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Deep rTMS Modulating Insula Synaptic Density and Smoking Behavior in Schizophrenia

Primary Purpose

Schizophrenia, Smoking Cessation, Tobacco Use

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Active deep transcranial magnetic stimulation (dTMS)
Sham dTMS
Sponsored by
Stony Brook University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring PET, UCB-J, fMRI, Schizophrenia, Smoking Cessation, Tobacco Use

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept 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.

Sites / Locations

  • Stony Brook University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Active deep transcranial magnetic stimulation (dTMS)

Sham

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Symptoms of Psychosis
The positive and negative syndrome scale (PANSS) will be used to measure symptoms of schizophrenia
Nicotine Craving
Craving will be assessed using two self-report items
Cigarettes per Day
Timeline Follow-back Calendars will be administered pre-dTMS and post-dTMS

Full Information

First Posted
January 27, 2023
Last Updated
January 27, 2023
Sponsor
Stony Brook University
Collaborators
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT05724810
Brief Title
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

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
February 2023 (Anticipated)
Primary Completion Date
August 31, 2027 (Anticipated)
Study Completion Date
August 31, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stony Brook University
Collaborators
National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Smoking Cessation, Tobacco Use
Keywords
PET, UCB-J, fMRI, Schizophrenia, Smoking Cessation, Tobacco Use

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
After enrollment, participants will be randomized between-subjects to active dTMS or sham.
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
38 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active deep transcranial magnetic stimulation (dTMS)
Arm Type
Experimental
Arm Description
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.
Arm Title
Sham
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Active deep transcranial magnetic stimulation (dTMS)
Other Intervention Name(s)
repetitive transcranial magnetic stimulation (rTMS)
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Sham dTMS
Intervention Description
Sham group will go through the same procedure. The only difference is that the sham card does not deliver stimulation.
Primary Outcome Measure Information:
Title
Insula synaptic density
Description
PET with UCB-J will be used to look at synaptic density pre/post intervention
Time Frame
pre/post the treatment course over 3 weeks
Title
Smoking self-administration
Description
Laboratory tobacco self-administration will be examined pre/post the intervention as a measure of smoking vigor
Time Frame
pre/post the treatment course over 3 weeks
Title
Insula-centric functional connectivity
Description
fMRI will be used to look at insula circuit functional connectivity pre/post intervention
Time Frame
pre/post the treatment course over 3 weeks
Secondary Outcome Measure Information:
Title
Symptoms of Psychosis
Description
The positive and negative syndrome scale (PANSS) will be used to measure symptoms of schizophrenia
Time Frame
up to 4 times over 3 weeks
Title
Nicotine Craving
Description
Craving will be assessed using two self-report items
Time Frame
post dTMS over 3 weeks
Title
Cigarettes per Day
Description
Timeline Follow-back Calendars will be administered pre-dTMS and post-dTMS
Time Frame
pre/post the treatment course over 3 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anissa Abi-Dargham, MD
Phone
631-638-1575
Email
anissa.abi-dargham@stonybrookmedicine.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Scott J Moeller, PhD
Phone
631-638-3223
Email
scott.moeller@stonybrookmedicine.edu
Facility Information:
Facility Name
Stony Brook University
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anissa Abi-Dargham, MD
Phone
631-638-1575
Email
anissa.abi-dargham@stonybrookmedicine.edu
First Name & Middle Initial & Last Name & Degree
Scott J Moeller, PhD
Phone
631-638-3223
Email
scott.moeller@stonybrookmedicine.edu

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35217662
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.
Results Reference
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Deep rTMS Modulating Insula Synaptic Density and Smoking Behavior in Schizophrenia

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