HealthyNCT02212405
Does the Insula Control Smoking-Induced Dopamine Release? A TMS/[11C]-PHNO Study in Humans.
A study testing repetitive Transcranial Magnetic Stimulation in people with Healthy, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- repetitive Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2014to Dec 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male or female
- Between the ages of 19 and 45
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Does the Insula Control Smoking-Induced Dopamine Release? A TMS/[11C]-PHNO Study in Humans (Part II).
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.
Read the 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.
- Conditions
- Healthy
- Being tested
- repetitive Transcranial Magnetic Stimulation, repetitive Transcranial Magnetic Stimulation Sham
- Keywords
- Deep rTMS, Insular cortex, PET, [11C]-PHNO
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
repetitive Transcranial Magnetic StimulationDevice
Also called Deep Repetitive Transcranial Magnetic Stimulation, DTMS HLRIADD-COIL, Model 102B
Each participant will participate in all three arms to receive sham, 1hz and 10hz rTMS as well as PET imaging.
repetitive Transcranial Magnetic Stimulation ShamOther
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.
| Study group | Role | What they receive |
|---|---|---|
| rTMS Sham + PET | Sham comparator | 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. Receives: Other: repetitive Transcranial Magnetic Stimulation Sham |
| rTMS 1Hz + PET | Experimental | 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. Receives: Device: repetitive Transcranial Magnetic Stimulation |
| rTMS 10Hz + PET. | Experimental | 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. Receives: Device: repetitive Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in [11C]-(+)-PHNO binding
[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.
Measured: Participants will complete all sessions in a period of approximately 4 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2014 (estimated)
- Study startJul 2014
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Brainsway
- Responsible party
- Principal investigator, Bernard Le Foll, Centre for Addiction and Mental Health
- Investigators
- Bernard LeFoll, M.D., Ph.D, Principal investigator, CAMH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02212405
- Sponsor's protocol ID
- 170/2010
- Status last verified
- Aug 2016
- First submitted
- 30 Jul 2014
- Last updated
- 1 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Malik S, Jacobs M, Cho SS, Boileau I, Blumberger D, Heilig M, Wilson A, Daskalakis ZJ, Strafella AP, Zangen A, Le Foll B. Deep TMS of the insula using the H-coil modulates dopamine release: a crossover [11C] PHNO-PET pilot trial in healthy humans. Brain Imaging Behav. 2018 Oct;12(5):1306-1317. doi: 10.1007/s11682-017-9800-1.
PubMed 29170944
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does the Insula Control Smoking-Induced Dopamine Release? A TMS/[11C]-PHNO Study in Humans (Part II).
- ClinicalTrials.gov ID
- NCT02212405
- Acronym / sponsor ID
- 170/2010
- Conditions
- Healthy
- Keywords
- Deep rTMS, Insular cortex, PET, [11C]-PHNO
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- Brainsway
- Study start
- Jul 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 8 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| rTMS Sham + PET | Sham comparator | Other: repetitive Transcranial Magnetic Stimulation ShamAn 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 | Experimental | Device: repetitive Transcranial Magnetic StimulationDeep 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. |
| rTMS 10Hz + PET. | Experimental | Device: repetitive Transcranial Magnetic StimulationDeep 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. |
Who may qualify
- Ages
- 19 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy male or female
- Between the ages of 19 and 45
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| repetitive Transcranial Magnetic StimulationAlso: Deep Repetitive Transcranial Magnetic Stimulation, DTMS HLRIADD-COIL, Model 102BEach participant will participate in all three arms to receive sham, 1hz and 10hz rTMS as well as PET imaging. | Device | rTMS 10Hz + PET., rTMS 1Hz + PET |
| repetitive Transcranial Magnetic Stimulation ShamThe 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. | Other | rTMS Sham + PET |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2016.
- Derived from this study: PubMed 29170944Malik S, Jacobs M, Cho SS, Boileau I, Blumberger D, Heilig M, Wilson A, Daskalakis ZJ, Strafella AP, Zangen A, Le Foll B. Deep TMS of the insula using the H-coil modulates dopamine release: a crossover [11C] PHNO-PET pilot trial in healthy humans. Brain Imaging Behav. 2018 Oct;12(5):1306-1317. doi: 10.1007/s11682-017-9800-1.
- Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teachingLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bernard LeFoll, M.D., Ph.D principal investigator
CAMH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing repetitive Transcranial Magnetic Stimulation in people with Healthy, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in [11C]-(+)-PHNO binding (time frame: Participants will complete all sessions in a period of approximately 4 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02212405, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2016.