Deep rTMS Modulating Insula Synaptic Density and Smoking Behavior in Schizophrenia

Schizophrenia Clinical Trial

Official title:

Deep rTMS Modulating Insula Synaptic Density and Smoking Behavior in Schizophrenia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05724810
• Other study ID #: 1R61DA056423
• Status: Recruiting
• Phase: N/A
• Start date: April 4, 2023
• Est. completion date: August 31, 2028

Study information

• Verified date: April 2024
• Source: Stony Brook University
• Contact: Anissa Abi-Dargham, MD
• Phone: 631-638-1575
• Email: anissa.abi-dargham[@]stonybrookmedicine.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 38
• Est. completion date: August 31, 2028
• Est. primary completion date: August 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Schizophrenia
• Smoking Cessation
• Tobacco Use

Intervention

Device:
• Active 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.
• Sham dTMS
Sham group will go through the same procedure. The only difference is that the sham card does not deliver stimulation.

Locations

Country	Name	City	State
United States	Stony Brook University	Stony Brook	New York

Sponsors (2)

Lead Sponsor	Collaborator
Stony Brook University	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insula synaptic density	PET with UCB-J will be used to look at synaptic density pre/post intervention	Change from Baseline at 3 weeks
Primary	Smoking self-administration	Laboratory tobacco self-administration will be examined pre/post the intervention as a measure of smoking vigor	Change from Baseline at 3 weeks
Primary	Insula-centric functional connectivity	fMRI will be used to look at insula circuit functional connectivity pre/post intervention	Change from Baseline at 3 weeks
Secondary	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
Secondary	Nicotine Craving	Craving will be assessed using two self-report items	post dTMS over 3 weeks
Secondary	Cigarettes per Day	Timeline Follow-back Calendars will be administered pre-dTMS and post-dTMS	Change from Baseline at 3 weeks