CAPS-5 is a structured diagnostic interview with excellent psychometric properties and diagnostic efficiency and used widely in MDMA-assisted PTSD studies. The CAPS-5 will be administered by independent evaluators blind to treatment condition.
MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder
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.
Intervention / Treatment
Randomised, double-blind between group comparison of change in PTSD symptoms and alcohol consumption
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Prolonged exposure therapy (BEHAVIORAL)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 manualised 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 (i.e. 19.5 hours) delivered by a clinical psychologist.
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MDMA (DRUG)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 participant consensus during preparatory period of 'dosing session'. These supplemental amounts will be dispensed 60 to 90 minutes after initial 80 mg dose.
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Control (DRUG)Administration of niacin 250mg or niacin-matched placebo during two 'dosing' sessions.
Condition or Disease
- PTSD
- Alcohol Use Disorder
- Alcohol Dependence
- Post-Traumatic Stress Disorder
- Comorbidities and Coexisting Conditions
Phase
Study Design
| Study type: | INTERVENTIONAL |
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| Status: | Not yet recruiting |
| Study results: | No Results Available |
| Enrollment: | 120 (ESTIMATED) |
| Allocation: | Randomized |
| Primary Purpose: | Treatment |
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Clinical Trial Dates
| Start date: | Sep 25, 2023 | ESTIMATED |
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| Primary Completion: | May 01, 2026 | ESTIMATED |
| Completion Date: | May 01, 2026 | ESTIMATED |
| Study First Posted: | Feb 02, 2023 | ACTUAL |
| Last Updated: | Sep 12, 2023 |
Sponsors / Collaborators
Lead Sponsor:
University of Sydney
Responsible Party:
Kirsten Morley
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 control-assisted COPE. Active control used in this study is niacin. The investigators hypothesise that MDMA treated participants 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 control (niacin 250mg).
This project will evaluate the clinical efficacy and tolerability of MDMA-assisted COPE relative to a control-assisted COPE. Active control used in this study is niacin. The investigators hypothesise that MDMA treated participants 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 control (niacin 250mg).
Participant Groups
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4x COPE sessions Dose 1: 2x MDMA capsules (80mg) + 1x niacin-matched placebo capsule Optional supplementary dispense: 1x MDMA capsule (40mg) 4x COPE sessions Dose 2: 2x MDMA capsules (80mg) + 1x niacin-matched placebo capsule Optional supplementary dispense: 1x OR 2x white MDMA capsule (40 or 80mg) 4x COPE sessions
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4x COPE sessions Dose 1: 2x MDMA-matched placebo capsules + 1x niacin capsule (250mg) Optional supplementary dispense: 1x MDMA-matched placebo capsule 4x COPE sessions Dose 2: 2x MDMA-matched placebo capsules + 1x niacin capsule (250mg) Optional supplementary dispense: 1x OR 2x MDMA-matched placebo capsule 4x COPE sessions
Eligibility Criteria
| Sex: | All |
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| Minimum Age: | 18 |
| Age Groups: | Adult / Older Adult |
| Healthy Volunteers: | Yes |
Inclusion Criteria:
1. Both AUD and current PTSD according to the DSM-5 criteria, for 6 months or longer with at least moderate severity, according to investigator judgement and CAPS-5
2. Aged ≥18 years old
3. Adequate cognition and English language skills to give valid consent and complete research interviews assessments
4. Willing to give written informed consent
5. Received prior treatment for PTSD or AUD (not including study interventions)
6. Stable housing
7. 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:
1. History of, or currently meeting, DSM-5 criteria for:
* current or lifetime psychotic or bipolar disorders, or
* major depression with psychotic features Assessed via Structured Clinical Interview for DSM-5 - Research Version (SCID-5-RV). Potential participants will be screened for personality disorders but suitability will then be confirmed by clinical interview given the prevalence of high scores in this comorbid population
2. Pregnant or lactating (contraception must be used and a sensitive pregnancy test will be performed at baseline and prior to dosing)
3. Significant alcohol withdrawal (current Clinical Institute Withdrawal Assessment for Alcohol \[CIWA-Ar\] score ≥10, including history of delirium tremens or alcohol withdrawal seizures).
