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RTMS Targets Neural Circuits for Smoking Cessation

RTMS Targets Neural Circuits for Smoking Cessation

Recruiting
18-60 years
All
Phase 1/2

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Overview

Cigarette smoking is a significant public health concern. Transcranial magnetic stimulation (TMS) is a non-invasive form of brain stimulation that has already displayed remarkable potential for producing novel, non-pharmacological interventions for depression and cigarette smokers. In this study, we will use brain MRI to guide TMS therapy for smoking cessation.

Description

Smoking cessation is difficult, despite the demonstrated efficacy of several pharmacotherapeutic agents and cognitive behavioral therapies. This may be due to imbalanced neuronal circuits, including elevated functional connectivity in the drive-reward circuit (medial orbital frontal cortex [mOFC] to nucleus accumbens [NAc]) and decreased functional connectivity in the executive control circuit (dorsolateral prefrontal cortex[ DLPFC] to NAc). Repetitive transcranial magnetic stimulation (rTMS) is a new class of therapeutics that has already displayed remarkable potential for producing novel, non-pharmacological interventions for neuropsychiatric disorders. Previous studies have reported that rTMS decreased cue craving, reduced cigarette consumption, and increased smoking quit rate in tobacco use disorders(TUDs). However, the treatment parameters and exact mechanism for rTMS increasing smoking quit rate need further refinement. The goal of this study is to develop a circuit-based precision rTMS therapy for smoking cessation further. In the 2-year UG3 phase, investigators will recruit 45 TUDs. Participants will undergo a baseline cue-exposure fMRI and a resisting-to smoke fMRI session. Participants will be randomized into three groups: 1) Sham rTMS over the left mOFC or the left DLPFC. 2) Active, inhibitory low-frequency rTMS (LF-rTMS) over the left mOFC (1 Hz, 900 pulses, E-field modeling, 15 minutes, smoking cue exposure fMRI-guided target). Or 3) Active, high-frequency rTMS (HF-rTMS) over the left DLPFC (10 Hz, 3000 pulses, E-field modeling,15 minutes, resisting-to-smoke fMRI guided target). Fifteen sessions of rTMS will be completed over three weeks, after which the investigators will acquire fMRI scans. The investigators will also test the imbalanced function of drive-reward and executive control before and after 3 weeks of treatments to compare the imbalanced function between groups.

Eligibility

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. Have not received substance abuse treatment within the previous 30 days.
  4. Meet the criteria for tobacco use disorder as determined by DSM-5.
  5. Be in stable mental and physical health.
  6. If female, test non-pregnant and use adequate birth control.
  7. Show no evidence of focal or diffuse brain lesions on MRI.
  8. Be willing to provide informed consent.
  9. Be able to comply with protocol requirements and likely to complete all study procedures.
  10. Be motivated to quit smoking (based on responses of "very likely," or "somewhat likely" in the motivation questionnaire).

Exclusion Criteria:

  1. Current moderate to severe substance use of any psychoactive substances other than nicotine or caffeine, as defined by DSM-V criteria.
  2. Contraindications to MRI (e.g., presence of metal in the skull, orbital or intracranial cavity, or having claustrophobia).
  3. Contraindication to rTMS.
  4. History of autoimmune, endocrine, viral, or vascular disorders 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. Lifetime history of major Axis I disorders such as: bipolar affective disorder (BPAD), schizophrenia, post-traumatic stress disorder (PTSD), dementia, suicidal ideation or major depression.
  8. Self-report of >21 standard alcohol drinks per week in any week in the 30 days prior to screening.
  9. Use of other forms of nicotine delivery, such as nicotine patches, electronic cigarettes, gum, nasal spray, inhalers, and nicotine lozenges.
  10. Use of other tobacco products, including cigars, cigarillos, chew, snuff, and pouches/snus.
  11. Previous treatment with TMS.

Study details
    Tobacco Use
    Cigarette Smoking

NCT04903028

Medical University of South Carolina

27 January 2024

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