Deep rTMS Modulating Insula Synaptic Density and Smoking Behavior in Schizophrenia

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. We 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

• Status: Not yet recruiting
• Conditions: Smoking Cessation; Schizophrenia; Tobacco Use
• Intervention / Treatment: Device: Active deep transcranial magnetic stimulation (dTMS); Device: Sham dTMS

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anissa Abi-Dargham, MD; Phone Number: 631-638-1575; Email: anissa.abi-dargham@stonybrookmedicine.edu
• Study Contact Backup: Name: Scott J Moeller, PhD; Phone Number: 631-638-3223; Email: scott.moeller@stonybrookmedicine.edu

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook University
      • Contact: Anissa Abi-Dargham, MD; Phone Number: 631-638-1575; Email: anissa.abi-dargham@stonybrookmedicine.edu
      • Contact: Scott J Moeller, PhD; Phone Number: 631-638-3223; Email: scott.moeller@stonybrookmedicine.edu

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. 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." We will monitor the FDA guidelines and implement any changes to the inclusion/exclusion criteria based on their most updated recommendations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

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.	Device: Active deep transcranial magnetic stimulation (dTMS); First, we 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.	Device: Sham dTMS; 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	PET with UCB-J will be used to look at synaptic density pre/post intervention	pre/post the treatment course over 3 weeks
Smoking self-administration	Laboratory tobacco self-administration will be examined pre/post the intervention as a measure of smoking vigor	pre/post the treatment course over 3 weeks
Insula-centric functional connectivity	fMRI will be used to look at insula circuit functional connectivity pre/post intervention	pre/post the treatment course over 3 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Stony Brook University
• Collaborators: National Institute on Drug Abuse (NIDA)

Publications and helpful links

General Publications

• Moeller SJ, Gil R, Weinstein JJ, Baumvoll T, Wengler K, Fallon N, Van Snellenberg JX, Abeykoon S, Perlman G, Williams J, Manu L, Slifstein M, Cassidy CM, Martinez DM, Abi-Dargham A. Deep rTMS of the insula and prefrontal cortex in smokers with schizophrenia: Proof-of-concept study. Schizophrenia (Heidelb). 2022 Feb 25;8(1):6. doi: 10.1038/s41537-022-00224-0.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 1, 2023
• Primary Completion (ANTICIPATED): August 31, 2027
• Study Completion (ANTICIPATED): 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): February 13, 2023
• Last Update Submitted That Met QC Criteria: January 27, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Schizophrenia; PET; fMRI; Tobacco Use; Smoking Cessation; UCB-J
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 1R61DA056423 (NIH)

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