Amygdala ActivationConnecTMSNCT03746405
Effects of Connectivity-based rTMS and State-Dependency on Amygdala Activation
A study testing repetitive transcranial magnetic stimulation in people with Amygdala Activation, run by Duke University at 1 site in United States.
Trial summary
Posttraumatic stress disorder (PTSD) is a highly debilitating disease with response rates to pharmacological treatment rarely exceeding 60%. Preliminary attempts have been made to use repetitive transcranial magnetic stimulation (rTMS) as a non-pharmacological treatment alternative, but thus far rTMS approaches have… Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Amygdala Activation
- 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
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jun 2019to 31 Jan 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age Restrictions: Young Group (from 18 to 35 years old)
- Use of effective method of birth control for women of childbearing capacity.
- Willing to provide informed consent.
Who cannot join
- Current or recent (within the past 6 months) history of substance abuse or dependence.
- Current serious medical illness.
- History of seizure, epilepsy, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion, devices that may be affected by rTMS or MRI (pacemaker, medication pump, cochlear implant, implanted brain stimulator)
- Inability or unwilling to give informed consent.
- Diagnosed any Axis I DSM-IV disorder (MINI, DSM-IV).
- Clinically defined neurological disorder.
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- Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure, or currently taking medication that lowers the seizure threshold.
- Claustrophobia (MRI scanner).
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27705
About this study
Posttraumatic stress disorder (PTSD) is a highly debilitating disease with response rates to pharmacological treatment rarely exceeding 60%. Preliminary attempts have been made to use repetitive transcranial magnetic stimulation (rTMS) as a non-pharmacological treatment alternative, but thus far rTMS approaches have demonstrated only modest efficacy. A major factor contributing to these limited effects stems from the depth penetration of TMS, which is not sufficient to directly modulate deep subcortical structures, such as the amygdala, that are affected in PTSD. Moreover, while rTMS effects have been shown to be state-dependent, (i.e. vary substantially according to the neural state during stimulation), this important factor is rarely considered during the clinical application of rTMS. The current study addresses both of these limitations to improve the therapeutic efficacy of rTMS for PTSD. Here we will develop a protocol to test if connectivity-based rTMS is able to modulate amygdala activity through the functional connections with medial prefrontal cortex, taking advantage of state-dependency to enhance rTMS effects by actively engaging the amygdala through a fear perception task. BOLD activation in the amygdala and its connectivity with the frontal cortex will constitute the primary outcomes to test rTMS efficacy. Heart rate variability and skin galvanic responses, acquired during the presentation of fearful faces, will be used as continuous moderators of task engagement during rTMS. If successful, this study will pave the way for a large-scale study to investigate whether state-dependent, connectivity-based rTMS of the amygdala can improve rTMS efficacy as a clinical treatment for PTSD.
- Conditions
- Amygdala Activation
- Being tested
- repetitive transcranial magnetic stimulation, Sham repetitive transcranial magnetic stimulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
repetitive transcranial magnetic stimulationDevice
excitatory 5Hz rTMS will be used
Sham repetitive transcranial magnetic stimulationDevice
an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used
| Study group | Role | What they receive |
|---|---|---|
| Repetitive TMS (rTMS) | Active comparator | excitatory rTMS applied over the medial prefrontal cortex (fMRI-guided) Receives: Device: repetitive transcranial magnetic stimulation |
| Sham repetitive TMS (rTMS) | Sham comparator | electrical sham coil applied over the medial prefrontal cortex (fMRI-guided) Receives: Device: Sham repetitive transcranial magnetic stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute Effect of a rTMS Session on Brain Activation as Measured by the Cerebral Blood Flow (Blood Oxygenation Level Dependent Signal)
Blood oxygenation level dependent (BOLD) will be assessed to evaluate the acute effect of rTMS applied over the medial prefrontal cortex on the amygdala activation.
This outcome (expressed a z-score) represents the amygdala activation, either after active rTMS or after sham rTMS.
Higher z-scores for active than for sham rTMS indicates that amygdala activity increases after active rTMS compared to sham rTMS, on the other hand lower z-score after active rTMS vs. after Sham rTMS indicated that the amygdala activity would have been reduced with active rTMS.
