Nicotine Replacement Therapy (NRT) and Bupropion Mechanisms of Effectiveness in Smokers

NCT01048944 | Completed Phase 4 Results DMC

• 2 other identifiers: NIH/NIDA-2R01DA0122892R01DA012289
• Study Type: interventional
• Target: 197
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to better characterize differences in mood, attention, brain activation patterns underlying the beneficial effects of pharmacological treatments previously demonstrated to be help individuals successfully quit tobacco smoking. Smokers will be randomly assigned to one of three treatments: 1) bupropion sustained release (SR), 2) nicotine patch, or 3) placebo patches plus pills across a 45-day period with a 3-week intensive post-treatment follow-up. In addition, 20 percent of the subjects will be randomized to a delayed-quit control group.

Conditions

Nicotine Dependence

Keywords

Electroencephalography; nicotine; bupropion; attention; drug withdrawal symptoms

Outcome Measures

Primary Outcomes (2)

• Changes in Log Brain-wave (EEG) Activity (Power [Microvolts Squared]) From Pre-quit Baseline to 66 Days Post-quit, Assessed at 3, 24, 45, and 66 Days Post-quit.

  Brain-wave activity (EEG) was assessed using electrodes on the subject's scalp, the outputs of which were and quantified by a commercial brain wave machine. EEG was collected at frontal (e.g., Fz) and parietal (e.g., Pz) electrodes while subjects relaxed. EEG was analyzed using computer programs that measured slow-frequency EEG waves known as delta (1.5-4.5 cycles/second \[cps\]), theta-1 (4.5-6.0 cps), theta-2 (6.0-7.7 cps), and alpha-1 (7.8-10.0 cps), and higher frequency waves. Generally, delta, alpha-1 and theta waves reflect deactivation of the brain activity, while higher frequency waves reflect greater brain activation. Brain activity was quantified as the natural log of EEG power \[microvolts squared\] as determined by the fast Fourier mathematical algorithm. Days post quit were components of Time. The primary focus was on changes in the individual subject's log theta-1, theta-2, and alpha-1 power at post-quit points in time minus the log values at the pre-quite baseline.

  Mean EEG power [microvolts squared] from at baseline, 3, 24, 45, and 66 days post-quit

• Changes in Log of Smoking Withdrawal Scores (Mood, and Depressive Symptoms) From Baseline Across 66 Days of Abstinence

  Changes in log from baseline in the widely used Shiffman-Jarvik Withdrawal "craving" and "psychological symptom" scores through 66 days of abstinence. Post-quit changes were assessed at days 3, 24, 45, and 66 of abstinence. The maximal range of value raw for craving is from "5" = (no craving) to "47" (maximally strong craving), while that for psychological symptoms is from "5" (no symptoms) to "60" (maximally intense symptoms of across multiple symptoms). Because the subtraction of logs is equivalent to the ratio of the two scores, a difference in logs (base 10) with a value of "1" is equal to an increase by a factor of 10, while a value of "0" is no change, and values of less than "0" are decreases below baseline values.

  Changes in log withdrawal symptoms from baseline through 66 days of abstinence

Study Arms (4)

Bupropion SR

ACTIVE COMPARATOR

150 mg bid bupropion SR

Drug: Bupropion SR

Nicotine Patch

ACTIVE COMPARATOR

21mg, 14mg, 7mg

Drug: Nicotine Patch

Placebo Patch and Placebo Pill

PLACEBO COMPARATOR

Individuals were placed on both a placebo patch that were the same size as active patches given to the Nicotine Patch group and were also given placebo pills were the same size and identically packaged as the active pills (bupropion) given to the Bupropion SR group.

Drug: Placebo Patch and Placebo Pill

Delayed-quit control

NO INTERVENTION

Smoke for 67 days while others have quit, then quit.

Interventions

Bupropion SR DRUG

150 encapsulated pill,3 days 1x/day then 56/day for 2x/day, then 3 day 1x/day ramp-down.

Also known as: ZybanSR

Bupropion SR

Nicotine Patch DRUG

Nicotine patch beginning 1st day cessation: 21 mg/24 days, 14 mg/14 days, 7 mg/7 days

Also known as: NicodermCQ

Nicotine Patch

Placebo Patch and Placebo Pill DRUG

150 encapsulated placebo pill,3 days 1x/day then 56/day for 2x/day, then 3 day 1x/day ramp-down. Placebo patch beginning 1st day cessation: 21 mg/24 days, 14 mg/14 days, 7 mg/7 days. The placebo patches were given beginning 1st day cessation: 21 mg size (but actually placebo)/24 days, 14 mg size (actually placebo)/ 14 mg size (actually placebo) 14 days/, 7 mg size (actually placebo)/7 days

Also known as: Placebo

Placebo Patch and Placebo Pill

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV) diagnosis of nicotine dependence with psychological dependence
• Smokes at least 10 cigarettes per day for the three months prior to enrollment
• Currently seeking treatment for nicotine dependence
• Medically healthy on the basis of physical examination and medical history, vital signs,
• Females must use an effective method of contraception for the duration of the study

You may not qualify if:

• DSM-IV diagnosis of abuse or dependence on alcohol or drugs other than nicotine
• Current Axis I diagnosis or current treatment with psychotropic medications within the three months prior to enrollment
• History of schizophrenia or other psychotic disorders, bipolar disorder, or anxiety disorders
• Currently seeking treatment for nicotine disorders
• History of seizures or head trauma with loss of consciousness, brain contusion, or fracture
• History of significant recent violent behavior
• Blood pressure greater than 150/90
• History of eating disorders
• History of allergic reaction to any of the study medications
• Pregnant

Sponsors & Collaborators

• Southern Illinois University Carbondale: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Southern Illinois University

Carbondale, Illinois, 62901-6502, United States

Location

Related Publications (1)

• Gilbert DG, Rabinovich NE, Gilbert-Matuskowitz EA, Klein KP, Pergadia ML. Smoking abstinence symptoms across 67 days compared with randomized controls-Moderation by nicotine replacement therapy, bupropion, and negative-affect traits. Exp Clin Psychopharmacol. 2019 Dec;27(6):536-551. doi: 10.1037/pha0000278. Epub 2019 Mar 28.

  PMID: 30920255 DERIVED

MeSH Terms

Conditions

Tobacco Use Disorder; Substance Withdrawal Syndrome

Interventions

Tobacco Use Cessation Devices

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Therapeutics

Limitations and Caveats

The modest sample size limited the ability to detect more subtle treatment effects. The exclusionary criteria limits generalization to excluded groups.

Results Point of Contact

• Title: David G. Gilbert, Ph.D.
• Organization: Southern Illinois University Carbondale

dgilbert@siu.edu

618-45303558

Study Officials

• David G Gilbert, PhD

  Southern Illinois University Carbondale

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychology

Study Record Dates

• First Submitted: January 13, 2010
• First Posted: January 14, 2010
• Study Start: June 1, 2005
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: November 25, 2014
• Results First Posted: November 25, 2014

Record last verified: 2014-11

Locations

US (1)