Schizophrenia, Smoking Cessation, Tobacco Use
Conditions
Keywords
PET, UCB-J, fMRI, Schizophrenia, Smoking Cessation, Tobacco Use
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.
Interventions
DEVICEActive deep transcranial magnetic stimulation (dTMS)
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.
DEVICESham dTMS
Sham group will go through the same procedure. The only difference is that the sham card does not deliver stimulation.
Sponsors
Stony Brook University
National Institute on Drug Abuse (NIDA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
Intervention model description
After enrollment, participants will be randomized between-subjects to active dTMS or sham.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insula synaptic density | Change from Baseline at 3 weeks | PET with UCB-J will be used to look at synaptic density 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-centric functional connectivity | Change from Baseline at 3 weeks | fMRI will be used to look at insula circuit functional connectivity pre/post intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Change from Baseline at 3 weeks | Timeline Follow-back Calendars will be administered pre-dTMS and post-dTMS |
Countries
United States
Outcome results
None listed