Clinical trial NCT02906644: Combination Nicotine Patch / Lorcaserin for Smoking Cessation
Official title: Combination Nicotine Patch / Lorcaserin for Smoking Cessation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nicotine Dependence
Keywords: Nicotine addiction
Cigarette smoking
Smoking cessation
lorcaserin
Belviq
Nicotine patches
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2016-09-20
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study plans to compare the efficacy of the nicotine patch / lorcaserin combination treatment vs. the nicotine patch alone in terms of leading to a reduction in smoking behavior and withdrawal symptoms.

Detailed description: This study proposes to investigate the potential efficacy of a combination of two FDA-approved agents, nicotine patch and lorcaserin, for smoking cessation treatment. The nicotine patch which provides a sustained low dose of nicotine is a nicotine receptor agonist. Lorcaserin, a serotonin 5-hydroxytryptamine receptor 2C (5-HT2C) agonist, is a drug that is FDA-approved for weight loss, and has also recently been shown to be efficacious for smoking cessation. Given that these drugs act through distinct mechanisms it is hoped that the combination will prove more efficacious than either drug alone. It is also hypothesized that the combination will reduce weight gain commonly seen after smoking cessation.

Eligibility criteria: Inclusion Criteria:

* 18-65 years old;
* Smoke an average of at least 10 cigarettes per day;
* Have smoked at least one cumulative year;
* Have an expired air CO reading of at least 10ppm;
* Body weight of \>50 kg (110 lbs.)
* Able to read and understand English;
* Express a desire to quit smoking in the next thirty days.

Exclusion Criteria:

* Hypertension (systolic \>140 mm Hg, diastolic \>100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100.
* Hypotension with symptoms (systolic \<90 mm Hg, diastolic \<60 mm Hg).
* Participants with a history of hypertension may, however, be allowed to participate in the study if the study physician or physician assistant determines that the condition is stable, controlled by medication, and in no way jeopardizes the individual's safety.
* Coronary heart disease, diagnosed by coronary angiogram;
* Lifetime history of heart attack;
* Cardiac rhythm disorder (irregular heart rhythm);
* Chest pain in the last month (unless history, exam, and ECG clearly indicate a non-cardiac source);
* Symptomatic cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure);
* Diagnosis of liver disease or kidney disorder (except kidney stones, gallstones);
* Gastrointestinal problems (e.g. Celiac disease, Crohn's dx Ulcerative Colitis) or disease other than gastroesophageal reflux or heartburn;
* Active ulcers in the past 30 days;
* Currently symptomatic lung disorder/disease (including but not limited to chronic obstructive pulmonary disease (COPD), emphysema, and asthma);
* Brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder);
* Migraine headaches that occur more frequently than once per week;
* Recent, unexplained fainting spells;
* Problems giving blood samples;
* Diabetes (unless controlled by diet and exercise alone and screening glucose is less than 180mg/dcl and HbA1c is less than 7%);
* Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer);
* HIV, Hepatitis B, or Hepatitis C
* History of tuberculosis or recent positive purified protein derivative (PPD) test
* Other major medical condition;
* Current psychiatric disease (with the exception of anxiety disorders, obsessive compulsive disorder (OCD) and ADHD);
* Suicidal ideating (thinking about ways to commit suicide) (within the past 10 years) or lifetime occurrence of attempted suicide;
* Current depression - The Patient Health Questionnaire (PHQ-9) for Depression will be used to screen for current (within 2 weeks) depression. Potential subjects who score \>9 (or who score \>0 on item #9 ("Thoughts that you would be better off dead, or of hurting yourself in some way") will be excluded from study participation, and, at the discretion of the study physician, referred to appropriate psychiatric treatment;
* Bulimia or anorexia;
* BMI of \< 18.5 kg/m2;
* Prior use of fenfluramine or dexfenfluramine
* Use (within the past 30 days) of:

  * Illegal drugs (or if the urine drug screen is positive for tetrahydrocannabinol (THC), Cocaine, Amphetamine, Opiates, Methamphetamines, phencyclidine (PCP), Benzodiazepines, or Barbiturates), Unless recent use of prescription Opiates, Benzodiazepines for management of acute symptoms.
  * Experimental (investigational) drugs;
  * Psychiatric medications including antidepressants (selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), St. John's Wort), lithium, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine);
  * Phentermine, triptans, tryptophan, linezolid, dextromethorphan, opiates, tramadol, or dopamine agonists;
  * Any agents that have documented correlation with increased incidence of valvulopathy and/or pulmonary hypertension (e.g., cyproheptadine, trazodone, nefazodone, amoxapine, tricyclic antidepressants, mirtazapine, pergolide, ergotamine, methysergide) (or anticipated use during the study);
  * Smokeless tobacco (chewing tobacco, snuff), pipes or e-cigarettes;
  * Wellbutrin, bupropion, Zyban, Chantix, varenicline, nicotine patch, nicotine replacement therapy or any other smoking cessation aid.
* Concurrent use of a serotonergic agent/combination associated with severe serotonin syndrome (within the past 30 days);
* Use of cigar, cigarillos, pipe, Hookah, dissolvable nicotine, snuff, chewing tobacco more than once per month.
* Use of e-cigarettes once per month or more.
* Self-report of consuming 4 or more alcoholic drinks on 1 or more days per week;
* Significant adverse reaction to lorcaserin or nicotine patch in the past.
* Current participation or recent participation (in the past 30 days) in another smoking study at the investigators Center or another research facility.
* Current participation in another research study.

Primary outcomes:
measure: Time-to-lapse
timeFrame: Week 2 pre quit day
measure: Smoking Withdrawal
timeFrame: Week 2 pre quit day
Secondary outcomes:
measure: Number of Participants Reporting Smoking Abstinence
timeFrame: Weeks 7-10 post quit day
measure: Number of Participants Reporting Tolerability Issues With Lorcaserin + Nicotine Patch Treatment
timeFrame: Two Weeks pre and 10 weeks post quit day
measure: Weight Gain Following Continuous Four-week Abstinence From Smoking
timeFrame: Week 10 post quit day
measure: Number of Participants Reporting 6-month Smoking Abstinence
timeFrame: 6 months post Quit Day
measure: Percentage of Change in Ad Libitum Smoking at End of Week 2
timeFrame: Week 2 pre quit day
measure: Adherence to Lorcaserin + Nicotine Patch Treatment as Indicator of Tolerability
timeFrame: Two Weeks pre and 10 weeks post quit day
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Center for Smoking Cessation
state: North Carolina
Study officials:
affiliation: Duke University
name: Jed E. Rose, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hartmann-Boyce J, Theodoulou A, Farley A, Hajek P, Lycett D, Jones LL, Kudlek L, Heath L, Hajizadeh A, Schenkels M, Aveyard P. Interventions for preventing weight gain after smoking cessation. Cochrane Database Syst Rev. 2021 Oct 6;10(10):CD006219. doi: 10.1002/14651858.CD006219.pub4.
citation: Rose JE, Davis JM. Combination Lorcaserin and Nicotine Patch for Smoking Cessation Without Weight Gain. Nicotine Tob Res. 2020 Aug 24;22(9):1627-1631. doi: 10.1093/ntr/ntz149.