Ketamine for the Treatment for Alcohol Use Disorder in the ED
Study Details
Study Description
Brief Summary
The investigators' approach is to conduct a pilot double-blind, placebo-controlled randomized clinical trial with individuals with alcohol use disorder (AUD) seeking inpatient alcohol detoxification in the emergency department (ED) to receive either intravenous ketamine or saline placebo. The primary aim is to evaluate the intervention's safety. The secondary aim is to evaluate the preliminary efficacy of alcohol-related outcomes.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This is a pilot double-blind, placebo-controlled randomized clinical trial of 50 individuals with alcohol use disorder (AUD) presenting to the emergency department (ED) seeking inpatient detoxification to receive either a single infusion of ketamine 0.8mg/kg (n=25) or saline placebo (n=25). The study will be conducted at Brigham and Women's Faulkner Hospital (BWF), an urban, 171-bed hospital located in Boston, MA, and a major teaching hospital for Harvard Medical School (HMS). Participants will be randomized in a double-blind fashion to receive either ketamine or saline placebo in the ED. All participants will receive the institution's standard treatment, which includes detoxification, intensive psychosocial support, and referral to outpatient treatment. The intervention (ketamine) will consist of a single infusion of ketamine in the ED at a dose of 0.8mg/kg over 40 minutes, and the placebo will be a 0.9% saline solution also administered over 40 minutes. To determine the safety of administering ketamine the investigators will measure the incidence of severe adverse events (AE), defined as either hypertensive urgency (systolic blood pressure>180mmHg or diastolic blood pressure>110mmHg) or tachycardia (heart rate>130bpm). The investigators will also assess side effects, alcohol withdrawal, and craving for alcohol and ketamine. To determine the preliminary efficacy of ketamine on alcohol-related outcomes, the investigators will measure the proportion of abstinent days during the follow-up assessed using Timeline Follow-Back (TLFB). The investigators will also measure days to relapse, the proportion of heavy drinking days, engagement with addiction treatment, urine ketamine, and alcohol biomarkers (urine ethylglucuronide and serum phosphatidylethanol) at 28-days. The investigators hypothesize that results will show adequate safety and that those receiving ketamine, compared to placebo, will not experience more side effects, worse withdrawal, or greater alcohol or ketamine craving. The investigators also hypothesize that those receiving ketamine will report better drinking outcomes compared to placebo.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ketamine This arm will receive ketamine (n=25) |
Drug: Ketamine
The intervention will consist of a single infusion of ketamine in the ED at a dose of 0.8mg/kg over 40 minutes.
|
| Placebo Comparator: Placebo This arm will receive the saline placebo (n=25) |
Drug: Saline
The placebo will be a 0.9% saline solution administered over 40 minutes.
|
Outcome Measures
Primary Outcome Measures
- Safety of administering ketamine in the emergency department (ED) for alcohol use disorder (AUD) patients seeking detoxification [Outcomes will be assessed throughout the inpatient admission, on average 3-5 days.]
The incidence of severe adverse events (AE), defined as either hypertensive urgency (systolic blood pressure>180mmHg or diastolic blood pressure>110mmHg) or tachycardia (heart rate>130bpm). Adequate safety will be defined as <10% of participants experiencing severe AEs.
Secondary Outcome Measures
- Dissociative effects [Assessed during the inpatient admission, on average 3-5 days.]
Clinician-Administered Dissociative States Scale (CADSS)
- Psychotic symptoms [Assessed during the inpatient admission, on average 3-5 days.]
Brief Psychiatric Rating Scale
- Alcohol withdrawal [Assessed during the inpatient admission, on average 3-5 days.]
Clinical Institute Withdrawal Assessment (CIWA)
- Craving for alcohol [Assessed during the inpatient admission, on average 3-5 days; 28 days after treatment]
Alcohol craving questionnaire
- Craving for ketamine [Assessed during the inpatient admission, on average 3-5 days; 28 days after treatment]
Visual analog scale
- Cue-induced craving [Assessed during the inpatient admission, on average 3-5 days; 28 days after treatment]
Visual analog scale will be used to rate the craving following a standardized protocol used to assess cue reactivity. The cue exposure procedure will end with a standardized relaxation exercise.
- Preliminary efficacy of ketamine on days to alcohol relapse [28 days after treatment]
Days to relapse will be measured by using the Timeline Follow-Back (TLFB).
- Preliminary efficacy of ketamine on proportion heavy drinking days [28 days after treatment]
The proportion of heavy drinking days will be measured by using the Timeline Follow-Back (TLFB).
- Preliminary efficacy of ketamine on engagement with addiction treatment [28 days after treatment]
The Alcoholic Anonymous Affiliation Scale (AAAS) will be used to measure engagement with addiction treatment. This is a 9-item scale to measure the degree of involvement with Alcoholics Anonymous.
- Ketamine in Urine [28 days after treatment]
Urine drug screen that includes ketamine will be assessed.
- Urine ethylglucuronide [At baseine and at 28 days after treatment]
Urine ethylglucuronide (EtG) will be obtaeined
- Phosphatidylethanol (PEth) [At baseine and at 28 days after treatment]
Serum phosphatidylethanol (PEth)
- Behavior Change Mechanisms [28 days after treatment]
Mechanisms of behavior change will be measured using tools from the Science of Behavior Change Measures.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
English speaking adults aged 18 and above
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Diagnosed with DSM5 alcohol use disorder, severe
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Admitted to BWF inpatient withdrawal management unit (Addiction Recovery Program)
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Able to identify 2 individuals who can act as points of contact following discharge from the hospital
Exclusion Criteria:
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Any psychotic disorder, bipolar disorder, active suicidality or homicidality
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Inability to perform consent due to impaired mental status
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Clinical Institute Withdrawal Assessment (CIWA) score > 20 at any point in the ED
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Alcohol withdrawal seizure prior to or during the ED visit
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Systolic blood pressure persistently elevated above 180mmHg, or heart rate >130bmp, in the ED
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History of hypersensitivity to ketamine, or experience of emergence reaction
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History of any illicit or recreational use of ketamine
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Receipt of ketamine treatment for depression in the past 3 months
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History of DSM5 hallucinogen use disorder, intracranial mass or bleed, porphyria, thyrotoxicosis, seizure disorder other than from alcohol withdrawal, liver cirrhosis, renal failure, obstructive lung disease, or sleep apnea
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History within 6 months of head trauma, stroke, or myocardial infarction
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Liver dysfunction with LFTs >3x upper normal limit
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Current use of medications with known drug-drug interactions with ketamine (i.e., St. John's Wort, theophylline, opioid analgesics, CNS depressants other than benzodiazepines or phenobarbital)
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Pregnant
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Brigham and Women's Hospital
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2022P002550
- 1R21AA030372-01A1