Mechanisms of Lorcaserin for Smoking Cessation

NCT ID: NCT04396834

Last Updated: 2023-03-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-04
• Study Completion Date: 2020-02-26

Brief 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.

Detailed 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.

Conditions

Tobacco Use Disorder; Smoking Cessation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Lorcaserin first, then placebo

Participants first receive lorcaserin (10 mg BID) for 7 days. After a washout period of 7 days, they then receive placebo tablets (BID) for 7 days.

Group Type: EXPERIMENTAL

Lorcaserin Oral Tablet

Intervention Type: DRUG

Lorcasering 10mg Oral Tablet (BID)

Placebo first, then lorcaserin

Participants first receive placebo (BID) for 7 days. After a washout period of 7 days, they then receive lorcaserin (10 mg BID) for 7 days.

Group Type: EXPERIMENTAL

Placebo oral tablet

Intervention Type: DRUG

Placebo Oral Tablet (BID)

Interventions

Lorcaserin Oral Tablet

Lorcasering 10mg Oral Tablet (BID)

Intervention Type: DRUG

Placebo oral tablet

Placebo Oral Tablet (BID)

Intervention Type: DRUG

Other Intervention Names

Belviq; Placebo pill

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Mind Research Network

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Hendershot, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

The Mind Research Network

Eric Claus, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

The Mind Research Network

Locations

The Mind Research Network

Albuquerque, New Mexico, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

04619

Identifier Type: -

Identifier Source: org_study_id