pharmacologic
treatments for PTSD, but a wider array of treatments is needed. Methylenedioxymethamphetamine
(MDMA) has shown promise in Phase 2 research studies as a psychotherapeutic adjunct for
people with PTSD. 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 engaging an individual with PTSD and a "concerned significant other" in
addressing PTSD symptoms, and relationship issues together. During the course of CBCT, pairs
are provided with information about PTSD and the therapy rationale, address relationship
issues and a key PTSD symptom and consider the meaning of the traumatic event. MDMA-assisted
psychotherapy is a manualized treatment developed to use the effects of MDMA to enhance and
strengthen the therapeutic process, and it includes preparatory and integrative sessions that
occur prior to and after up to three sessions of MDMA-assisted psychotherapy.
This study will combine methods described in the Treatment Manual for conducting
MDMA-assisted psychotherapy with methods from the CBCT for PTSD manual. A combined treatment
of MDMA-assisted psychotherapy and CBCT may be especially useful for treating PTSD because
MDMA can attenuate the fear arising in response to perceived threat to one's emotional
integrity and decrease defensiveness without blocking access to memories or preventing a deep
and genuine experience of emotion. Elimination of these conditioned fear responses can lead
to more open and comfortable communication about past traumatic events and greater access to
information about them. Participants are expected to be able to experience and express fear,
anger, and grief, and to be able to engage in the CBCT sessions with less likelihood of
feeling overwhelmed by these emotions. As a result, MDMA-assisted psychotherapy with CBCT may
enable the participants to develop a wider behavioral and emotional repertoire with which to
communicate with each other and respond to anxiogenic stimuli.
This is a Phase 1/2 open-label study in 10 dyads (pairs) that include a participant who has
been diagnosed with PTSD for at least 6 months (PTSD+ participant) and a concerned
significant other participant (i.e., intimate or non-intimate person) who does not have a
current diagnosis of PTSD (CSO participant). The overall objective of this study is to
explore the safety and estimate the effect size of MDMA-assisted psychotherapy in conjunction
with CBCT (MDMA+CBCT) on PTSD symptoms in participants with PTSD and, to examine relationship
functioning in both participants. Dyads in this study will be enrolled in a course of CBCT
that will also include two sessions of MDMA-assisted psychotherapy. Eligible and enrolled
participants will undergo a 1-month course of psychotherapy as a dyad that includes CBCT for
PTSD integrated with MDMA-assisted psychotherapy.
Prior to the first session with MDMA and CBCT, participants will undergo an introductory
psychotherapy session via telemedicine (videoconference) followed by a five-hour CBCT visit
at the study site. After each MDMA+CBCT session, the pair will have integrative sessions that
include an on-site integrative session on the day following MDMA+CBCT and further integrative
and CBCT sessions conducted via videoconference.
During the first experimental (MDMA+CBCT) session, both members of the pair will receive 75
mg MDMA with the option of receiving a second dose of 37.5 approximately an hour and a half
later. During the second session, subjects may receive either 100 or 75 mg, with the decision
concerning dose made by the researchers. An optional dose half the size of the initial dose
may be offered approximately an hour and a half later. The doses used in this study have been
investigated by researchers conducting trials in healthy human volunteers and people with
PTSD. Vital signs (blood pressure, heart rate and body temperature) will be periodically
measured during the session, and the pair will complete simple measures of state
interpersonal closeness and degree of distress. They will have an overnight stay at the study
site, followed by the first post-session integrative session on the day after the
experimental session. The researchers will contact the PTSD+ and CSO daily for a week after
each MDMA+CBCT session, with contact possible through telephone or teleconference line.
Integrative sessions will occur over teleconference (telemedicine) line. Integrative
psychotherapy held over videoconference falls after the on-site integrative session.
Thirteen days after the first experimental session, the dyad meet with the investigators at
the study site to complete measures of PTSD symptoms, symptoms of other conditions, emotion
perception and regulation, sleep quality, facets of interpersonal relationships and
psychological function. The course of combined CBCT and MDMA-assisted psychotherapy will
continue until approximately two and a half weeks after the second MDMA+CBCT session, when
the primary endpoint assessment will occur. The dyad will be assessed at the three month and
six month follow up visits.
Dyads will participate in an introductory session, CBCT sessions, two day-long MDMA+CBCT
sessions, and five integrative sessions after each MDMA+ CBCT session. PTSD symptoms, growth
from trauma experience, sleep quality, symptoms of depression, other psychological symptoms
or difficulties, emotion regulation, emotion perception, relationship factors, and facets of
life function will be measured two weeks after the first MDMA-assisted session and five
weeks, three months and six months after the second and final MDMA-assisted session.
Assessment five weeks after the second experimental (MDMA-assisted) session will be the study
primary endpoint. The Clinician Administered PTSD Scale - 5 (CAPS-5) will be the primary
outcome measure, with drops in CAPS-5 Global Severity score expected from baseline to primary
endpoint. There will be follow up assessments three and six months after the second MDMA+CBCT
session. Safety data collected will include vital signs during each MDMA+CBCT session,
suicidal ideation and behavior assessed with the Columbia Suicide Severity Rating Scale
(C-SSRS). Adverse events will be collected throughout the course of the study.
Inclusion Criteria:
- All inclusion criteria for the PTSD and 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
We found this trial at
1
site
Mount Pleasant, South Carolina 29464
Principal Investigator: Michael Mithoefer, MD
Phone: 843-849-6899
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