Deep rTMS and Varenicline for Smoking Cessation

Deep rTMS and Varenicline for Smoking Cessation: A Pilot Study Exploring the Efficacy of a Combined Treatment Approach

The purpose of this study is to investigate the effect of deep repetitive transcranial magnetic stimulation (rTMS) using the insula H-coil on smoking outcomes in smokers receiving varenicline. It is hypothesized that active deep rTMS will improve abstinence rates, attenuate craving and reduce cigarette consumption and dependence severity.

Study Overview

• Status: Active, not recruiting
• Conditions: Smoking Cessation; Tobacco Use Disorder
• Intervention / Treatment: Device: Deep Repetitive Transcranial Magnetic Stimulation (Active); Drug: Varenicline; Device: Deep Repetitive Transcranial Magnetic Stimulation (Sham)

Detailed Description

This study will be a randomized, double-blind, sham-controlled clinical trial. Nicotine dependent participants will be recruited and randomized tor receive either active or sham rTMS intervention for 4 weeks (5 sessions/week). All participants will receive an open-label treatment of varenicline for 12 weeks and weekly counselling sessions. The aims of the study are:

1. To examine the efficacy of bilateral deep rTMS to the insula on point prevalence smoking abstinence in smokers receiving varenicline treatment.
2. To examine the efficacy of bilateral deep rTMS to the insula on other smoking outcomes such as craving, cigarette smoking and dependence severity.
3. To examine the effect of bilateral deep rTMS to the insula on abstinence at the end of rTMS treatment and at 6-month follow up.

Abstinence will be measured by point prevalence at week 4 and 12 and prolonged continuous abstinence at week 26. This will be confirmed using plasma cotinine levels. All other measures will be done using various questionnaires such as Fagerstrom Test of Nicotine Dependence (FTND), Timeline Follow-Back (TLFB), Minnesota Nicotine Withdrawal Scale (MNWS), and Tiffany Questionnaire of Smoking Urges (T-QSU).

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5S 2S1
      • Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-65;
• Nicotine dependent as assessed by Diagnostic and Statistical Manual of Mental Disorders (DSM-V);
• Reported daily cigarette consumption ≥ 10 and expired carbon monoxide (CO) measurement of ≥ 10 ppm;
• Fagerstrom Test of Nicotine Dependence (FTND) ≥ 4;
• Reported motivation to quit within 30 days as assessed using the Contemplation Ladder score of ≥ 7.

Exclusion Criteria:

• Reported smoking abstinence in the 3 months preceding screening visit;
• Current use of other smoking cessation aids;
• Allergy and/or contraindication to varenicline or rTMS;
• Pregnancy, trying to become pregnant or breastfeeding;
• Current or recent history of cardiovascular or cerebrovascular disease and/or current hypertension;
• Current or historical evidence of suicidal behavior;
• Serious current or personal history of medical condition/disease (neurological disorders, brain lesions, multiple sclerosis, head trauma, loss of consciousness, hearing loss, etc.);
• Current, personal history or family history of seizures;
• Cognitive impairment as defined as a Mini Mental State Examination (MMSE) score <24;
• Concomitant use of medication that lowers seizure threshold

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Deep rTMS active + Varenicline; Participants undergoing deep rTMS (active) for 4 weeks (5 sessions/week) along with 12 weeks of varenicline.	Device: Deep Repetitive Transcranial Magnetic Stimulation (Active); Active deep rTMS (10 Hz) using the H-coil to target the bilateral insula; Drug: Varenicline; 12 week course treatment of varenicline (0.5 mg/1 mg) using the standard dosage schedule for smoking cessation (Day 1-3: 0.5 mg daily; day 4-7: 0.5 mg twice a day; day 8-end of treatment: 1 mg twice a day).; Other Names: Champix
SHAM_COMPARATOR: Deep rTMS sham + Varenicline; Participants undergoing deep rTMS (sham) for 4 weeks (5 sessions/week) along with 12 weeks of varenicline.	Drug: Varenicline; 12 week course treatment of varenicline (0.5 mg/1 mg) using the standard dosage schedule for smoking cessation (Day 1-3: 0.5 mg daily; day 4-7: 0.5 mg twice a day; day 8-end of treatment: 1 mg twice a day).; Other Names: Champix; Device: Deep Repetitive Transcranial Magnetic Stimulation (Sham); Sham deep rTMS using the H-coil. The sham coil is built into the same helmet as the active coil. It mimics the active coil with regards to acoustics and scalp sensations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Point prevalence abstinence at the end of 12 weeks	Measured by self-report of smoking abstinence in the past 7 days and confirmed using plasma cotinine measurement.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fagerstrom Test For Nicotine Dependence (FTND) score	This will be used to assess physical dependence severity in participants. It is a 6 item scale and total scores can range from 0-10. A higher score indicates more severe nicotine dependence.	26 weeks
Expired CO Measurements	This will be used as a biological confirmation of recent smoking.	26 weeks
Cigarettes per day (TLFB)	Self-reported measure of cigarette consumption.	26 weeks
Minnesota Nicotine Withdrawal Scale (MNWS) score	This will be used to assess withdrawal symptoms. It is an 8 item scale and total scores range from 0 to 24. A higher score indicates more severe nicotine withdrawal.	26 weeks
Tiffany Questionnaire for Smoking Urges (T-QSU) score	This will be used to assess symptoms of craving/urges for tobacco. It is a 32 item scale and total scores range from 0 to 224. A higher score indicates more severe smoking craving/urges.	26 weeks
Point prevalence abstinence at the end of 4 weeks	Measured by self-report of smoking abstinence in the past 7 days and confirmed using plasma cotinine measurement.	4 weeks
Prolonged abstinence from end of treatment (Week 12) to end of follow up (Week 26)	Measured by self-report of smoking abstinence since the last visit and confirmed using plasma cotinine measurement.	26 weeks
Prolonged abstinence with 2-week grace period at end of follow up (Week 26)	Measured by self-report of smoking abstinence since the last visit and confirmed using plasma cotinine measurement.	26 weeks
Continuous abstinence at 6 months	Measured by self-report of smoking abstinence since the last visit and confirmed using plasma cotinine measurement.	26 weeks

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Collaborators: Pfizer; Brainsway
• Investigators: PRINCIPAL_INVESTIGATOR: Bernard Le Foll, MD,PhD,MCFP, Centre for Addiction and Mental Health

Publications and helpful links

General Publications

• Ibrahim C, Malik S, Barr MS, Blumberger DM, Daskalakis ZJ, Le Foll B. Insula deep rTMS and varenicline for smoking cessation: A randomized control trial study protocol. Front Pharmacol. 2022 Sep 8;13:969500. doi: 10.3389/fphar.2022.969500. eCollection 2022.

Helpful Links

• Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 22, 2019
• Primary Completion (ACTUAL): September 13, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: September 6, 2019
• First Submitted That Met QC Criteria: September 6, 2019
• First Posted (ACTUAL): September 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: addiction; smoking cessation; varenicline; insula; tobacco use disorder; deep rTMS
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: 051/2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No