Repetitive Transcranial Magnetic Stimulation (rTMS) for Nicotine Addiction (rTMS)

Developing rTMS as a Potential Treatment for Nicotine Addiction

Cigarette smoking remains a significant public health concern. A magnetic field applied to the outside of the skull can produce electrical activity in the brain without significant pain or the need for anesthesia. Sessions of magnetic stimulation or superficial stimulation that does not reach the brain will be used to determine if magnetic stimulation can reduce cue-induced craving and cigarettes consumption in adult nicotine-dependent cigarette smokers. This project may lead to a new therapy for smoking cessation.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence
• Intervention / Treatment: Device: Transcranial magnetic stimulation

Detailed Description

Cigarette smoking causes significant morbidity and mortality in the United States. Smoking cessation is difficult, with the average smoker attempting to quit five times before permanent success. Moreover, the majority of smoking quit attempts result in relapse. Brain stimulation for smoke cessation is an exciting new area that builds on advancing neuroscience knowledge concerning the functional neurocircuitry of addiction. Cortical stimulation can now be performed non-invasively by transcranial magnetic stimulation (TMS). A few studies have shown that TMS can reduce cue-elicited craving in smokers. Previous research by our group has shown that a single session of 15 minutes high frequency (10 Hz) repetitive TMS (rTMS) at 100% motor threshold over the left dorsal lateral prefrontal cortex (an area that is likely involved in inhibiting craving) can reduce cue-induced craving compared to sham TMS. However, methodological concerns surrounding these preliminary findings limit definitive conclusions about the effectiveness of TMS over a longer period of time. This R21 proposal will integrate more rigorous experimental conditions, a true double-blind methodology, MRI guided stimulation site and a longer-term follow-up assessment. Using rigorous double-masked methods and MRI guided stimulation site, we propose that using active rTMS or sham rTMS, to determine whether 10 sessions over a two week period consisting of 15 minute high frequency rTMS can reduce cue-induced craving and cigarette consumption for cigarette smokers. The project will also optimize rational rTMS parameters to make TMS to an efficacious treatment for nicotine dependence. In the two years of project, we plan to recruit 42 treatment-seeking nicotine-dependent cigarette smokers, both males and females of all ethnic and racial groups between the ages of 18 and 60 to participate in the study. The 42 participants will be randomly assigned to receive active prefrontal TMS or sham prefrontal TMS. The data from this R21 will provide the information needed for launching a definitive larger-scale investigation into potential clinical applications of TMS in smoke cessation. The results from this pilot will also likely supply substantial information about the utility of cortical stimulation for smoke cessation.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Be between the ages of 18 and 60 years old.
2. Smoke 10 or more cigarettes per day and have a carbon monoxide (CO) level > 10 ppm indicative of recent smoking.
3. Not received substance abuse treatment within the previous 30 days.
4. Meet criteria for nicotine dependence as determined by the FTND.
5. Be in stable mental and physical health.
6. If female, test non-pregnant and use adequate birth control.
7. No evidence of focal or diffuse brain lesion on MRI.
8. Be willing to provide informed consent.
9. Be able to comply with protocol requirements and likely to complete all study procedures.

Exclusion Criteria:

