Deep rTMS Modulating Insula Synaptic Density and Smoking Behavior in Schizophrenia

Not Applicable

Recruiting

• Conditions: Smoking Cessation; Schizophrenia; Tobacco Use
• Interventions: Device: Sham dTMS; Device: Active deep transcranial magnetic stimulation (dTMS)

• Registration Number: NCT05724810
• Lead Sponsor: Stony Brook University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-01-27
• Study First Submitted QC: 2023-01-27
• Study First Posted: 2023-02-13
• Study Start: 2023-04-04
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-23
• Last Update Posted: 2024-04-25
• Primary Completion: 2027-08-31
• Study Completion: 2028-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 38

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham	Sham dTMS	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.
Active deep transcranial magnetic stimulation (dTMS)	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Stony Brook University; 🇺🇸 Stony Brook, New York, United States