Effects of Connectivity-based rTMS and State-Dependency on Amygdala Activation

NCT ID: NCT03746405

Last Updated: 2020-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-16
• Study Completion Date: 2020-01-31

Brief 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 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Repetitive TMS (rTMS)

excitatory rTMS applied over the medial prefrontal cortex (fMRI-guided)

Group Type: ACTIVE_COMPARATOR

repetitive transcranial magnetic stimulation

Intervention Type: DEVICE

excitatory 5Hz rTMS will be used

Sham repetitive TMS (rTMS)

electrical sham coil applied over the medial prefrontal cortex (fMRI-guided)

Group Type: SHAM_COMPARATOR

Sham repetitive transcranial magnetic stimulation

Intervention Type: DEVICE

an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used

Interventions

repetitive transcranial magnetic stimulation

excitatory 5Hz rTMS will be used

Intervention Type: DEVICE

Sham repetitive transcranial magnetic stimulation

an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lysianne Beynel, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Pro00101172

Identifier Type: -

Identifier Source: org_study_id