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

NCT03746405 | Completed Results DMC FDA Device

• 1 other identifier: Pro00101172
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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.

  right after the rTMS session, up to one hour

Study Arms (2)

Repetitive TMS (rTMS)

ACTIVE COMPARATOR

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

Device: repetitive transcranial magnetic stimulation

Sham repetitive TMS (rTMS)

SHAM COMPARATOR

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

Device: Sham repetitive transcranial magnetic stimulation

Interventions

repetitive transcranial magnetic stimulation DEVICE

excitatory 5Hz rTMS will be used

Repetitive TMS (rTMS)

Sham repetitive transcranial magnetic stimulation DEVICE

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

Sham repetitive TMS (rTMS)

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Interventions

Transcranial Magnetic Stimulation

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Results Point of Contact

• Title: Dr Lysianne Beynel
• Organization: Duke University

lysianne.beynel@duke.edu

919-681-1157

Study Officials

• Lysianne Beynel, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: November 19, 2018
• Study Start: June 16, 2019
• Primary Completion: January 31, 2020
• Study Completion: January 31, 2020
• Last Updated: December 10, 2020
• Results First Posted: November 5, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)