Clinical trial NCT05724810: Deep rTMS Modulating Insula Synaptic Density and Smoking Behavior in Schizophrenia
Official title: Deep rTMS Modulating Insula Synaptic Density and Smoking Behavior in Schizophrenia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Schizophrenia
Smoking Cessation
Tobacco Use
Keywords: PET
UCB-J
fMRI
Schizophrenia
Smoking Cessation
Tobacco Use
Lead sponsor: Stony Brook University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2023-02-13
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After enrollment, participants will be randomized between-subjects to active dTMS or sham.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Insula synaptic density
timeFrame: Change from Baseline at 3 weeks
measure: Smoking self-administration
timeFrame: Change from Baseline at 3 weeks
measure: Insula-centric functional connectivity
timeFrame: Change from Baseline at 3 weeks
Secondary outcomes:
measure: Symptoms of Psychosis
timeFrame: up to 4 times over 3 weeks
measure: Nicotine Craving
timeFrame: post dTMS over 3 weeks
measure: Cigarettes per Day
timeFrame: Change from Baseline at 3 weeks
Other outcomes:
Locations:
city: Stony Brook
country: United States
facility: Stony Brook University
state: New York
Study officials:
References:
citation: 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.