Clinical trial NCT04083144: Deep rTMS and Varenicline for Smoking Cessation
Official title: Deep rTMS and Varenicline for Smoking Cessation: A Pilot Study Exploring the Efficacy of a Combined Treatment Approach
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tobacco Use Disorder
Smoking Cessation
Keywords: smoking cessation
varenicline
deep rTMS
insula
addiction
tobacco use disorder
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Brainsway
First posted: 2019-09-10
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Point Prevalence Abstinence at the End of 12 Weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Fagerstrom Test For Nicotine Dependence (FTND) Score
timeFrame: 26 weeks
measure: Expired CO Measurements
timeFrame: 26 weeks
measure: Cigarettes Per Day (TLFB)
timeFrame: 26 weeks
measure: Minnesota Nicotine Withdrawal Scale (MNWS) Score
timeFrame: 26 weeks
measure: Tiffany Questionnaire for Smoking Urges (T-QSU) Score
timeFrame: 26 weeks
measure: Point Prevalence Abstinence at the End of 4 Weeks
timeFrame: 4 weeks
measure: Prolonged Abstinence From End of Treatment (Week 12) to End of Follow up (Week 26)
timeFrame: 26 weeks
measure: Prolonged Abstinence With 2-week Grace Period at End of Follow up (Week 26)
timeFrame: 26 weeks
measure: Continuous Abstinence at 6 Months
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Bernard Le Foll, MD,PhD,MCFP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.