An Open-label Pilot Evaluation of Ketamine-Enhanced Psychotherapy in Individuals With Alcohol Use Disorder (AUD) and Co-morbid Major Depressive Disorder (MDD)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Feasibility will be assessed through recruitment rates, retention to follow-up, session attendance, and treatment adherence.
研究概览
简要总结
To assess the safety, feasibility and preliminary efficacy of ketamine-enhanced therapy (KET) for alcohol use disorder (AUD) and comorbid major depressive disorder (MDD) in an open-label, single arm, pilot clinical trial.
详细描述
New strategies for the treatment of alcohol use disorder (AUD) and co-morbid major depressive disorder (MDD) are urgently required. This population represents a high-risk group that has largely been excluded from addiction-focused trials despite its clinical complexity and poor response to standard interventions.
Recent early phase studies have shown that ketamine-enhanced psychotherapy (KET) can reduce alcohol consumption, enhance motivation and alleviate depressive symptoms. Effects have been shown to be particularly pronounced among participants who also received motivational enhancement therapy, suggesting a synergistic effect between ketamine and psychotherapy.
Emerging evidence suggests that KET may be of promise for AUD, and has demonstrated a good safety profile and potential efficacy in alcohol dependence. However, no trials to date have specifically targeted AUD and co-morbid MDD.
This project will assess the clinical safety, feasibility and preliminary efficacy of KET in individuals with AUD and co-morbid MDD. The investigators hypothesise that KET will be safe and feasible to deliver in this population, and expect to observe preliminary improvements in alcohol consumption, depressive symptoms, and treatment engagement. The KET intervention is also anticipated to be well tolerated with high levels of session attendance and acceptable rates of adverse events.
The trial will utilise an open-label, single-arm, pilot clinical trial design. A sample of 20 individuals will receive 6 weeks of treatment including 6 manualized cognitive-behavioural therapy sessions and 3 dosing sessions with Ketamine administered at 2 week intervals (0.7mg/kg initially up).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Moderate to severe AUD according to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V) criteria
- •Presence of current Major Depressive Disorder (MDD), according to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V) criteria
- •Expressed motivation to reduce or cease alcohol consumption.
- •Consumed at least 21 standard drinks per week or 2 HDD per week (≥5 standard drinks/day for men; ≥4 for women) in the month prior to screening
- •Adequate cognition and English language skills to give valid consent and complete research interviews
- •Stable housing
- •Willingness to give written informed consent.
- •Willingness to comply with study procedures and attend scheduled visits.
排除标准
- •DSM-5 diagnosis of current or past psychotic disorder, bipolar I disorder, or substance-induced psychosis.
- •Current acute suicidality, defined as high risk by the Columbia Suicide Severity Rating Scale (C-SSRS) or clinical judgment or attempts in the past 6 months.
- •DSM-5 diagnosis of current or past moderate-to-severe ketamine or other dissociative drug use disorder.
- •Use of ketamine (prescribed or non-prescribed) in the previous 4 weeks.
- •Enrolment in another interventional clinical trial that may interfere with safety, data quality, or trial participation.
- •Pregnant or breastfeeding, or planning to become pregnant during the course of the study.
- •Significant uncontrolled medical conditions, including but not limited to:
- •Severe or poorly controlled hypertension (>160/100 mmHg)
- •Severe cardiovascular disease (e.g., heart failure, recent myocardial infarction, dysrhythmia)
- •History of stroke, cerebral trauma, or intracranial mass/haemorrhage
- •Severe hepatic impairment (e.g., MELD ≥10) or end-stage liver disease, bladder or kidney disease
- •Clinically significant alcohol withdrawal at screening (e.g., CIWA-Ar ≥10, history of delirium tremens).
- •History of heightened intracranial pressure, seizures, or diagnosed seizure disorder (except childhood febrile seizures).
- •Known hypersensitivity to ketamine or any excipients.
- •Concurrent use of psychotropic medications (other than stable-dose antidepressants ≥4 weeks).
- •Active substance use disorder (moderate or severe) other than nicotine or caffeine; stable opioid use disorder permitted if on maintenance therapy (with strict stability criteria).
- •Inability or unwillingness to comply with study procedures, judged by the principal investigator.
- •Any clinically significant medical or psychiatric condition that, in the judgment of the Principal Investigator, poses a safety risk or could confound study results or hinder protocol adherence.
研究组 & 干预措施
Ketamine-enhanced therapy (KET): sub-anesthetic ketamine plus structured psychotherapy
- x CBT session (Week 1)
Dose 1: 1x Sub-anaesthetic subcutaneous dose of racemic ketamine (initially 0.7mg/kg, up to a potential maximum of 1.2mg/kg, at the discretion of the principal investigator and permitted based on tolerability) (Week 2) 2. x CBT sessions (Week 2 - 3)
Dose 2: 1x Sub-anaesthetic subcutaneous dose of racemic ketamine (initially 0.7mg/kg, up to a potential maximum of 1.2mg/kg, at the discretion of the principal investigator and permitted based on tolerability (Week 4)
2 x CBT sessions (Week 4 - 5)
Dose 3: 1x Sub-anaesthetic subcutaneous dose of racemic ketamine (initially 0.7mg/kg, up to a potential maximum of 1.2mg/kg, at the discretion of the principal investigator and permitted based on tolerability (Week 6)
1x CBT session (Week 6)
干预措施: Ketamine (Drug)
Ketamine-enhanced therapy (KET): sub-anesthetic ketamine plus structured psychotherapy
- x CBT session (Week 1)
Dose 1: 1x Sub-anaesthetic subcutaneous dose of racemic ketamine (initially 0.7mg/kg, up to a potential maximum of 1.2mg/kg, at the discretion of the principal investigator and permitted based on tolerability) (Week 2) 2. x CBT sessions (Week 2 - 3)
Dose 2: 1x Sub-anaesthetic subcutaneous dose of racemic ketamine (initially 0.7mg/kg, up to a potential maximum of 1.2mg/kg, at the discretion of the principal investigator and permitted based on tolerability (Week 4)
2 x CBT sessions (Week 4 - 5)
Dose 3: 1x Sub-anaesthetic subcutaneous dose of racemic ketamine (initially 0.7mg/kg, up to a potential maximum of 1.2mg/kg, at the discretion of the principal investigator and permitted based on tolerability (Week 6)
1x CBT session (Week 6)
干预措施: Cognitive Behavioural Therapy (Behavioral)
结局指标
主要结局
Feasibility will be assessed through recruitment rates, retention to follow-up, session attendance, and treatment adherence.
时间窗: 22 weeks
Feasibility outcomes will be assessed by the traffic light framework may be applied to guide progression decisions for future trials for each of the following variables: (i) time taken to recruit the sample; (ii) proportion of ineligible participants at (a) pre tele-screening and (b) onsite screening; (iii) number of participants who receive (a) at least two doses of ketamine and (b) at least four CBT sessions; (iv) retention rate over the trial. As this is the first study of its kind in this population and pilot studies are not generalisable to other contexts, these will be assessed and reported descriptively. Results will be synthesised in consideration of the feasibility to progress to larger studies, taking into account the measures described above. Specifically, based on our prior trials of CBT, pharmaco-assisted therapy and complex S9 trials, the following would be an estimation of failure to progress to full trial for each variable and when taken together: (i) \> 24 months; (ii)
Safety will be assessed through the frequency, severity, and relatedness of adverse events (AEs), including dissociation, affective destabilisation, and vital sign abnormalities.
时间窗: 22 weeks
Safety outcomes including adverse events (AEs), serious adverse events (SAEs), and vital sign abnormalities, will be summarised descriptively across the study period. Feasibility outcomes (e.g., recruitment and retention rates, session attendance) will be analysed using proportions with corresponding 95% confidence intervals.
次要结局
- Number of Heavy Drinking Days per week (HDDs) (>5 standard drinks/day for men; >4 for women) and total alcohol consumption.(22 weeks)
- Change in depressive symptoms measured by MADRS and DASS-21.(22 weeks)
- Changes in suicidal ideation (weekly monitoring) using the Columbia Suicide Severity Rating Scale (C-SSRS).(22 weeks)
- Changes in Positive and Negative Mood States(Week 2 (integration session 1), Week 4 (integration session 2), Week 6 (optional - at ketamine dose 3), Week 6 (integration session 3 and end of treatment))
研究者
Kirsten Morley BPsych MPH PhD
Professor
South West Sydney Local Health District