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

• ClinicalTrials.gov Identifier: NCT02147132
• Recruitment Status: Terminated
• First Posted: May 26, 2014
• Results First Posted: December 5, 2018
• Last Update Posted: December 5, 2018
• Sponsor: University of Cincinnati
• Information provided by (Responsible Party): Theresa Winhusen, University of Cincinnati

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cigarette Smoking; Methadone Maintenance	Drug: Nicotine Nasal Spray; Drug: Varenicline; Drug: Placebo Nasal Spray; Drug: Placebo Varenicline	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: March 2016
• Actual Primary Completion Date: August 25, 2017
• Actual Study Completion Date: August 25, 2017

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Proportion of Daily Cigarettes Smoked in the 4 Hours After Receiving Methadone Dose [ Time Frame: 7 weeks ]
   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.

Secondary Outcome Measures :

1. Cigarettes Per Day [ Time Frame: 7 weeks ]
   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.
2. Number of Participants With Carbon Monoxide Levels Less Than or Equal to 8 Parts-per-million [ Time Frame: up to 8 weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.)

Contacts and Locations

Locations

United States, Ohio

UC Physicians Company, LLC Opioid Treatment Program

Cincinnati, Ohio, United States, 45229

Sponsors and Collaborators

University of Cincinnati

Investigators

• Principal Investigator: Theresa Winhusen, PhD; University of Cincinnati

  Study Documents (Full-Text)

Documents provided by Theresa Winhusen, University of Cincinnati:

Study Protocol and Statistical Analysis Plan  [PDF] February 17, 2017

More Information

• Responsible Party: Theresa Winhusen, Ph.D, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT02147132
• Other Study ID Numbers: 2013-7275
• First Posted: May 26, 2014
• Results First Posted: December 5, 2018
• Last Update Posted: December 5, 2018
• Last Verified: December 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Theresa Winhusen, University of Cincinnati:

Cigarette; Methadone; Smoking; Cessation; Varenicline; Nicotine

Additional relevant MeSH terms:

Nicotine; Varenicline; Ganglionic Stimulants; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action