Ketamine for the Treatment for Alcohol Use Disorder in the Emergency Department: A Pilot Double-blind, Placebo-controlled Randomized Clinical Trial
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Sponsor
- Brigham and Women's Hospital
- Locations
- 1
- Primary Endpoint
- Safety of administering ketamine in the emergency department (ED) for alcohol use disorder (AUD) patients seeking detoxification
Study Overview
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.
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
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •English speaking adults aged 18 and above
- •Diagnosed with DSM5 alcohol use disorder, severe
- •Admitted to BWF inpatient withdrawal management unit (Addiction Recovery Program)
Exclusion Criteria
- •Any psychotic disorder, bipolar disorder, active suicidality or homicidality
- •Inability to perform consent due to impaired mental status
- •Clinical Institute Withdrawal Assessment (CIWA) score > 20 at any point in the ED
- •Alcohol withdrawal seizure prior to or during the ED visit
- •Systolic blood pressure persistently elevated above 180mmHg, or heart rate >130bmp, in the ED
- •History of hypersensitivity to ketamine, or experience of emergence reaction
- •History of any illicit or recreational use of ketamine
- •Receipt of ketamine treatment for depression in the past 3 months
- •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
- •History within 6 months of head trauma, stroke, or myocardial infarction
- •Liver dysfunction with LFTs >3x upper normal limit
- •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)
Arms & Interventions
Ketamine
This arm will receive ketamine (n=25)
Intervention: Ketamine (Drug)
Placebo
This arm will receive the saline placebo (n=25)
Intervention: Saline (Drug)
Outcomes
Primary Outcomes
Safety of administering ketamine in the emergency department (ED) for alcohol use disorder (AUD) patients seeking detoxification
Time Frame: Outcomes will be assessed throughout the inpatient admission, on average 3-5 days and throughout duration of study.
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 Outcomes
- Craving for ketamine(Assessed during the inpatient admission, on average 3-5 days; 7, 14, 28 days and 3, 6, and 12 months after treatment)
- Craving for alcohol(Assessed during the inpatient admission, on average 3-5 days; 7, 14, 28 days and 3, 6, and 12 months after treatment)
- Ketamine in Urine(At baseline and 28 days after treatment)
- Urine ethylglucuronide(At baseline and at 28 days after treatment)
- Phosphatidylethanol (PEth)(At baseline and at 28 days after treatment)
- Behavior Change Mechanisms(Once during inpatient treatment and at 28 days after treatment)
- Depression(At baseline, each day during treatment (3-5 Days on average), 7, 14, 28 days and 3, 6, and 12 months after treatment)
- Alcohol withdrawal(Assessed during the inpatient admission, on average 3-5 days.)
- Preliminary efficacy of ketamine on engagement with addiction treatment(Measured at baseline, 28 days, and 3, 6, and 12 months post treatment.)
- Dissociative effects(Baseline, daily during inpatient (average 3-5 days), 28 days, and 3, 6, and 12 months after inpatient treatment.)
- Cue-induced craving(Assessed during the inpatient admission, on average 3-5 days; 28 days after treatment)
- Preliminary efficacy of ketamine on days to alcohol relapse(7, 14, 28 days and 3, 6, and 12 months after treatment)
- Preliminary efficacy of ketamine on proportion heavy drinking days(7, 14, 28 days and 3, 6, and 12 months after treatment)
- Anxiety(At baseline, each day during treatment (3-5 Days on average), 7, 14, 28 days and 3, 6, and 12 months after treatment)
- Spirituality(Baseline, once during treatment, and at 28 days post treatment.)
- Suicidal Ideation(At baseline, each day during treatment (3-5 Days on average), 7, 14, 28 days and 3, 6, and 12 months after treatment)
- Post Traumatic Stress(Once during treatment)
- Study Drug Side Effects(At baseline, each day during treatment (3-5 Days on average), 7, 14, 28 days and 3, 6, and 12 months after treatment)
Investigators
Joji Suzuki, MD
Director, Division of Addiction Psychiatry
Brigham and Women's Hospital