1. Current dependence, defined by DSM-V criteria, on any psychoactive substances other than nicotine or caffeine.
2. Contraindication to MRI (e.g., presence of metal in the skull, orbits or intracranial cavity, claustrophobia).
3. Contraindication to rTMS (history of neurological disorder or seizure, increased intracranial pressure, brain surgery, or head trauma with loss of consciousness for > 15 minutes, implanted electronic device, metal in the head, or pregnancy).
4. History of autoimmune, endocrine, viral, or vascular disorder affecting the brain.
5. History or MRI evidence of neurological disorder that would lead to local or diffuse brain lesions or significant physical impairment.
6. Unstable cardiac disease, uncontrolled hypertension, severe renal or liver insufficiency, or sleep apnea.
7. Life time history of major Axis I disorders such as: Bipolar Affective disorder (BPAD), Schizophrenia, Post-traumatic Stress disorder (PTSD) or Dementia or Major Depression.
8. Self report of >21 standard alcohol drinks per week in any week in the 30 days prior to screening.
9. Other forms of nicotine delivery, such as nicotine patch, electronic cigarettes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active TMS; Repetitive TMS pulse stimulation	Device: Transcranial magnetic stimulation; Transcranial magnetic stimulation (TMS) is a noninvasive (and relatively painless) brain stimulation technology that can focally stimulate the brain of an awake individual. A localized pulsed magnetic field transmitted through a TMS coil is able to focally stimulate the cortex by depolarizing superficial neurons inducing electrical currents in the brain. If TMS pulses are delivered repetitively and rhythmically, the process is called repetitive TMS (rTMS).
Sham Comparator: Sham TMS; The sham TMS system will be connected to an electrical generator on a 9 V battery and electrodes will be placed over the prefrontal cortex. The regulator is triggered by the TMS machine to allow brief, microsecond, pulses of the electrical current through to the skin on the subjects' forehead. Electrical stimulation will be triggered by the TMS machine to correspond to the sham TMS pulses.	Device: Transcranial magnetic stimulation; Transcranial magnetic stimulation (TMS) is a noninvasive (and relatively painless) brain stimulation technology that can focally stimulate the brain of an awake individual. A localized pulsed magnetic field transmitted through a TMS coil is able to focally stimulate the cortex by depolarizing superficial neurons inducing electrical currents in the brain. If TMS pulses are delivered repetitively and rhythmically, the process is called repetitive TMS (rTMS).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine Consumption: Number of Cigarettes Per Day	Nicotine consumption: We use cigarette diary for participant to record number of cigarettes smoked per day.	2 weeks of treatment
Percentage of Change of Cigarettes Per Day	percentage of change of cigarettes per day =100* ( cigarettes smoked per day at baseline - cigarettes smoked per day at the end of treatment) / cigarettes smoked per day at baseline	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Nicotine Craving as Assessed by the Questionnaire of Smoking Urges-Brief	The Brief Questionnaire of Smoking Urges (QSU-Brief) consists of 10 statements about the respondent's feelings and thoughts about his or her desire to smoke cigarettes as he or she is completing the questionnaire. A higher number represents a stronger smoking urges. A lower score represents a weaker smoking urges. The lowest score is 10. The highest score is 70.	2 weeks of treatment
The Number of Participants Quitting on the Target Quit Date	Quitting smoking on the target quit date.	2 weeks of treatment

Collaborators and Investigators

• Sponsor: Medical University of South Carolina

Publications and helpful links

General Publications

• Li X, Hartwell KJ, Owens M, Lematty T, Borckardt JJ, Hanlon CA, Brady KT, George MS. Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue craving. Biol Psychiatry. 2013 Apr 15;73(8):714-20. doi: 10.1016/j.biopsych.2013.01.003. Epub 2013 Feb 26.
• Li X, Hartwell KJ, Henderson S, Badran BW, Brady KT, George MS. Two weeks of image-guided left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation improves smoking cessation: A double-blind, sham-controlled, randomized clinical trial. Brain Stimul. 2020 Sep-Oct;13(5):1271-1279. doi: 10.1016/j.brs.2020.06.007. Epub 2020 Jun 10.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2014
• Primary Completion (Actual): December 30, 2018
• Study Completion (Actual): December 30, 2018

Study Registration Dates

• First Submitted: March 16, 2015
• First Submitted That Met QC Criteria: March 24, 2015
• First Posted (Estimate): March 30, 2015

Study Record Updates

• Last Update Posted (Actual): September 21, 2020
• Last Update Submitted That Met QC Criteria: August 31, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: nicotine dependence; smoking cessation; TMS
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder
• Other Study ID Numbers: pro00032313

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: Yes