Pilot Study of Nicotine Nasal Spray and Varenicline on Smoking in Methadone-Maintained Patients

A Pilot Randomized, Placebo-Controlled, Crossover Study of the Effect of the Nicotine Nasal Spray and Varenicline on Cigarette Smoking Following Methadone Dosing in Methadone-Maintained Patients

The objective is to provide a preliminary test of the ability of two pharmacological treatments, the nicotine nasal spray and varenicline, relative to placebos, to reduce smoking during the 4 hours following methadone dosing.

Study Overview

• Status: Terminated
• Conditions: Cigarette Smoking; Methadone Maintenance
• Intervention / Treatment: Drug: Nicotine Nasal Spray; Drug: Varenicline; Drug: Placebo Nasal Spray; Drug: Placebo Varenicline

Detailed Description

Smoking prevalence is over 83% in methadone-maintained patients. These patients experience significant difficulty quitting, and there is evidence that a majority of methadone-maintained patients smoke most of their cigarettes in the 4 hours following methadone dosing. The objective is to provide a preliminary test of the ability of two pharmacological treatments, the nicotine nasal spray and varenicline, relative to placebos, to reduce smoking during the 4 hours following methadone dosing.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • UC Physicians Company, LLC Opioid Treatment Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. be male or female, 18 years of age or older
2. be able to understand the study, and having understood, provide written informed consent in English
3. have been enrolled in the University of Cincinnati Physicians Company-Opioid Treatment Program (UCPC-OTP) program for at least 30 days and be stable on the current methadone dose for at least 1 week
4. have smoked cigarettes for at least 3 months, have a measured exhaled carbon monoxide (CO) level > 8 parts per million (ppm), and not planning to seek smoking-cessation treatment within the next 3 months
5. have a willingness to comply with all study procedures, including trying to stop smoking during designated weeks, and to comply with medication instructions
6. based on a week of Quitbit cigarette lighter assessments, with at least 5 days of usable data, smoke ≥ 10 cigarettes/day and smoke at least 30% of daily cigarettes within the 4-hour post-methadone-dosing period
7. if female and of child bearing potential, agree to use one of the following methods of birth control: oral contraceptives, contraceptive patch, barrier (diaphragm or condom), intrauterine contraceptive system, levonorgestrel implant, medroxyprogesterone acetate contraceptive injection,complete abstinence from sexual intercourse, hormonal vaginal contraceptive ring.

Exclusion Criteria:

1. have a current or past diagnosis of any psychotic disorder, or bipolar I or II disorder
2. have a psychiatric condition that, in the judgment of the study physician would make study participation unsafe or which would make treatment compliance difficult
3. be a significant suicidal/homicidal risk

4. have a medical condition that, in the judgment of the study physician, would make study participation unsafe or which would make treatment compliance difficult. Such conditions include, but are not limited to:

