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

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ClinicalTrials.gov Identifier: NCT02212405
Recruitment Status : Completed
First Posted : August 8, 2014
Last Update Posted : September 1, 2016
Sponsor:
Collaborator:
Brainsway
Information provided by (Responsible Party):
Bernard Le Foll, 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.

Condition or disease Intervention/treatment Phase
Healthy Device: repetitive Transcranial Magnetic Stimulation Other: repetitive Transcranial Magnetic Stimulation Sham Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Does the Insula Control Smoking-Induced Dopamine Release? A TMS/[11C]-PHNO Study in Humans (Part II).
Study Start Date : July 2014
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Sham Comparator: rTMS Sham + PET
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.
Other: repetitive Transcranial Magnetic Stimulation Sham
The sham coil is built in the same helmet of the active coil. The sham coil is has a circular shape and placed perpendicular to the scalp within the same helmet. This coil produces a similar sound and scalp sensation as the real coil.

Experimental: rTMS 1Hz + PET
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.
Device: repetitive Transcranial Magnetic Stimulation
Each participant will participate in all three arms to receive sham, 1hz and 10hz rTMS as well as PET imaging.
Other Names:
  • Deep Repetitive Transcranial Magnetic Stimulation
  • DTMS HLRIADD-COIL, Model 102B

Experimental: rTMS 10Hz + PET.
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.
Device: repetitive Transcranial Magnetic Stimulation
Each participant will participate in all three arms to receive sham, 1hz and 10hz rTMS as well as PET imaging.
Other Names:
  • Deep Repetitive Transcranial Magnetic Stimulation
  • DTMS HLRIADD-COIL, Model 102B




Primary Outcome Measures :
  1. Changes in [11C]-(+)-PHNO binding [ Time Frame: 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.



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Ages Eligible for Study:   19 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02212405


Locations
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Canada, Ontario
Centre for Addiction and Mental Health
Toronto, Ontario, Canada, M5S 2S1
Sponsors and Collaborators
Centre for Addiction and Mental Health
Brainsway
Investigators
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Principal Investigator: Bernard LeFoll, M.D., Ph.D CAMH

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bernard Le Foll, Principal investigator, MD, PhD, CCFP, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT02212405     History of Changes
Other Study ID Numbers: 170/2010
First Posted: August 8, 2014    Key Record Dates
Last Update Posted: September 1, 2016
Last Verified: August 2016
Keywords provided by Bernard Le Foll, Centre for Addiction and Mental Health:
Deep rTMS
Insular cortex
PET
[11C]-PHNO
Additional relevant MeSH terms:
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Dopamine
Cardiotonic Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents