Ketamine-Enhanced Therapy for Individuals With Alcohol Use Disorder and Depression: A Pilot Study (KET-DUAL)

NCT07247370 | Not Yet Recruiting Phase 1

• 1 other identifier: X25-0138
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alcohol Use Disorder (AUD); Major Depressive Disorder (MDD); Comorbidities and Coexisting Conditions

Keywords

Ketamine-enhanced psychotherapy; Open-label; Single-arm; Ketamine; Concurrent Treatment of AUD and comorbid MDD; Alcohol Use Disorder (AUD); Major Depressive Disorder (MDD)

Outcome Measures

Primary Outcomes (2)

• Feasibility will be assessed through recruitment rates, retention to follow-up, session attendance, and treatment adherence.

  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)

  22 weeks

• Safety will be assessed through the frequency, severity, and relatedness of adverse events (AEs), including dissociation, affective destabilisation, and vital sign abnormalities.

  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.

  22 weeks

Secondary Outcomes (4)

• 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)

Other Outcomes (21)

• Changes in Depression

  22 weeks

• Changes in Anxiety

  22 weeks

• Changes in Stress

  22 weeks

Study Arms (1)

Ketamine-enhanced therapy (KET): sub-anesthetic ketamine plus structured psychotherapy

EXPERIMENTAL

1. 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)

Drug: Ketamine; Behavioral: Cognitive Behavioural Therapy

Interventions

Ketamine DRUG

Subcutaneous administration of of Ketamine across 3 dosing sessions (at week 2, 4 and 6). Dosing adjustments are permitted based on tolerability, with a minimum dose of 0.7mg/kg and a potential maximum of 1.2 mg/kg, at the discretion of the principal investigator (previous studies have found efficacy at 0.8mg/kg for AUD).

Ketamine-enhanced therapy (KET): sub-anesthetic ketamine plus structured psychotherapy

Cognitive Behavioural Therapy BEHAVIORAL

This study uses a manualized CBT program adapted for ketamine-assisted context. It integrates evidence-based CBT for substance use and depression with principles of psychedelic-assisted therapy, including "set and setting." considerations central to psychedelic-assisted therapy. The therapist manual includes guidance on psychological preparation, intention-setting, integration, and therapeutic framing of ketamine experiences. Participants receive six 90-minute sessions over six weeks, delivered by trained health professionals (e.g., psychologists, mental health nurses, social workers) with specific training in the adapted CBT protocol and psychedelic-assisted therapy. Sessions include: Preparation (Week 1): Review of alcohol use, treatment goals, and ketamine orientation. Integration (Weeks 2, 4, 6): Post-dose processing and linking experience to recovery goals occurring 24-48 hours post dose. Continued CBT (Weeks 3, 5): Coping strategies, goal setting, and relapse prevention.

Also known as: CBT, Psychotherapy

Ketamine-enhanced therapy (KET): sub-anesthetic ketamine plus structured psychotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Age 18-70
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• South West Sydney Local Health District: lead
• The University of Sydney, Sydney, Australia: collaborator

Study Sites (1)

Drug Health Services, Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

MeSH Terms

Conditions

Alcoholism; Depressive Disorder, Major

Interventions

Ketamine; Cognitive Behavioral Therapy; Psychotherapy

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Depressive Disorder; Mood Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Behavior Therapy; Behavioral Disciplines and Activities

Central Study Contacts

Kirsten C Morley, PhD

CONTACT

+61295153636; Kirsten.morley@sydney.edu.au

Ellen Towers

CONTACT

ellen.towers@sydney.edu.au

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Open-label, single-arm, pilot study assessing the safety, feasibility, and preliminary efficacy of ketamine-enhanced therapy (KET) for individuals with alcohol use disorder (AUD) and co-morbid major depressive disorder (MDD) Participants will receive 3 doses of sub-anaesthetic ketamine combined with structured psychotherapy over six weeks, followed by follow-up assessments.

Study Record Dates

• First Submitted: November 16, 2025
• First Posted: November 25, 2025
• Study Start: December 10, 2025
• Primary Completion (Estimated): April 10, 2027
• Study Completion (Estimated): December 10, 2027
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)