   • liver function tests greater than 3 times upper limit of normal
   • serum creatinine greater than 2 mg/dL
5. have had clinically significant cardiovascular or cerebrovascular disease within the past 6 months or have clinically significant ECG abnormalities
6. have taken an investigational drug within 30 days before consent
7. be taking concomitant medications that are contraindicated for use with the NNS or varenicline
8. be taking any concomitant medications that could increase the likelihood of smoking cessation (such as wellbutrin or nortriptyline)
9. have a known or suspected hypersensitivity to varenicline or the nicotine nasal spray (NNS)
10. use/have used smoking-cessation counseling programs with individual counseling or smoking-cessation medication treatments currently, or within 30 days before consent
11. have used electronic cigarettes or tobacco products, other than cigarettes, in the week before consent
12. be pregnant or breastfeeding
13. be anyone who, in the judgment of the investigator, would not be expected to complete the study protocol (e.g., due to relocation from the clinic area, probable incarceration, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Order 1; Subjects assigned to this arm will receive Placebo Nasal Spray first (Week 1), followed by Nicotine Nasal Spray (Week 2), followed by Varenicline (Weeks 3-4), followed by a washout period (Week 5) and then Placebo Varenicline (Weeks 6-7).	Drug: Nicotine Nasal Spray; 7 days. 1 mg/dose, up to 40x/day.; Drug: Varenicline; 14 days. Days 1-3: 0.5 mg once daily; Days 4-7: 0.5 mg twice daily; Days 8-14: 1 mg twice daily.; Drug: Placebo Nasal Spray; 7 days. 1 mg/dose, up to 40x/day.1 mg/dose, up to 40x/day. This will appear similar to the Nicotine Nasal Spray, but will be a placebo.; Drug: Placebo Varenicline; 14 days. Days 1-3: 0.5 mg once daily; Days 4-7: 0.5 mg twice daily; Days 8-14: 1 mg twice daily. This will appear identical to the drug Varenicline, but will be a placebo.
EXPERIMENTAL: Order 2; Subjects assigned to this arm will receive Placebo Nasal Spray first (Week 1), followed by Nicotine Nasal Spray (Week 2), followed by Placebo Varenicline (Weeks 3-4), followed by a washout period (Week 5) and then Varenicline (Weeks 6-7).	Drug: Nicotine Nasal Spray; 7 days. 1 mg/dose, up to 40x/day.; Drug: Varenicline; 14 days. Days 1-3: 0.5 mg once daily; Days 4-7: 0.5 mg twice daily; Days 8-14: 1 mg twice daily.; Drug: Placebo Nasal Spray; 7 days. 1 mg/dose, up to 40x/day.1 mg/dose, up to 40x/day. This will appear similar to the Nicotine Nasal Spray, but will be a placebo.; Drug: Placebo Varenicline; 14 days. Days 1-3: 0.5 mg once daily; Days 4-7: 0.5 mg twice daily; Days 8-14: 1 mg twice daily. This will appear identical to the drug Varenicline, but will be a placebo.
EXPERIMENTAL: Order 3; Subjects assigned to this arm will receive Nicotine Nasal Spray first (Week 1), followed by Placebo Nasal Spray (Week 2), followed by Varenicline (Weeks 3-4), followed by a washout period (Week 5) and then Placebo Varenicline (Weeks 6-7).	Drug: Nicotine Nasal Spray; 7 days. 1 mg/dose, up to 40x/day.; Drug: Varenicline; 14 days. Days 1-3: 0.5 mg once daily; Days 4-7: 0.5 mg twice daily; Days 8-14: 1 mg twice daily.; Drug: Placebo Nasal Spray; 7 days. 1 mg/dose, up to 40x/day.1 mg/dose, up to 40x/day. This will appear similar to the Nicotine Nasal Spray, but will be a placebo.; Drug: Placebo Varenicline; 14 days. Days 1-3: 0.5 mg once daily; Days 4-7: 0.5 mg twice daily; Days 8-14: 1 mg twice daily. This will appear identical to the drug Varenicline, but will be a placebo.
EXPERIMENTAL: Order 4; Subjects assigned to this arm will receive Nicotine Nasal Spray first (Week 1), followed by Placebo Nasal Spray (Week 2), followed by Placebo Varenicline (Weeks 3-4), followed by a washout period (Week 5) and then Varenicline (Weeks 6-7).	Drug: Nicotine Nasal Spray; 7 days. 1 mg/dose, up to 40x/day.; Drug: Varenicline; 14 days. Days 1-3: 0.5 mg once daily; Days 4-7: 0.5 mg twice daily; Days 8-14: 1 mg twice daily.; Drug: Placebo Nasal Spray; 7 days. 1 mg/dose, up to 40x/day.1 mg/dose, up to 40x/day. This will appear similar to the Nicotine Nasal Spray, but will be a placebo.; Drug: Placebo Varenicline; 14 days. Days 1-3: 0.5 mg once daily; Days 4-7: 0.5 mg twice daily; Days 8-14: 1 mg twice daily. This will appear identical to the drug Varenicline, but will be a placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Daily Cigarettes Smoked in the 4 Hours After Receiving Methadone Dose	Subjects will be given a special electronic cigarette lighter called Quitbit.The electronic lighter will record a timestamp for each time the lighter is used to light a cigarette. Data will be collected from the lighter at each study visit. This will measure how many cigarettes are smoked and when.	7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cigarettes Per Day	The Quitbit lighter will measure how many cigarettes are smoked per day. In addition to the Quitbit lighter measurement, the Timeline Follow Back (TLFB) form will be filled out for each subject to measure use, as well.	7 weeks
Number of Participants With Carbon Monoxide Levels Less Than or Equal to 8 Parts-per-million	Carbon monoxide (CO) in each participant's breath will be tested. A CO level less than or equal to 8 parts-per-million will be used to verify reports of no smoking.	up to 8 weeks

Collaborators and Investigators

• Sponsor: University of Cincinnati

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (ACTUAL): August 25, 2017
• Study Completion (ACTUAL): August 25, 2017

Study Registration Dates

• First Submitted: May 19, 2014
• First Submitted That Met QC Criteria: May 21, 2014
• First Posted (ESTIMATE): May 26, 2014

Study Record Updates

• Last Update Posted (ACTUAL): December 5, 2018
• Last Update Submitted That Met QC Criteria: December 4, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Smoking; Methadone; Nicotine; Cigarette; Varenicline; Cessation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine; Varenicline
• Other Study ID Numbers: 2013-7275

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No