Deep rTMS Modulating Insula Synaptic Density and Smoking Behavior in Schizophrenia

Sponsor

Stony Brook University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05724810

Collaborator

National Institute on Drug Abuse (NIDA) (NIH)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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. 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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Smoking Cessation Tobacco Use	Device: Active deep transcranial magnetic stimulation (dTMS) Device: Sham dTMS	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

38 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

After enrollment, participants will be randomized between-subjects to active dTMS or sham.After enrollment, participants will be randomized between-subjects to active dTMS or sham.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Active and sham cards do not differ in appearance, and both coils are enclosed within the same helmet, enabling double-blind administration.

Primary Purpose:

Treatment

Official Title:

Deep rTMS Modulating Insula Synaptic Density and Smoking Behavior in Schizophrenia

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Aug 31, 2027

Anticipated Study Completion Date :

Aug 31, 2028

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Insula synaptic density [pre/post the treatment course over 3 weeks]
PET with UCB-J will be used to look at synaptic density pre/post intervention
Smoking self-administration [pre/post the treatment course over 3 weeks]
Laboratory tobacco self-administration will be examined pre/post the intervention as a measure of smoking vigor
Insula-centric functional connectivity [pre/post the treatment course over 3 weeks]
fMRI will be used to look at insula circuit functional connectivity pre/post intervention

Secondary Outcome Measures

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
Nicotine Craving [post dTMS over 3 weeks]
Craving will be assessed using two self-report items
Cigarettes per Day [pre/post the treatment course over 3 weeks]
Timeline Follow-back Calendars will be administered pre-dTMS and post-dTMS

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Clinically significant psychopathology other than schizophrenia, schizophreniform, schizoaffective disorder, or psychotic disorder NOS
Current or past substance use disorder, except TUD
Current use of smoking cessation medications/products
Change in schizophrenia medication within 4 weeks
Hospitalization in the last 3 months
History of suicidal or homicidal tendencies
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)

Pregnancy or lactation (females)
Lack of effective birth control (females)
Contraindications to MRI or PET
Clinical Global Impressions (CGI) rating of 6 (severely ill) or 7 (extremely ill)
Prisoners
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.