Does the Insula Control Smoking-Induced Dopamine Release? A TMS/[11C]-PHNO Study in Humans.

Not Applicable

Completed

• Conditions: Healthy
• Interventions: Device: repetitive Transcranial Magnetic Stimulation; Other: repetitive Transcranial Magnetic Stimulation Sham

• Registration Number: NCT02212405
• Lead Sponsor: Centre for Addiction and Mental Health

Brief Summary

Findings from this study may demonstrate how the insula contributes to reward pathways involved in addiction. There are three main hypotheses for this trial. The first is that inhibiting the insula using transcranial magnetic stimulation (TMS) will not cause noticeable changes of dopamine release in the striatum. The second is that stimulating the insula with TMS will increase dopamine release in the striatum, and will be visualized on PET imaging as decreased radiotracer binding. The third hypothesis is that the participants will not experience major side effects from TMS on the insula.

Detailed Description

This project will take advantage of the recently developed Deep rTMS coil to target the insular cortex. Few studies have examined the possibility of using repetitive Transcranial Magnetic Stimulation (rTMS) for nicotine addiction and none so far have explored the use of a coil that specifically targets the insular region. The objective of this study is to test whether low and high-frequency rTMS of the insula modulates striatal dopamine (DA) release in healthy humans. Positron Emission Tomography (PET) with \[11C\]-(+)-PHNO, a radiotracer which is very sensitive to fluctuations in DA transmission in the human brain, will be used to assess the impact of rTMS on dopamine levels. This project will yield the first data in humans linking the insula to the DA system in vivo. These findings could lead to the identification of optimal parameters for Deep rTMS to use secondarily in a proof of principle clinical study in smokers.

Study Timeline

• Study Start: 2014-07
• Study First Submitted: 2014-07-30
• Study First Submitted QC: 2014-08-06
• Study First Posted: 2014-08-08
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-30
• Last Update Posted: 2016-09-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

• Healthy male or female
• Between the ages of 19 and 45

Exclusion Criteria

• Pregnancy.
• Presence of metal objects in the body or implanted electronic devices, that preclude safe MR scanning.
• Claustrophobia.
• Cardiovascular or cerebrovascular diseases.
• Major psychiatric disorders including mood, anxiety or psychotic disorders.
• History of or current neurological illnesses including seizure disorders, migraine, multiple sclerosis, movement disorders, head trauma, CVA or CNS tumor.
• Gross structural brain abnormalities as revealed by T1 weighted images.
• Current use or use during the previous month of medication that may affect the CNS (e.g. neuroleptics, bupropion).
• Learning disability, amnesia or other conditions that impede memory and attention.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
rTMS 10Hz + PET.	repetitive Transcranial Magnetic Stimulation	Deep repetitive Transcranial Magnetic Stimulation will be applied to the insula for 30 minutes. This will consist of 34 trains each comprising of 30 pulses at 10Hz. The inter-train interval is 3 seconds. The intervention is followed by radiotracer and PET.
rTMS Sham + PET	repetitive Transcranial Magnetic Stimulation Sham	An advanced sham coil will be used that mimicks the sound and sensation of real repetitive Transcranial Magnetic Stimulation. The repetitive Transcranial Magnetic Stimulation sham intervention is followed by radiotracer and PET.
rTMS 1Hz + PET	repetitive Transcranial Magnetic Stimulation	Deep repetitive Transcranial Magnetic Stimulation will be applied to the insula for 30 minutes. This will consist of 20 trains each comprising of 50 pulses at 1Hz. The inter-train interval is 15 seconds. The intervention is followed by radiotracer and PET.

Primary Outcome Measures

Name	Time	Method
Changes in [11C]-(+)-PHNO binding	Participants will complete all sessions in a period of approximately 4 weeks.	\[11C\]-(+)-PHNO binding at D2/3 receptors will be measured with PET imaging following rTMS at 1Hz, 10Hz, and sham stimulation. Binding at regions of interest will be compared between trial conditions.

Trial Locations

Locations (1)

Centre for Addiction and Mental Health; 🇨🇦 Toronto, Ontario, Canada