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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-506052-24 | EudraCT Number | ||
| U1111-1293-2654 | Other Identifier | WHO UTN |
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| Name | Class |
|---|---|
| University of Exeter | OTHER |
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The goal of this clinical trial is to investigate the effects of ketamine, in combination with standard inpatient addiction therapy, for adults with depression and alcohol use disorder. After screening and enrollment, participants will undergo baseline assessments of depression, measures of alcohol use and craving, as well as neurocognitive function. Participants will then be randomized to either ketamine (intervention) or midazolam (control). All participants will be admitted for standard inpatient addiction therapy while receiving ketamine or midazolam. Measures on safety, depression and alcohol use disorder will be repeatedly assessed during and after treatment. Final follow-up assessment is scheduled 6 months after baseline assessment.
Depression and alcohol use disorder (AUD) often coexist and can create significant challenges for individuals seeking effective treatment. Traditional treatment approaches have shown limited success in addressing both conditions simultaneously. Ketamine has shown to have promising rapid antidepressant effects and a possible role in the treatment of substance use disorders. By targeting both depression and AUD simultaneously, ketamine has the potential to offer dual benefits, improving depressive symptoms while addressing alcohol cravings or consumption. Furthermore, rapid relief from depressive symptoms may enhance motivation for recovery, reduce the risk of relapse, and improve overall treatment engagement and outcomes. Although ketamine is generally considered safe when administered under medical supervision, the safety profile in individuals with comorbid depression and AUD needs further investigation. The overall objective of this study is to examine the safety and efficacy of ketamine on adults with depression and AUD that are admitted for standard inpatient addiction therapy.
The study will only include adults with at least moderate depression and alcohol use disorder as their primary substance use disorder that are admitted for inpatient addiction therapy. Participants that are unable to give informed consent or have contraindication(s) for ketamine will be excluded.
After screening and enrollment, participants will undergo baseline assessments with measures on depression (using Montgomery-Åsberg Depression Rating Scale (MADRS) and Beck Depression Inventory-II (BDI-II)), alcohol use (using Timeline Follow-Back method (TLFB)), alcohol craving (using Short version of Alcohol Craving Questionnaire (ACQ-Short) and Penn Alcohol Craving Scale (PACS)) and neurocognitive function (using Cambridge Neuropsychological Test Automated Battery (CANTAB)). Participants will then be randomized to intervention group or control group. The intervention group will receive ketamine as four single doses, given biweekly for two weeks. The control group will receive midazolam as active placebo. Participants will undergo several follow-up assessments after treatment (1-2 day(s), 1 week, 2 weeks and 4 weeks after treatment). Final follow-up assessment will be 6 months after baseline.
By using open questions and specific instruments for assessing adverse effects associated with ketamine (using modified version of Ketamine Side Effect Tool (mKSET)), the trial will assess the frequency, severity and duration of any adverse events and severe adverse events. All adverse events will be evaluated with regards to its causal relationship to ketamine. In addition, physician-assessed and patient-assessed tolerability will be registered. Changes in neurocognitive function from baseline will be assessed after treatment.
Changes in depression will be measured several times using rater-blinded MADRS-assessment and self-report instrument (BDI-II). Measures of alcohol use (TLFB), alcohol craving (ACQ-short and PACS), relapse risk and time until relapse will used as measures on alcohol use disorder following treatment. Several exploratory objectives will be examined, including changes in alcohol dependence severity (using Severity of Alcohol Dependence Questionnaire (SADQ)), changes in quality of life (using World Health Organizations brief quality of life questionnaire (WHOQOL-BREF)), changes in self-reported treatment effectiveness (using Treatment Effectiveness Assessment (TEA)) and changes in anxiety (using Generalized Anxiety Disorder scale (GAD-7)). Finally, data on the subjective experience of the treatment (using Ego Dissolution Inventory (EDI), Emotional Breakthrough Inventory (EBI) and Mystical Experience Questionnaire (MEQ30)) will be collected and used in a regression model with baseline measures to assess predictors of treatment response on measures of depression and AUD .
