Clinical trial NCT02401672: Repetitive Transcranial Magnetic Stimulation (rTMS) for Nicotine Addiction
Official title: Developing rTMS as a Potential Treatment for Nicotine Addiction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nicotine Dependence
Keywords: TMS
nicotine dependence
smoking cessation
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2015-03-30
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Nicotine Consumption: Number of Cigarettes Per Day
timeFrame: 2 weeks of treatment
measure: Percentage of Change of Cigarettes Per Day
timeFrame: 2 weeks
Secondary outcomes:
measure: Average Nicotine Craving as Assessed by the Questionnaire of Smoking Urges-Brief
timeFrame: 2 weeks of treatment
measure: The Number of Participants Quitting on the Target Quit Date
timeFrame: 2 weeks of treatment
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
References:
citation: 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.
citation: 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.