MPATHY: MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder
Study Details
Study Description
Brief Summary
To explore the effectiveness of of MDMA-assisted prolonged exposure therapy in improving treatment outcomes for individuals with comorbid PTSD and alcohol use disorder in a double-blind randomised placebo-controlled trial.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
New strategies for the treatment of comorbid PTSD and alcohol dependence are urgently required. Recent evidence has shown strong support for trauma-focused integrated treatments (namely COPE), however only 49% demonstrate clinically significant improvements. MDMA may be a promising approach to improve response to COPE for this population. Emerging evidence suggests that MDMA-assisted therapy may be of promise for PTSD, and has demonstrated a good safety profile and potential efficacy in alcohol dependence.
This project will evaluate the clinical efficacy and tolerability of MDMA-assisted COPE relative to a placebo-assisted COPE. The investigators hypothesise that MDMA treated patients will be have a reduction in PTSD symptom severity as well as heavy drinking.
The trial will utilise a double blind, randomised, controlled design. A sample of 120 individuals will receive 14 weeks of treatment including 12 COPE sessions and 2 dosing sessions with MDMA (80-160mg) or placebo.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MDMA-assisted prolonged exposure therapy Administration of 80 -160 mg MDMA (80 mg is the minimum dose for the session, the first session has a supplement dose of 40mg offered 60 to 90 minutes following initial 80 mg dose (80-120mg), and the second session has the option of an additional 40mg offered 60 to 90 minutes following initial 80 - 160mg dose). Each session will last approximately 6 to 7 hours. These three 'dosing' sessions will be interspersed between 14 weeks prolonged exposure therapy sessions (COPE). In total there are 12 sessions of COPE therapy across the 14 weeks. |
Behavioral: Prolonged exposure therapy
COPE represents an integration of existing evidence-based manualised CBT interventions for PTSD and substance dependence (see manual DOI: 10.1093/med:psych/9780199334513.001.0001). COPE used in the current study will represent an integration of existing evidence-based manualized CBT interventions for PTSD and substance dependence. COPE only begins when the participant in a safe environment and no longer in contact with the traumatic event/exposure.
COPE employs imaginal and in vivo exposures to treat PTSD and consists of 12 individual 90-minute sessions (ie, 19.5 hours) delivered by a clinical psychologist.
Other Names:
Drug: MDMA
Administration of 80 to 160 mg MDMA across two 'dosing' sessions. Supplemental doses (additional 40mg during first session, additional 40- 80mg during second session) will be dependent on clinician and patient consensus during preparatory period of 'dosing session'. These supplemental amounts will be dispensed 60 to 90 minutes after initial 80 mg dose.
Other Names:
|
| Placebo Comparator: Placebo with prolonged exposure therapy Administration of an inactive placebo during 'dosing' sessions. Each session will last approximately 6 to 7 hours. These three 'dosing' sessions will be interspersed between 14 weeks prolonged exposure therapy sessions (COPE). In total there are 12 sessions of COPE therapy across the 14 weeks |
Behavioral: Prolonged exposure therapy
COPE represents an integration of existing evidence-based manualised CBT interventions for PTSD and substance dependence (see manual DOI: 10.1093/med:psych/9780199334513.001.0001). COPE used in the current study will represent an integration of existing evidence-based manualized CBT interventions for PTSD and substance dependence. COPE only begins when the participant in a safe environment and no longer in contact with the traumatic event/exposure.
COPE employs imaginal and in vivo exposures to treat PTSD and consists of 12 individual 90-minute sessions (ie, 19.5 hours) delivered by a clinical psychologist.
Other Names:
Drug: Placebo
Administration of inactive placebo during two 'dosing' sessions.
|
Outcome Measures
Primary Outcome Measures
- Change in clinician-rated PTSD severity via CAPS-5 from baseline to follow-up appointments [52 weeks]
CAPS-5 is a 30-item questionnaire that corresponds to the DSM-5 criteria for PTSD. Higher scores indicate more PTSD symptoms, and this score is used to diagnose presence of PTSD
- Changes in DSM-5 PTSD symptomology [52 weeks]
As measured by the PCL-5. This self-report questionnaire lists 20-items that assess DSM-5 PTSD criteria. A higher score indicates greater severity
Secondary Outcome Measures
- Number of Heavy Drinking Days per week (HDDs) (>5 standard drinks/day for men; >4 for women) [52 weeks]
This will be measured by the Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
- Absence of any HDD [52 weeks]
Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
Other Outcome Measures
- Mean alcohol consumption per drinking day [52 weeks]
Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
- Change in dependence Severity [52 weeks]
Measured by the Alcohol Dependence Scale. The minimum score is 0 and the maximum score is 47. A higher score indicates more severe dependence.
- Changes in Anxiety [52 weeks]
Measured by cumulative scores on the DASS-21 Anxiety Scale. This scale has a minimum score of 0 and maximum score of 21. A higher score indicates more anxiety.
- Changes in Depression [52 weeks]
Measured by cumulative scores on the DASS-21 Depression Scale. This scale has a minimum score of 0 and maximum score of 21. A higher score indicates greater depression.
- Changes in Stress [52 weeks]
Measured by cumulative scores on the DASS-21 Stress Scale. This scale has a minimum score of 0 and maximum score of 21. A higher score indicates more stress.
- Sleep Disturbances [52 weeks]
As measured by the ISI (Insomnia Severity Index). This Index has a minimum score of 0 and a maximum score of 28. The higher the score indicates more severe insomnia.
- Drinking Dairy [14 weeks]
Daily texts will be sent out to participants querying the amount of alcohol they have consumed. Participant responses to this will be recorded. This will be managed through SEMA software.
- Mood states [14 weeks]
Daily texts will be sent out to participants querying their moods. This will be in line with the POMS instrument (Profile of Mood States).
- Mood following dosing session [11 weeks]
The week following each dosing session will involve calls with participants to complete POMS (profile of mood states)
- Changes in Suicidal Ideation [52 weeks]
Changes in suicidal ideation & behaviours across the treatment period. This will be measured on the C-SRSS (Columbia Suicide Severity Rating Scale). At baseline this will be measured by the baseline version. At each visit following this, this will be recorded on the since last visit version. Higher scores indicate more severe suicidality.
- Changes in Quality of Life [14 weeks]
To assess whether treatment can change quality of life as measured by the short form Health Survey (SF-36). This survey has 36 items that measure 8 domains of health, including: physical functioning, physical role limitations, bodily pain, general health perceptions, energy/vitality, social functioning, emotional role limitations and mental health. The scores are transformed to range from 0 (worst possible health) to 100 (best possible health).
- Changes in Quality of Life [14 weeks]
As measured by the EQ-5D-5L. This instrument measures 5 different domains of life including: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain is assessed by one question. This instrument has a minimum score of 0 (worst possible health) and a maximum score of 1 (best possible health).
- Changes PTSD cognitions [52 weeks]
As measured by the PTCI. This is a 33 question inventory measures negative cognitions about the self & world, as well as self-blame. Higher scores indicate more negative cognitions.
- Changes in use of Health Services [14 weeks]
As measured by the Brief Health Services Use Questionnaire. This questionnaire assesses Health Service Use across the last 3 months. It is a qualitative questionnaire.
- Therapeutic Alliance between therapist [14 weeks]
As measured by the Helping Alliance Questionnaire (HAQ-II). This instrument will be completed by the patient (patient version) and the clinician (clinician version). This outlines how a person may feel or behave in relation to their therapist. Higher scores indicates a better therapeutic alliance.
- COPE Session Rating Scale [14 weeks]
As measured by the session rating scale (SRS). Following each COPE session, both the therapist and participant will complete a brief post-session rating. This scale measures; relationship, goals & topics, approach or method and overall psychotherapy session. Higher scores on each of these indicate a more positive experience.
- Treatment Satisfaction [14 weeks]
As measured by the YES (your experience of service). This instrument is designed to gather information from consumers about their experiences of care.
- Treatment Satisfaction [14 weeks]
As measured by the CSQ-8 (client satisfaction questionnaire). This instrument measures clients satisfaction with treatment. Total scores range from 8 to 32, with the higher number indicating greater satisfaction.
- Measurement of Distress [10 weeks]
As measured by the SUDS (subjective units of distress scale). This instrument will be administered hourly within the dosing sessions. It aims to measure the intensity of the participants feelings and negative internal experiences (like anger, agitation & stress). Higher score indicates a worse outcome.
- Measurement of Drug Effect [10 weeks]
As measured by the DEQ (drug effect questionnaire). This instrument will be administered hourly within the dosing sessions. The questionnaire utilizes a visual analogue scale (VAS) and asks how the participant is feeling right now. This includes questions about drug effect, whether the participant feels high, aversion to any of the drug effects, liking of drug effects & whether the participant wants more. A higher score indicates greater drug effect.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Both AUD and current PTSD according to the DSM-5 criteria, for 6 months or longer with at least moderate severity, according to clinician judgement and CAPS-5
-
Aged ≥18 years old
-
Adequate cognition and English language skills to give valid consent and complete research interviews assessments
-
Willing to give written informed consent
-
Received prior treatment for PTSD or AUD (not including study interventions)
-
Stable housing
-
Able to identify a significant other (such as a family/friend/partner) who could accompany them from clinic/provide transport and/or be contacted by the study team if required
Exclusion Criteria:
-
History of or currently meeting DSM-5 criteria for: current or lifetime psychotic or bipolar disorders or major depression with psychotic features, current eating disorder (assessed via Structured Clinical Interview for DSM-5 - Research Version [SCID-5-RV]). The investigators will screen for personality disorders but suitability will then be confirmed by clinical interview given the prevalence of high scores in this comorbid population
-
Pregnant or lactating (contraception must be used and a sensitive pregnancy test will be performed at baseline and prior to dosing)
-
Concurrent use of psychotropic medication (antidepressants and alcohol pharmacotherapy use considered if assessed by physician and titrated down with 5 half-lives + 1 week washout)
-
Use of, and unable or unwilling to cease, any medications likely to interact with MDMA in the opinion of the physicians and investigators during the trial (low dose opiates are permitted for pain management but not the night before or after MDMA sessions)
-
Substance use disorder other than tobacco (including benzodiazepines, cannabis)
-
Abnormal clinical findings including a history of cardiac disease and dysrhythmia, hypertension and abnormal electrocardiograms including QT prolongation, stroke, liver disease, a history of epilepsy, hyponatraemia, or malignant hyperthermia (controlled hypertension and diabetes type II may be permitted)
-
Suicide risk according to clinician judgement and responses to Columbia Suicide Severity Rating Scale (C-SSRS) and SCID-5-RV. Details surrounding any previous attempts >6 months ago will be gathered whereby attempts related to their trauma/PTSD and/or associated with the use of psychostimulants will contribute to risk assessment and guide trial safety measures if enrolled
-
Clinically unstable systemic medical (e.g., cancer) or psychiatric disorder or condition that might require hospitalisation that precludes trial participation
-
Regular use of ecstasy (e.g. at least twice in last 6 months, or >8 times within the last 2 years, or >5 times within the last 5 years)
-
Enrolled in any other interventional clinical trials or product in the previous two months or over the duration of the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Drug Health Services, Royal Prince Alfred Hospital | Sydney | New South Wales | Australia | 2050 |
| 2 | Turning Point | Richmond | Victoria | Australia | 3121 |
Sponsors and Collaborators
- University of Sydney
- Monash University
- Sydney Local Health District
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- X22-0121