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention group | Experimental | Ketamine, 0,8 mg/kg body weight, given as four single doses (biweekly for two weeks) |
|
| Control group | Active Comparator | Midazolam, 0,8 mg/kg body weight, given as four single doses (biweekly for two weeks) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine Hydrochloride | Drug | Four single-doses, given two times per week for two weeks Dose: 0,8 mg/kg body weight Route of administration: intravenous infusions over 40 minutes |
|
| Measure | Description | Time Frame |
|---|---|---|
| Depression | Change from baseline using rater-blinded Montgomery-Åsberg Depression Rating Scale (MADRS) (range 0-60; higher score indicate worse outcome) | Within 3 days after final treatment session |
| Measure | Description | Time Frame |
|---|---|---|
| Alcohol craving tonic | Penn Alcohol Craving Scale (PACS) (range 0-30; higher score indicate worse outcome) | Repeated measurements from baseline and 1 day, 1 week, 2 weeks and 4 weeks after final treatment session |
| Alcohol craving phasic |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of antidepressant effect (blinded-rater assessed) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) (range 0-60; higher score indicate worse outcome) | From baseline until 6 months after baseline |
| Duration of antidepressant effect (self-report) |
Please contact the project team for a full and detailed list of inclusion/exclusion criteria
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Andreas W Blomkvist, M.D. | Contact | 41694637 | +47 | andreas.wahl.blomkvist@unn.no |
| Ole K Grønli, Assoc Prof | Contact | 91713535 | +47 | ole.k.gronli@unn.no |
| Name | Affiliation | Role |
|---|---|---|
| Ole K Grønli, Assoc Prof | University Hospital of North Norway | Study Director |
| Andreas W Blomkvist, M.D. | University Hospital of North Norway | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Addiction, University Hospital of North Norway | Recruiting | Tromsø | Norway |
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| ID | Term |
|---|---|
| D003863 | Depression |
| D000437 | Alcoholism |
| D016739 | Behavior, Addictive |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
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| ID | Term |
|---|---|
| D007649 | Ketamine |
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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| Midazolam Hydrochloride | Drug | Four single-doses, given two times per week for two weeks Dose: 0,02 mg/kg body weight Route of administration: intravenous infusions over 40 minutes |
|
Alcohol Craving Questionnaire - Short version (ACQ-short) (range 12-84; higher score indicate worse outcome)
| Repeated measurements from baseline and 1 day, 1 week, 2 weeks and 4 weeks after final treatment session |
| Depression response/remission | Rates of response (50% or more reduction in MADRS from baseline) and remission (9 points or less in MADRS) | Repeated measurements from baseline and 1 day, 1 week, 2 weeks and 4 weeks after final treatment session |
| Relapse risk | Incidence of relapse in each group (defined as two or more consecutive heavy drinking days) | From baseline until 6 months after baseline |
| Time until relapse | Average time from final treatment session until relapse | From baseline until 3 and 6 months after baseline |
Change in the Beck Depression Inventory-II (BDI-II) (Range 0-63; higher score indicate worse outcome) |
| From baseline until 6 months after baseline |
| Tolerability using the ketamine side effect tool (KSET) | Physician-reported tolerability of each treatment session (good, moderate and poor) | Up to 1 month |
| Tolerability using the ketamine side effect tool (KSET) | Patient-reported tolerability of each treatment session (good, moderate and poor) | Up to 1 month |
| Cambridge Neuropsychological Test Automated Battery (CANTAB): Stop Signal Task (SST); Spatial Working Memory (SWM) task; Intra-Extra Dimensional Shift (IED) task; Paired Associates Learning (PAL) task; Emotional Bias Task (EBT) | Assess within- and between-group changes in neurocognitive function from baseline to within three days from the final treatment session: SST (Range 0-1000; Lower score indicate better outcome); SWM (Range: 2-14; Lower score indicates better outcome); IED (Range: 0-402; Lower score indicates better outcome); PAL (Range: 0-70; Lower score indicates better outcome); EBT (Range: 0-15; Higher score indicates better outcome (more happy)) | Within 3 days after final treatment session |
| Adverse reaction frequency | Frequency of adverse reactions | Up to 6 months |
| Adverse reaction severity | Number of mild, moderate and severe adverse reactions | Up to 6 months |
| D064419 |
| Chemically-Induced Disorders |
| D001523 | Mental Disorders |
| D003192 | Compulsive Behavior |
| D007175 | Impulsive Behavior |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |