- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05560113
Disrupting Fear-based Memory Consolidation
September 12, 2023 updated by: Michael R Borich, Emory University
Forgetting Fear: Establishing a Novel Non-invasive Approach to Disrupt Fear-based Sensory Memory Consolidation in Humans
This project represents a unique collaborative opportunity to pursue the essential proof-of-principle demonstration that non-invasive interference of sensory cortical memory consolidation shortly after an emotional experience can attenuate the cued fear response and potentially reduce the risk of developing post-traumatic stress disorder (PTSD).
If successful, the study results would anchor a potential advance in the treatment of patients after a traumatic event and seed future animal and clinical studies of emotional sensory cortical memory consolidation to reduce the prevalence and negative sequelae of PTSD.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
This mechanistic study in humans will study an unexplored precision-based approach of non-invasive neuromodulation of sensory cortex with the aim to prevent PTSD by attenuating the sensory encoding of fear memory.
The objective of this project is to explore the basic science and therapeutic potential of sensory-emotional reprogramming in humans, and translate this idea into a precise, individualized treatment to reduce the risk that negative emotional sensory experiences lead to PTSD.
Understanding sensory-emotional programming in humans could anchor a breakthrough in the treatment of patients after a traumatic event and seed future animal and clinical studies of emotional sensory cortical memory consolidation to reduce the prevalence and negative sequela of PTSD.
Study Type
Interventional
Enrollment (Estimated)
66
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Michael Borich, PhD
- Phone Number: 404-712-5512
- Email: michael.borich@emory.edu
Study Contact Backup
- Name: Jennifer Stevens, PhD
- Phone Number: 404-778-1698
- Email: jswils4@emory.edu
Study Locations
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Georgia
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Atlanta, Georgia, United States, 30322
- Recruiting
- Emory Rehabilitation Hospital
-
Contact:
- Michael Borich, PhD
- Phone Number: 404-712-0612
- Email: michael.borich@emory.edu
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Atlanta, Georgia, United States, 30322
- Recruiting
- Emory University Hospital
-
Contact:
- Michael Borich, PhD
- Phone Number: 404-712-0612
- Email: michael.borich@emory.edu
-
Contact:
- Robert C Liu, PhD
- Phone Number: 404-727-5274
- Email: robert.liu@emory.edu
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Ability to provide informed consent
- Willingness to participate in study
- No history of musculoskeletal impairment or neurological disease
- Clinical diagnosis of PTSD for individuals in the PTSD group.
Exclusion Criteria:
- Any participant outside the age range
- Participants that show signs of dementia (score < 20 on the Montreal Cognitive Assessment)
- Participants that have a history of major head trauma, a neurodegenerative disorder, or recent (<6 months) substance abuse;
- Participants that had a recent history of Central Nervous System (CNS) active drugs that may influence cortical excitability or learning; or
- Participants that report contraindications to TMS or MRI - if participating in the TMS/MRI experiments
- Current psychoactive medication usage
- Current symptoms of psychosis or bipolar disorder (as indicated by study staff through a clinical interview as part of that study).
- The study will exclude adults unable to consent, individuals who are not yet adults, pregnant women and prisoners on scientific grounds and to minimize risk.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: cTBS: Inhibitory Transcranial magnetic stimulation (TMS) to sensory Cortex
Participants will undergo a Functional magnetic resonance imaging (fMRI) scan while performing a fear conditioning/extinction task at the Center for Systems Imaging- Emory University Hospital (CSI-EUH) and then either stay at CSI-EUH or relocate to the Neural Plasticity Research Laboratory at Emory Rehabilitation Hospital.
Participants will then be randomly assigned to either receive active or sham continuous theta burst stimulation (cTBS) to transiently disrupt neural activity in the targeted sensory cortex region specifically during the sensory memory consolidation window.
|
cTBS, a patterned form of TMS, (80% active motor threshold intensity, 3 pulses at 50Hz, 200ms interval, 600 pulses, 40s duration applied over the targeted sensory cortical region using real-time neuronavigation to focally and transiently inhibit neural activity
|
Placebo Comparator: Sham cTBS
Participants will undergo a Functional magnetic resonance imaging (fMRI) scan while performing a fear conditioning/extinction task at CSI-EUH and then either stay at CSI-EUH or relocate to the Neural Plasticity Research Laboratory at Emory Rehabilitation Hospital.
Participants will then be randomly assigned to either receive active or sham continuous theta burst stimulation (cTBS) to transiently disrupt neural activity in the targeted sensory cortex region specifically during the sensory memory consolidation window.
|
This will be a sham intervention.
An active/sham stimulating coil will be used for double-blinding of stimulation condition.
cTBS is safe and has established safety guidelines that will be strictly adhered to during study conduction.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Neural Connections: Functional network connectivity
Time Frame: Study Day 30 and Day 31
|
Preprocessing of neuroimaging data will be conducted using fMRI prep.
Pre-processed neuroimaging data will undergo first and second level modeling in Statistical Parametric Mapping.
First level analysis include an event-related model with the onset and duration of each event included for each condition, and motion included as a regressor.
A high-pass filter of 128s will be applied to account for low-frequency drifts.
Amygdala regions of interest (ROIs) will be defined anatomically using California Institute of Technology (CIT168) Subcortical Atlas.
Primary sensory cortex ROI & seed coordinates will be defined utilizing voxels within a V1 region mask showing maximal functional connectivity with the amygdala during conditioning.
|
Study Day 30 and Day 31
|
Changes in Neural Connections: Regional activation
Time Frame: Study Day 30 and 31
|
Preprocessing of neuroimaging data will be conducted using fMRI prep.
Pre-processed neuroimaging data will undergo first and second level modeling in Statistical Parametric Mapping.
First level analysis include an event-related model with the onset and duration of each event included for each condition, and motion included as a regressor.
A high-pass filter of 128s will be applied to account for low-frequency drifts.
Whole-brain analysis of changes in local regions of activity will be measured by change in blood-oxygen-level-dependent (BOLD) signal from resting activity.
Multiple comparisons using permutation-based methods to control the false positive rate to p<.05.
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Study Day 30 and 31
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Measures of skin conductive response
Time Frame: Study Day 30 and Day 31
|
Skin conductance response (SCR) will be recorded during localization, conditioning, and fear retention tasks using the BIOPAC system MP150 (BIOPAC systems, Inc.) and parameters previously utilized in the lab.
SCR is a validated physiological measure of sympathetic arousal, with higher SCR indicating a higher arousal response to conditioned stimuli.
Change in SCR from early to late extinction is our primary indicator of the degree of extinction learning.
SCR will be scored as a response to individual Conditioned Stimulus (CS)+E and CS- stimuli (maximum SC within 6 seconds post-CS onset, minus average SC over a 2-second prestimulus baseline) and will be square-root transformed for normalization.
Early fear extinction will be defined as occurring within the first fear extinction run, with late fear extinction being defined as the second extinction run.
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Study Day 30 and Day 31
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ECG
Time Frame: Study Day 31
|
Heart rate and heart-rate variability (HRV) will be measured using the ECG module of the BIOPAC system at a sampling rate of 1 kilo Hertz (kHz).
One 5mm Ag/AgCl (Silver/Silver Chloride) electrode will be placed on the chest above the right clavicle, another electrode will be placed on the chest under the left side of the ribcage.
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Study Day 31
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Acoustic Startle response
Time Frame: Study Day 31
|
The acoustic startle response (eyeblink component) will be measured via electriomyography (EMG) of the right orbicularis oculi muscle.
Two 5 mm Ag/AgCl pre-gelled disposable electrodes will be positioned approximately 1 cm under the pupil and 1 cm below the lateral canthus.
The startle probe (noise burst) will be a 108-decibel (dB) (A) Sound Pressure Level (SPL), 40-ms burst of broadband noise with a near instantaneous rise time .
The startle probe is a white noise burst that is affectively neutral and clearly differentiable from the aversive sound used for the US.
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Study Day 31
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Changes in Fear conditioning and extinction task
Time Frame: Study Day 30 and Day 31
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Participants will view pictures of animals and tools which will not be repeated.
During the 1st phase, 3 categories of images will be displayed: animals, tools, and animal/tool images phase-scrambled.
Blocks of 10 images of each category will be displayed 4 times, with each image displayed for 0.75 seconds with a 0.25 s delay between images and 11 s inter-block interval.
This task will allow for localization of brain areas activated by animal images vs. tool images, with the phase scrambled images serving as a control.
15 animal and 15 tool images will be randomly displayed for 4.5 s with a fixation cross displayed between each image for 6, 8, or 10 seconds.
For the 2nd phase, 10 of either the animal or tool images are assigned as the CS+, and paired with the US, a 1-second loud screeching sound at the end of the image presentation.
The other image type, the CS-, will not be paired with the US.
In the fear retention phase on Day 2, the CS+ and CS- will be presented without the US.
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Study Day 30 and Day 31
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Michael Borich, PhD, Emory University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 28, 2022
Primary Completion (Estimated)
December 1, 2028
Study Completion (Estimated)
December 1, 2028
Study Registration Dates
First Submitted
September 15, 2022
First Submitted That Met QC Criteria
September 26, 2022
First Posted (Actual)
September 29, 2022
Study Record Updates
Last Update Posted (Actual)
September 14, 2023
Last Update Submitted That Met QC Criteria
September 12, 2023
Last Verified
September 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- STUDY00004510
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
Raw and preprocessed magnetic resonance imaging data as well as behavioral data.
IPD Sharing Time Frame
Data will be made available after completion of primary data analyses.
IPD Sharing Access Criteria
: Data will be made publicly available using a data archive (e.g., IPD Sharing Statement LONI Laboratory of Neuro Imaging (LONI), ida.loni.usc.edu) for potential big data analyses as well as reproducibility analyses
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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