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

NCT ID: NCT02147132

Last Updated: 2018-12-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2017-08-25

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.

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.

Conditions

Cigarette Smoking; Methadone Maintenance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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).

Group Type: EXPERIMENTAL

Nicotine Nasal Spray

Intervention Type: DRUG

7 days. 1 mg/dose, up to 40x/day.

Varenicline

Intervention Type: DRUG

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.

Placebo Nasal Spray

Intervention Type: DRUG

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.

Placebo Varenicline

Intervention Type: DRUG

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.

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).

Group Type: EXPERIMENTAL

Nicotine Nasal Spray

Intervention Type: DRUG

7 days. 1 mg/dose, up to 40x/day.

Varenicline

Intervention Type: DRUG

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.

Placebo Nasal Spray

Intervention Type: DRUG

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.

Placebo Varenicline

Intervention Type: DRUG

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.

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).

Group Type: EXPERIMENTAL

Nicotine Nasal Spray

Intervention Type: DRUG

7 days. 1 mg/dose, up to 40x/day.

Varenicline

Intervention Type: DRUG

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.

Placebo Nasal Spray

Intervention Type: DRUG

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.

Placebo Varenicline

Intervention Type: DRUG

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.

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).

Group Type: EXPERIMENTAL

Nicotine Nasal Spray

Intervention Type: DRUG

7 days. 1 mg/dose, up to 40x/day.

Varenicline

Intervention Type: DRUG

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.

Placebo Nasal Spray

Intervention Type: DRUG

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.

Placebo Varenicline

Intervention Type: DRUG

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.

Interventions

Nicotine Nasal Spray

7 days. 1 mg/dose, up to 40x/day.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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.)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Theresa Winhusen

Ph.D

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Theresa Winhusen, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

UC Physicians Company, LLC Opioid Treatment Program

Cincinnati, Ohio, United States

Countries

United States

References

Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.

Reference Type: DERIVED

PMID: 37142273 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2013-7275

Identifier Type: -

Identifier Source: org_study_id