Network-Targeted Neuromodulation for Nicotine Dependence in Schizophrenia

NCT06389266 | Completed DMC FDA Device

• 1 other identifier: 221550
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to compare two active types of transcranial magnetic stimulation in two nicotine-using populations: nicotine-using people with psychosis and nicotine-using people without a diagnosis of a psychotic disorder. The main questions it aims to answer are:

1. 1.Can rTMS change functional connectivity in brain circuits associated with nicotine use?
2. 2.Are those rTMS-induced changes in functional connectivity related to craving?

Conditions

Schizophrenia; Nicotine Dependence

Outcome Measures

Primary Outcomes (4)

• Resting-state functional connectivity

  The investigators will evaluate the effect of DMN-targeted cTBS on functional connectivity of the left parietal node of the DMN and the entire default mode network. The investigators will also evaluate the effect of L DLPFC-targeted iTBS on functional connectivity of the L DLPFC.

  Baseline to one week, and three weeks to five weeks

• Cue-induced craving

  The investigators will evaluate the effect of DMN-targeted cTBS and L DLPFC-targeted iTBS on self-reported craving before and after presentation of visual nicotine cues. Craving is measured on a scale from 0 to 10, with 10 being the highest level of craving.

  Baseline to one week, and three weeks to five weeks

• Tiffany Brief Questionnaire of Smoking Urges (QSU)

  The investigators will evaluate the effect of DMN-targeted cTBS and L DLPFC-targeted iTBS on QSU scores. The QSU-Brief has a range of 10-70, with higher scores indicating higher smoking urges.

  Baseline to one week, and three weeks to five weeks

• Self-reported craving

  The investigators will evaluate the effect of DMN-targeted cTBS and L DLPFC-targeted iTBS on self-reported craving, measured by a Visual Analog Scale of nicotine craving. Craving is measured on a scale from 0 to 10, with 10 being the highest level of craving.

  Baseline to one week, and three weeks to five weeks

Secondary Outcomes (3)

• Wisconsin Smoking Withdrawal Scale (WSWS)

  Baseline to one week, and three weeks to five weeks

• Fagerstrom Test for Nicotine Dependence (FTND)

  Baseline to one week, and three weeks to five weeks

• Self-reported nicotine use

  Baseline to one week, and three weeks to five weeks

Study Arms (2)

L DLPFC-Targeted iTBS, Then DMN-Targeted cTBS

ACTIVE COMPARATOR

Participants will first receive intermittent theta burst stimulation (iTBS) at 100% active motor threshold (AMT) anatomically targeted to the left dorsolateral prefrontal cortex for five consecutive days. iTBS will be administered in a pattern consisting of 2s trains of 3 pulses at 50Hz, repeated at 5Hz, every 10s for a total of 600 pulses. There will then be a washout period of at least two weeks before starting the DMN-Targeted cTBS. Participants will then receive continuous theta burst stimulation (cTBS) at 100% AMT targeted to an individual-specific map of the left parietal node of the default mode network for five consecutive days. cTBS will be administered in a pattern consisting of 1 60s train of 3 pulses at 50Hz, repeated at 5Hz, for a total of 600 pulses.

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

DMN-Targeted cTBS, Then L DLPFC-Targeted iTBS

ACTIVE COMPARATOR

Participants will first receive continuous theta burst stimulation (cTBS) at 100% AMT targeted to an individual-specific map of the left parietal node of the default mode network for five consecutive days. cTBS will be administered in a pattern consisting of 1 60s train of 3 pulses at 50Hz, repeated at 5Hz, for a total of 600 pulses. There will then be a washout period of at least two weeks before starting the L DLPFC-Targeted iTBS. Participants will receive intermittent theta burst stimulation (iTBS) at 100% active motor threshold (AMT) anatomically targeted to the left dorsolateral prefrontal cortex for five consecutive days. iTBS will be administered in a pattern consisting of 2s trains of 3 pulses at 50Hz, repeated at 5Hz, every 10s for a total of 600 pulses.

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Interventions

Repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

rTMS is a technique of TMS that allows the selective external manipulation of neural activity in a non-invasive manner. During TMS, a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field that in turn induces electrical current in neurons and allows the modulation of neural circuitry. The combination of rTMS with functional magnetic resonance imaging allows the selective targeting and modulation of brain networks. The repeated application of rTMS can cause long term changes in behavior and task performance that is reflected in altered brain network connectivity.

DMN-Targeted cTBS, Then L DLPFC-Targeted iTBS; L DLPFC-Targeted iTBS, Then DMN-Targeted cTBS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18-65 years
• Diagnosis of either schizophrenia or schizoaffective disorder according to Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria and confirmed by Structured Clinical Interview for the DSM (SCID) (First et al. 2015)
• Current nicotine use (confirmed by expired carbon monoxide or urine cotinine)
• Must be able to read, speak and understand English
• Must be judged by study staff to be capable of completing the study procedures
• Participants will be in stable outpatient psychiatric treatment and psychiatrically stable with no recent (within the past 90 days) psychiatric hospitalizations or changes in their psychiatric medication regimens.
• \- All of the above except for participants will not have a diagnosis of schizophrenia or schizoaffective disorder nor a first-degree relative with a psychotic disorder.

You may not qualify if:

• DSM-5 intellectual disability
• Substance use disorder (other than nicotine) within the past three months Positive urine drug screen for illicit substance use that can increase seizure risk (cocaine, benzodiazepines, amphetamine, methamphetamine)
• Any history of a progressive or genetic neurologic disorder (e.g. Parkinson's disease, multiple sclerosis, tuberous sclerosis, Alzheimer's Disease) or acquired neurological disease (e.g. stroke, traumatic brain injury, tumor), including intracranial lesions
• History of head trauma resulting in any loss of consciousness (\>15 minutes) or neurological sequelae
• Current history of poorly controlled headaches including chronic medication for migraine prevention
• History of fainting spells of unknown or undetermined etiology that might constitute seizures
• History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy with the exception of a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist
• Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)
• Any metal in the brain or skull (excluding dental fillings) or elsewhere in the body unless cleared by the responsible covering MD (e.g. MRI compatible joint replacement)
• Any devices such as pacemaker, medication pump, nerve stimulator, transcutaneous electrical nerve stimulation (TENS) unit, ventriculo-peritoneal shunt unless cleared by the responsible covering MD
• All female participants of child-bearing age will be required to have a pregnancy test; any participant who is pregnant or planning to become pregnant will not be enrolled in the study
• Any changes in medications or hospitalizations within the past 90 days.
• Participants who, in the investigator's opinion, might not be suitable for the study or would be unable to tolerate the study visit

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (3)

• Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.

  PMID: 15664172 BACKGROUND

• Tseng PT, Zeng BS, Hung CM, Liang CS, Stubbs B, Carvalho AF, Brunoni AR, Su KP, Tu YK, Wu YC, Chen TY, Li DJ, Lin PY, Hsu CW, Chen YW, Suen MW, Satogami K, Takahashi S, Wu CK, Yang WC, Shiue YL, Huang TL, Li CT. Assessment of Noninvasive Brain Stimulation Interventions for Negative Symptoms of Schizophrenia: A Systematic Review and Network Meta-analysis. JAMA Psychiatry. 2022 Aug 1;79(8):770-779. doi: 10.1001/jamapsychiatry.2022.1513.

  PMID: 35731533 BACKGROUND

• Bassett DS, Sporns O. Network neuroscience. Nat Neurosci. 2017 Feb 23;20(3):353-364. doi: 10.1038/nn.4502.

  PMID: 28230844 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Tobacco Use Disorder

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Heather B Ward, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The study is not sham-controlled, as both arms are active TMS treatments. The type of TMS is not masked from the participant or the investigator. Statistician will be blinded to intervention.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: All participants receive five days of DMN-targeted cTBS and five days of L DLPFC-targeted iTBS. The order in which participants receive the two types of TMS is randomized.

Study Record Dates

• First Submitted: April 24, 2024
• First Posted: April 29, 2024
• Study Start: June 15, 2023
• Primary Completion: September 15, 2025
• Study Completion: September 22, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

US (1)