Clinical trial NCT05661669: Ketamine for the Treatment for Alcohol Use Disorder in the ED
Official title: Ketamine for the Treatment for Alcohol Use Disorder in the Emergency Department: A Pilot Double-blind, Placebo-controlled Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Alcohol Use Disorder
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2022-12-22
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)
* Pregnant

Primary outcomes:
measure: Safety of administering ketamine in the emergency department (ED) for alcohol use disorder (AUD) patients seeking detoxification
timeFrame: Outcomes will be assessed throughout the inpatient admission, on average 3-5 days and throughout duration of study.
Secondary outcomes:
measure: Dissociative effects
timeFrame: Baseline, daily during inpatient (average 3-5 days), 28 days, and 3, 6, and 12 months after inpatient treatment.
measure: Alcohol withdrawal
timeFrame: Assessed during the inpatient admission, on average 3-5 days.
measure: Craving for alcohol
timeFrame: Assessed during the inpatient admission, on average 3-5 days; 7, 14, 28 days and 3, 6, and 12 months after treatment
measure: Craving for ketamine
timeFrame: Assessed during the inpatient admission, on average 3-5 days; 7, 14, 28 days and 3, 6, and 12 months after treatment
measure: Cue-induced craving
timeFrame: Assessed during the inpatient admission, on average 3-5 days; 28 days after treatment
measure: Preliminary efficacy of ketamine on days to alcohol relapse
timeFrame: 7, 14, 28 days and 3, 6, and 12 months after treatment
measure: Preliminary efficacy of ketamine on proportion heavy drinking days
timeFrame: 7, 14, 28 days and 3, 6, and 12 months after treatment
measure: Preliminary efficacy of ketamine on engagement with addiction treatment
timeFrame: Measured at baseline, 28 days, and 3, 6, and 12 months post treatment.
measure: Ketamine in Urine
timeFrame: At baseline and 28 days after treatment
measure: Urine ethylglucuronide
timeFrame: At baseline and at 28 days after treatment
measure: Phosphatidylethanol (PEth)
timeFrame: At baseline and at 28 days after treatment
measure: Behavior Change Mechanisms
timeFrame: Once during inpatient treatment and at 28 days after treatment
measure: Anxiety
timeFrame: At baseline, each day during treatment (3-5 Days on average), 7, 14, 28 days and 3, 6, and 12 months after treatment
measure: Depression
timeFrame: At baseline, each day during treatment (3-5 Days on average), 7, 14, 28 days and 3, 6, and 12 months after treatment
measure: Suicidal Ideation
timeFrame: At baseline, each day during treatment (3-5 Days on average), 7, 14, 28 days and 3, 6, and 12 months after treatment
measure: Post Traumatic Stress
timeFrame: Once during treatment
measure: Study Drug Side Effects
timeFrame: At baseline, each day during treatment (3-5 Days on average), 7, 14, 28 days and 3, 6, and 12 months after treatment
measure: Spirituality
timeFrame: Baseline, once during treatment, and at 28 days post treatment.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Faulkner Hospital
state: Massachusetts
Study officials:
References: