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

NCT ID: NCT07247370

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-10
• Study Completion Date: 2027-12-10

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.

Detailed Description

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).

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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)

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: 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).

Cognitive Behavioural Therapy

Intervention Type: 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.

Interventions

Ketamine

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).

Intervention Type: DRUG

Cognitive Behavioural Therapy

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.

Intervention Type: BEHAVIORAL

Other Intervention Names

CBT; Psychotherapy

Eligibility Criteria

Inclusion Criteria

1. Moderate to severe AUD according to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V) criteria

2. Presence of current Major Depressive Disorder (MDD), according to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V) criteria

3. Expressed motivation to reduce or cease alcohol consumption.

4. 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

5. Age 18-70

6. Adequate cognition and English language skills to give valid consent and complete research interviews

7. Stable housing

8. Willingness to give written informed consent.

9. Willingness to comply with study procedures and attend scheduled visits.

Exclusion Criteria

1. DSM-5 diagnosis of current or past psychotic disorder, bipolar I disorder, or substance-induced psychosis.

2. 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.

3. DSM-5 diagnosis of current or past moderate-to-severe ketamine or other dissociative drug use disorder.

4. Use of ketamine (prescribed or non-prescribed) in the previous 4 weeks.

5. Enrolment in another interventional clinical trial that may interfere with safety, data quality, or trial participation.

6. Pregnant or breastfeeding, or planning to become pregnant during the course of the study.

7. 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

8. Clinically significant alcohol withdrawal at screening (e.g., CIWA-Ar ≥10, history of delirium tremens).

9. History of heightened intracranial pressure, seizures, or diagnosed seizure disorder (except childhood febrile seizures).

10. Known hypersensitivity to ketamine or any excipients.

11. Concurrent use of psychotropic medications (other than stable-dose antidepressants ≥4 weeks).

12. 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).

13. Inability or unwillingness to comply with study procedures, judged by the principal investigator.

14. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Sydney, Sydney, Australia

UNKNOWN

Sponsor Role: collaborator

South West Sydney Local Health District

OTHER

Sponsor Role: lead

Responsible Party

Kirsten Morley BPsych MPH PhD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Drug Health Services, Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

Countries

Australia

Central Contacts

Kirsten C Morley, PhD

Role: CONTACT

Kirsten.morley@sydney.edu.au

+61295153636

Ellen Towers

Role: CONTACT

ellen.towers@sydney.edu.au

Facility Contacts

Kirsten Morley, PhD

Role: primary

Kirsten.morley@sydney.edu.au

Central Contact Line

Role: backup

0459877108

Other Identifiers

X25-0138

Identifier Type: -

Identifier Source: org_study_id