Mechanisms of Lorcaserin for Smoking Cessation

Smoking Cessation Clinical Trial

Official title:

Behavioral Mechanisms of Lorcaserin Treatment for Smoking Cessation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04396834
• Other study ID #: 04619
• Status: Terminated
• Phase: Phase 2
• Start date: December 4, 2019
• Est. completion date: February 26, 2020

Study information

• Verified date: March 2023
• Source: The Mind Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Identifying new medication options is critical for curbing the health burdens of cigarette smoking. Currently approved smoking cessation medications act on nicotinic receptors, and additional work is needed to identify medications with alternate pharmacological targets. Based on evidence that the serotonin system plays a role in nicotine consumption and relapse, this study will examine whether a selective serotonin medication alters smoking-related behaviors and responses to cigarette smoking under controlled conditions, informing its potential utility for smoking cessation.

Description:

Tobacco use remains the foremost cause of preventable deaths in the U.S. and worldwide. Advancing new smoking cessation therapies, including those with novel pharmacological targets, is a critical public health priority. The serotonin (5-hydroxtytryptamine; 5-HT) system is broadly implicated in the regulation of reward- related behavior, including drug seeking, in part reflecting its modulatory role in dopamine (DA) function. Recent studies show that targeted manipulation of the serotonin 5-HT2C receptor alters drug-related behavior; in particular, 5-HT2C receptor agonists are shown to reduce nicotine intake and reinstatement. Of the selective 5-HT2C receptor agonists, lorcaserin has the best near-term potential for repurposing as a smoking cessation therapy, having been approved by the U.S. Food and Drug Administration for weight management.

Preclinical findings implicate several potential behavioral mechanisms by which 5-HT2C receptor agonists might reduce drug intake, including drug-specific processes (e.g., incentive salience of drug cues, self-administration, reinstatement) and drug-nonspecific behaviors (e.g., reductions in impulsivity). To date, potential mechanisms of 5-HT2C receptor agonists have not been characterized in human studies. Given emerging interest in lorcaserin as a novel smoking cessation therapy, further studies are needed to evaluate its efficacy profile, including studies to evaluate candidate treatment mechanisms. This human laboratory investigation will examine the effects of lorcaserin vs. placebo on relapse-related outcomes using a double-blind, within-subjects, crossover design. Impulsivity subdomains will also be examined as candidate mechanisms for medication effects. By evaluating an approved 5-HT2C agonist with emergent efficacy for smoking cessation, this project has near-term potential to inform clinical applications of 5-HT2C agonists for addiction.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: February 26, 2020
• Est. primary completion date: February 26, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. age 18-65

2. smoking 5+ cigarettes per day (average) over the past year, with no period of abstinence > 90 days

3. biochemical verification of smoking status

4. at least low to moderate nicotine dependence

5. reporting long-term motivation to quit smoking

6. willingness to take study pills and complete study procedures

7. willingness to complete lab sessions involving cigarette smoking

Exclusion Criteria:

1. meeting DSM-5 criteria for substance use disorder aside from tobacco use disorder and mild cannabis use disorder

2. recent (30 day) illicit drug use (except marijuana), based on self-report and urine drug screen

3. past 30-day use of tobacco cessation aids or nicotine/tobacco products other than cigarettes

4. past 30-day use of SSRIs, other psychiatric medications, or weight control medications

5. lifetime diagnosis of severe mental illness (e.g., psychotic or bipolar I disorder)

6. significant medical or neurological illness, including severe hepatic impairment or cirrhosis, or insulin dependent diabetes

7. actively engaged in smoking cessation treatments or a smoking cessation attempt (or intent to start an attempt in the next 90 days)

8. interested in quitting smoking immediately (i.e., in the next two months)

9. Medications contraindicated for use with lorcaserin or which have a significant interaction with lorcaserin

10. body mass index (BMI) under normal range (BMI < 18 kg/m2)

11. history of significant cardiovascular conditions including history of arrhythmias or heart block, heart failure, valvular heart disease, heart attack, stroke, unstable angina

12. abnormal electrocardiogram (ECG) results

13. nursing, pregnant, or anticipating pregnancy

14. history of suicide attempt or recent 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

Related Conditions & MeSH terms

• Smoking Cessation
• Tobacco Use Disorder

Intervention

Drug:
• Lorcaserin Oral Tablet
Lorcasering 10mg Oral Tablet (BID)
• Placebo oral tablet
Placebo Oral Tablet (BID)

Locations

Country	Name	City	State
United States	The Mind Research Network	Albuquerque	New Mexico

Sponsors (1)

Lead Sponsor	Collaborator
The Mind Research Network

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Smoking Lapse	Duration (in minutes) until lapsing to smoking during a 50-minute period	Laboratory session following 7 days of medication or placebo pills
Primary	Laboratory Cigarette Smoking	Number of cigarettes consumed during a 60-minute period	Laboratory session following 7 days of medication or placebo pills
Secondary	Impulsivity	Performance on a behavioral measure of impulsivity, the stop signal task. Reported is the stop signal reaction time, the number of milliseconds required to activate the "stop" process in the stop signal task.	Laboratory session following 7 days of medication or placebo pills.
Secondary	Reward Sensitivity	Performance on a behavioral measure of reward sensitivity (response bias measure on a signal detection task). Response bias is computed by the following equation: 1/2 * log((# correct stim 1 * # incorrect stim 2)/(# incorrect stim 1 * # correct stim 2)); Stimulus 1 is associated with a higher proportion of correct feedback than Stimulus 2, and by computing the ratio above, we are able to determine the response bias of the participant. The response bias measure provides an objective measure of reward sensitivity (i.e., the degree to which participants are biased towards choosing the more frequently rewarded response).	Laboratory session following 7 days of medication or placebo pills.
Secondary	Daily Cigarette Smoking	Cigarettes smoked per day	During 7 days of medication or during 7 days of placebo pills (difference score between weeks).