4. 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)
5. 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)
6. Substance use disorder other than tobacco (e.g. benzodiazepines, cannabis)
7. Abnormal clinical findings including a history of, or current: cardiac disease and/or dysrhythmia, uncontrolled hypertension or severe hypotension, abnormal electrocardiogram findings, stroke, liver disease, a history of epilepsy, hyponatraemia, or malignant hyperthermia (controlled hypertension and diabetes type II may be permitted)
8. Suicide risk according to clinician judgement and responses to Columbia Suicide Severity Rating Scale-Lifetime (C-SSRS-L) 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
9. Clinically unstable systemic medical (e.g., cancer) or psychiatric disorder or condition that might require hospitalisation that precludes trial participation
10. Regular use of ecstasy (e.g. at least twice in last 6 months, or \>10 times within the last 5 years)
11. Enrolled in any other interventional clinical trials in the previous two months or over the duration of the study
1. Both AUD and current PTSD according to the DSM-5 criteria, for 6 months or longer with at least moderate severity, according to investigator judgement and CAPS-5
2. Aged ≥18 years old
3. Adequate cognition and English language skills to give valid consent and complete research interviews assessments
4. Willing to give written informed consent
5. Received prior treatment for PTSD or AUD (not including study interventions)
6. Stable housing
7. 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:
1. History of, or currently meeting, DSM-5 criteria for:
* current or lifetime psychotic or bipolar disorders, or
* major depression with psychotic features Assessed via Structured Clinical Interview for DSM-5 - Research Version (SCID-5-RV). Potential participants will be screened for personality disorders but suitability will then be confirmed by clinical interview given the prevalence of high scores in this comorbid population
2. Pregnant or lactating (contraception must be used and a sensitive pregnancy test will be performed at baseline and prior to dosing)
3. Significant alcohol withdrawal (current Clinical Institute Withdrawal Assessment for Alcohol \[CIWA-Ar\] score ≥10, including history of delirium tremens or alcohol withdrawal seizures).
4. 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)
5. 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)
6. Substance use disorder other than tobacco (e.g. benzodiazepines, cannabis)
7. Abnormal clinical findings including a history of, or current: cardiac disease and/or dysrhythmia, uncontrolled hypertension or severe hypotension, abnormal electrocardiogram findings, stroke, liver disease, a history of epilepsy, hyponatraemia, or malignant hyperthermia (controlled hypertension and diabetes type II may be permitted)
8. Suicide risk according to clinician judgement and responses to Columbia Suicide Severity Rating Scale-Lifetime (C-SSRS-L) 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
9. Clinically unstable systemic medical (e.g., cancer) or psychiatric disorder or condition that might require hospitalisation that precludes trial participation
10. Regular use of ecstasy (e.g. at least twice in last 6 months, or \>10 times within the last 5 years)
11. Enrolled in any other interventional clinical trials in the previous two months or over the duration of the study
Primary Outcomes
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PCL-5 has excellent psychometric characteristics for a secondary indicator of PTSD symptom severity.
Secondary Outcomes
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This will be measured by the Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
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Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
Other Outcomes
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Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
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Measured by the Alcohol Dependence Scale. The minimum score is 0 and the maximum score is 47. A higher score indicates more severe dependence.
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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.
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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.
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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.
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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.
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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.
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Daily texts will be sent out to participants querying their moods. This will be in line with the POMS instrument (Profile of Mood States).
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The week following each dosing session will involve calls with participants to complete POMS (profile of mood states)
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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.
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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).
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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.
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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.
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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.
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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.
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As measured by the YES (your experience of service). This instrument is designed to gather information from consumers about their experiences of care.
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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.
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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.
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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.
More Details
| NCT Number: | NCT05709353 |
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| Other IDs: | X22-0121 |
| Study URL: | https://clinicaltrials.gov/study/NCT05709353 |
Last updated: Sep 29, 2023