Measured: right after the rTMS session, up to one hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2018
- Study start16 Jun 2019
- Primary completion31 Jan 2020
- Study completion31 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Amygdala ActivationStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- 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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lysianne Beynel, PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03746405
- Sponsor's protocol ID
- Pro00101172
- Acronym
- ConnecTMS
- Status last verified
- Dec 2020
- First submitted
- 16 Nov 2018
- Last updated
- 10 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Connectivity-based rTMS and State-Dependency on Amygdala Activation
- ClinicalTrials.gov ID
- NCT03746405
- Acronym / sponsor ID
- ConnecTMS / Pro00101172
- Conditions
- Amygdala Activation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- 16 Jun 2019 (actual)
- Primary completion
- 31 Jan 2020 (actual)
- Study completion
- 31 Jan 2020 (actual)
- First posted
- 19 Nov 2018 (actual)
- Results
- Posted 5 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Posttraumatic stress disorder (PTSD) is a highly debilitating disease with response rates to pharmacological treatment rarely exceeding 60%. Preliminary attempts have been made to use repetitive transcranial magnetic stimulation (rTMS) as a non-pharmacological treatment alternative, but thus far rTMS approaches have demonstrated only modest efficacy. A major factor contributing to these limited effects stems from the depth penetration of TMS, which is not sufficient to directly modulate deep subcortical structures, such as the amygdala, that are affected in PTSD. Moreover, while rTMS effects have been shown to be state-dependent, (i.e. vary substantially according to the neural state during stimulation), this important factor is rarely considered during the clinical application of rTMS. The current study addresses both of these limitations to improve the therapeutic efficacy of rTMS for PTSD. Here we will develop a protocol to test if connectivity-based rTMS is able to modulate amygdala activity through the functional connections with medial prefrontal cortex, taking advantage of state-dependency to enhance rTMS effects by actively engaging the amygdala through a fear perception task. BOLD activation in the amygdala and its connectivity with the frontal cortex will constitute the primary outcomes to test rTMS efficacy. Heart rate variability and skin galvanic responses, acquired during the presentation of fearful faces, will be used as continuous moderators of task engagement during rTMS. If successful, this study will pave the way for a large-scale study to investigate whether state-dependent, connectivity-based rTMS of the amygdala can improve rTMS efficacy as a clinical treatment for PTSD.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Repetitive TMS (rTMS) | Active comparator | Device: repetitive transcranial magnetic stimulationexcitatory rTMS applied over the medial prefrontal cortex (fMRI-guided) |
| Sham repetitive TMS (rTMS) | Sham comparator | Device: Sham repetitive transcranial magnetic stimulationelectrical sham coil applied over the medial prefrontal cortex (fMRI-guided) |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Age Restrictions: Young Group (from 18 to 35 years old)
- Use of effective method of birth control for women of childbearing capacity.
- Willing to provide informed consent.
Key exclusion criteria (9 listed)
- Current or recent (within the past 6 months) history of substance abuse or dependence.
- Current serious medical illness.
- History of seizure, epilepsy, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion, devices that may be affected by rTMS or MRI (pacemaker, medication pump, cochlear implant, implanted brain stimulator)
- Inability or unwilling to give informed consent.
- Diagnosed any Axis I DSM-IV disorder (MINI, DSM-IV).
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 stimulationexcitatory 5Hz rTMS will be used | Device | Repetitive TMS (rTMS) |
| Sham repetitive transcranial magnetic stimulationan electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used | Device | Sham repetitive TMS (rTMS) |
Primary outcome
Acute Effect of a rTMS Session on Brain Activation as Measured by the Cerebral Blood Flow (Blood Oxygenation Level Dependent Signal)
Time frame: right after the rTMS session, up to one hour
Blood oxygenation level dependent (BOLD) will be assessed to evaluate the acute effect of rTMS applied over the medial prefrontal cortex on the amygdala activation. This outcome (expressed a z-score) represents the amygdala activation, either after active rTMS or after sham rTMS. Higher z-scores for active than for sham rTMS indicates that amygdala activity increases after active rTMS compared to sham rTMS, on the other hand lower z-score after active rTMS vs. after Sham rTMS indicated that the amygdala activity would have been reduced with active rTMS.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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.
Lysianne Beynel, PhD principal investigator
Duke University
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 Amygdala Activation, run by Duke University at 1 site in United States.
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 3 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 10 Dec 2020. 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 United States. 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?
Yes. Results are posted in the registry (first posted 5 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Acute Effect of a rTMS Session on Brain Activation as Measured by the Cerebral Blood Flow (Blood Oxygenation Level Dependent Signal) (time frame: right after the rTMS session, up to one hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Dec 2020.