Clinical trial NCT04396847: Laboratory Screening of Lorcaserin for Alcohol Use Disorder
Official title: Human Laboratory Screening of Lorcaserin in Smokers With Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Alcohol Use Disorder
Tobacco Smoking
Lead sponsor: The Mind Research Network
Sponsor class: OTHER
First posted: 2020-05-21
Enrollment: 5
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Heavy-drinking smokers, including those with alcohol use disorder (AUD), are at increased risk for numerous negative health outcomes relative to those who use alcohol or cigarettes only. Although heavy-drinking smokers are recognized as an important subgroup for clinical and public health interventions, there are presently no approved medications for the joint indication of alcohol reduction and smoking cessation. Based on evidence that the serotonin system plays a role in alcohol and nicotine consumption and relapse, this study aims to examine whether a serotonin medication alters alcohol and nicotine responses in smokers with AUD, informing its potential utility as a candidate therapy for this clinical subgroup.

Detailed description: Pharmacotherapy development remains a critical objective for reducing health and societal burdens associated with alcohol use disorder (AUD). Developing targeted treatments for specific AUD subgroups is a key objective. Among those with AUD, cigarette smokers comprise a sizable and critical subgroup with disproportionally high long-term health risks, making it a key priority to advance therapies for concurrent AUD and cigarette smoking. The serotonin (5-hydroxtytryptamine; 5-HT) system is broadly implicated in addictive behaviors, in part reflecting the role of 5-HT in modulating dopamine function. Preclinical studies of 5-HT receptor drugs have shown that targeted modulation of the 5-HT2C receptor (implicated in 5-HT-related inhibition of DA function) alters the consumption and reinstatement of addictive drugs, including alcohol and nicotine. Of the selective 5-HT2C receptor agonists, lorcaserin has superior near-term potential for repurposing as an AUD therapy, having been approved by the Food and Drug Administration for weight management. Human laboratory medication trials offer a time- and cost-effective option for validating preclinical findings prior to larger randomized controlled trials, and for testing candidate treatment mechanisms. This Phase II human laboratory screening trial will evaluate lorcaserin as a novel candidate therapy for smokers with AUD. Effects of lorcaserin vs. placebo will be evaluated in a double-blind, within-subjects, crossover study with human laboratory endpoints. This study will provide early human data on the effects of a 5-HT2C receptor agonist in relation to alcohol-related outcomes, informing its potential for further evaluation as a candidate treatment for AUD.

Eligibility criteria: Inclusion Criteria:

1. Age 21-65
2. Meeting DSM-5 criteria for current (past year) AUD, as well as current at-risk drinking (i.e., ≥14/21 drinks per week for women/men, on average), with at least four episodes of 4+/5+ drinks in the past 30 days
3. Daily smoker, defined as reporting smoking 1+ cigarettes per day, on average, over the past 12 months
4. Willingness to take study pills and complete study procedures
5. Willingness to complete lab sessions involving alcohol administration

Exclusion Criteria:

1. Recent (30 day) illicit drug use (with the exception of cannabis) based on self-report or toxicology screen
2. Meeting DSM-5 criteria for a past-year substance use disorder other than alcohol use disorder, tobacco use disorder, or mild cannabis use disorder
3. Significant alcohol withdrawal, based on a Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) score of 8+ at baseline medical visit, or any reported history of severe withdrawal symptoms (e.g., seizures)
4. Past 30-day use of nicotine replacement
5. Past 30-day use of SSRIs, other psychiatric medications, or weight control medications
6. Lifetime diagnosis of severe mental illness (e.g., psychotic or bipolar I disorder)
7. Significant medical or neurological illness based on medical staff (i.e., physician or nurse practitioner) evaluation including severe hepatic impairment or cirrhosis, insulin dependent diabetes
8. Current alcohol or smoking cessation treatment or efforts to cut down on drinking/smoking
9. Medications contraindicated for use with lorcaserin or which have a significant interaction with lorcaserin
10. Body mass index (BMI) under normal range (\<18kg/m2)
11. History of significant cardiovascular conditions including history of arrhythmias or heart block, heart failure, valvular heart disease, heat attack, stroke, unstable angina
12. Abnormal electrocardiogram (ECG) results
13. Currently nursing, pregnant, or anticipating pregnancy
14. history of suicide attempt or recent suicidal ideation (i.e., Suicidal thoughts (intent or plan) in the last month)
15. Plans to travel outside of the local area during the study period, or inability to commit to entire duration of study

Primary outcomes:
measure: Laboratory Alcohol Consumption
timeFrame: Laboratory session following 7 days of medication or laboratory session following 7 days of placebo pills.
Secondary outcomes:
measure: Subjective Responses to Alcohol
timeFrame: Laboratory session following 7 days of medication or laboratory session following 7 days of placebo pills
measure: Motivation to Consume Alcohol
timeFrame: Laboratory session following 7 days of medication or laboratory session following 7 days of placebo pills.
measure: Motivation to Smoke Cigarettes
timeFrame: Laboratory session following 7 days of medication or laboratory session following 7 days of placebo pills.
measure: Daily Alcohol Consumption
timeFrame: During 7 days of medication or during 7 days of placebo pills.
measure: Cigarette Consumption
timeFrame: During 7 days of medication or during 7 days of placebo pills.
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: The Mind Research Network
state: New Mexico
Study officials:
affiliation: The Mind Research Network
name: Christian Hendershot, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Mind Research Network
name: Eric Claus, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: