Deep rTMS Modulating Insula Synaptic Density and Smoking Behavior in Schizophrenia

April 23, 2024 updated by: Anissa Abi-Dargham, Stony Brook University

Purpose of the study: Evaluate the effect of deep repetitive transcranial magnetic stimulation (deep rTMS; hereafter abbreviated as "dTMS") on synaptic density measured with positron emission tomography (PET) and the radiotracer [11C]UCB-J. The investigators also seek to link plasticity changes in the regions targeted by the electric field (especially, the insula) to changes in the functioning of insula circuits and behavioral cigarette usage in patients with schizophrenia (SCZ).

Importance of the study: This is the first study designed to directly evaluate the mechanism of action (MOA) of dTMS for smoking disruption in patients with SCZ. Patients with SCZ are a vulnerable population in high, immediate need of new smoking therapeutics for reducing premature morbidity and mortality.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

38

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Ages 18-60
  2. DSM-5 criteria for schizophreniform, schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified (NOS).
  3. DSM-5 diagnosis of nicotine use disorder with current daily smoking, and a desire to cut down or quit.
  4. Negative urine toxicology (other than cannabis) maintained throughout study participation
  5. Fluent English Speaker
  6. Capacity for informed consent

Exclusion Criteria:

  1. Clinically significant psychopathology other than schizophrenia, schizophreniform, schizoaffective disorder, or psychotic disorder NOS
  2. Current or past substance use disorder, except TUD
  3. Current use of smoking cessation medications/products
  4. Change in schizophrenia medication within 4 weeks
  5. Hospitalization in the last 3 months
  6. History of suicidal or homicidal tendencies
  7. History of epilepsy, stroke, cerebral aneurysm, significant head injury resulting in >10 min loss of consciousness, movement disorder, clinically significant electrolyte abnormalities, or use of clozapine (seizure risks)
  8. Pregnancy or lactation (females)
  9. Lack of effective birth control (females)
  10. Contraindications to MRI or PET
  11. Clinical Global Impressions (CGI) rating of 6 (severely ill) or 7 (extremely ill)
  12. Prisoners
  13. Contraindications to dTMS*

    • The FDA website currently states that the Brainsway device used in this study is contraindicated for patients who have "metallic objects or implanted stimulator devices in or near the head, including cochlear implants, deep brain stimulators, vagus nerve stimulators, other implanted electrodes or stimulators, aneurysm clips or coils, stents, bullet fragments, jewelry and hair barrettes." The investigators will monitor the FDA guidelines and implement any changes to the inclusion/exclusion criteria based on their most updated recommendations.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active deep transcranial magnetic stimulation (dTMS)
Each treatment consists of 60 trains, each lasting 3 sec and interleaved with a 15 sec delay. The entire treatment is delivered over 20 min. The treatment goes for 5 days/week and for a total of 3 weeks.
First, the investigators will find the position of the right abductor pollicis brevis (APB) motor cortex, finding the minimal motor threshold (MT) required for its activation, which determines the strength of the pulses. After determining the MT, dTMS stimulation is applied 6 cm anterior to the motor "hot spot", at 120% of the MT. The target threshold is built toward gradually. During the first treatment, participants receive stimulation at 100% of the MT. During the second treatment, stimulation intensity increases to 110% of the MT. Beginning at the third treatment and continuing onward, participants receive treatment at 120% of the MT for the course of the treatment.
Other Names:
  • repetitive transcranial magnetic stimulation (rTMS)
Sham Comparator: Sham
Active and sham cards do not differ in appearance, and both coils are enclosed within the same helmet, enabling double-blind administration. The same procedure will be done, the only difference is that the sham card does not deliver any stimulation.
Sham group will go through the same procedure. The only difference is that the sham card does not deliver stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insula synaptic density
Time Frame: Change from Baseline at 3 weeks
PET with UCB-J will be used to look at synaptic density pre/post intervention
Change from Baseline at 3 weeks
Smoking self-administration
Time Frame: Change from Baseline at 3 weeks
Laboratory tobacco self-administration will be examined pre/post the intervention as a measure of smoking vigor
Change from Baseline at 3 weeks
Insula-centric functional connectivity
Time Frame: Change from Baseline at 3 weeks
fMRI will be used to look at insula circuit functional connectivity pre/post intervention
Change from Baseline at 3 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Symptoms of Psychosis
Time Frame: up to 4 times over 3 weeks
The positive and negative syndrome scale (PANSS) will be used to measure symptoms of schizophrenia
up to 4 times over 3 weeks
Nicotine Craving
Time Frame: post dTMS over 3 weeks
Craving will be assessed using two self-report items
post dTMS over 3 weeks
Cigarettes per Day
Time Frame: Change from Baseline at 3 weeks
Timeline Follow-back Calendars will be administered pre-dTMS and post-dTMS
Change from Baseline at 3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 4, 2023

Primary Completion (Estimated)

August 31, 2027

Study Completion (Estimated)

August 31, 2028

Study Registration Dates

First Submitted

January 27, 2023

First Submitted That Met QC Criteria

January 27, 2023

First Posted (Actual)

February 13, 2023

Study Record Updates

Last Update Posted (Actual)

April 25, 2024

Last Update Submitted That Met QC Criteria

April 23, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • 1R61DA056423 (U.S. NIH Grant/Contract)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Smoking Cessation

Clinical Trials on Sham dTMS

3
Subscribe