Neuromodulation of the Fear Extinction Circuit Using Temporally and Anatomically Specific TMS in Humans

PTSD Clinical Trial

Official title:

Neuromodulation of the Fear Extinction Circuit Using Temporally and Anatomically Specific TMS in Humans

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05368987
• Other study ID #: 21-00498
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2022
• Est. completion date: September 30, 2026

Study information

• Verified date: April 2023
• Source: NYU Langone Health
• Contact: Mohammed Milad, MD
• Phone: 646-754-7406
• Email: mohammed.milad[@]nyulangone.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to explore the mechanisms of how transcranial magnetic stimulation (TMS) impacts fear circuits. The overarching objectives are to understand how varying TMS parameters affect targeted brain regions in order to optimize its impact on enhancing fear extinction memory consolidation in a population with known fear extinction deficiencies: post-traumatic stress disorder (PTSD). 250 subjects will take part in this research study across NYU Langone Health. The study will include preliminary screenings, baseline visits, and experimental visits across four days

Description:

The experiments proposed are aimed to understand how timing and location of transcranial magnetic stimulation (TMS) in humans will impact their ability to reduce conditioned fear responses and impact the activation of their brain regions involved in fear regulation. The researchers will use a novel TMS approach to vary timing and location of its delivery so that the researchers can characterize and establish best time and location to obtain optimal impact on fear inhibition, and then test these parameters in PTSD patients and see if such can rescue extinction deficits in PTSD. The anticipated impact is to enhance our understanding of the neural mechanisms of associated with TMS use and explore potential novel approaches for advancing PTSD treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: September 30, 2026
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 18 - 70 years of age

• Right-handed (Edinburgh Inventory - Oldfield 1971)

• To be balanced for age, gender, and years of education, as well as self-identified race/ethnicity.

• Inclusion Criteria: PTSD Subjects

• Diagnosis of primary PTSD (as determined by SCID)

• Inclusion Criteria: Healthy Controls (HC)

• SCID diagnosis consistent with no current or past history of Axis I psychiatric disorders.

• Willing and able to provide informed consent

Exclusion Criteria:

• Current alcohol or substance use disorder (within the past 6 months)

• Lifetime history of seizure or significant head trauma (i.e., extended loss of consciousness, neurological sequelae, or known structural brain lesion) or other significant neurologic disease

• Lifetime history of psychosis, bipolar disorder, tic disorder, or eating disorder is excluded. Past and current unipolar mood disorders without psychosis and anxiety disorders will be allowed so long as they are not primary and not associated with psychosis.

• Use of psychotropic medication within 4 weeks prior to study (within 6 weeks for fluoxetine, or other long-lived compounds; within one year for neuroleptics).

• Pregnancy (to be ruled out by urine ß-HCG).

• Metallic implants or devices contraindicating magnetic resonance imaging.

• Currently taking medications that lower the seizure threshold. These include antipsychotics, high dose theophylline or stimulants such as methylphenidate. Patients taking bupropion must be on a stable dose *last 3 months) and take less than or equal to 300 mg/day.

• Implanted devices in subject's head (shunts, cochlear implants); metal in subject's head (other than dental implants).

Related Conditions & MeSH terms

• PTSD

Intervention

Device:
• Transcranial magnetic stimulation (TMS)
Research subjects will undergo non-invasive TMS, with a frequency of 20Hz and intensity of 120% of their resting motor threshold (rMT) at varying time points and locations.

Locations

Country	Name	City	State
United States	NYU Langone Health	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
NYU Langone Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Skin Conductance Response (SCR)	Conductance is measured by placing two electrodes next to the skin and passing a tiny electric charge between the two points. SCR is proportionally related to the number of sweat glands that are activated, meaning in essence that the more emotionally aroused an individual is, the more the SCR amount is increased.	Baseline
Primary	Skin Conductance Response (SCR)	Conductance is measured by placing two electrodes next to the skin and passing a tiny electric charge between the two points. SCR is proportionally related to the number of sweat glands that are activated, meaning in essence that the more emotionally aroused an individual is, the more the SCR amount is increased.	Experimental Day 1
Primary	Skin Conductance Response (SCR)	Conductance is measured by placing two electrodes next to the skin and passing a tiny electric charge between the two points. SCR is proportionally related to the number of sweat glands that are activated, meaning in essence that the more emotionally aroused an individual is, the more the SCR amount is increased.	Experimental Day 2
Primary	Skin Conductance Response (SCR)	Conductance is measured by placing two electrodes next to the skin and passing a tiny electric charge between the two points. SCR is proportionally related to the number of sweat glands that are activated, meaning in essence that the more emotionally aroused an individual is, the more the SCR amount is increased.	Experimental Day 3
Primary	Blood Oxygen Levels	fMRI data, including blood-oxygen-level-dependent (BOLD) responses, is used in neuroimaging studies assess neural correlate activations and observe the increase/decrease in activation of a particular brain area in response to a specific cue. When these cells are active, there is an increase in blood oxygen in the surrounding area.	Experimental Day 3
Secondary	Score on Patient Health Questionnaire (PHQ-9)	PHQ-9 is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. The participant will self-report how often he/she has been bothered by 9 problems over the last 2 weeks. The total score range is 0-27. A PHQ-9 score total of 0-4 points equals "normal" or minimal depression. Scoring between 5-9 points indicates mild depression, 10-14 points indicates moderate depression, 15-19 points indicates moderately severe depression, and 20 or more points indicates severe depression.	Baseline
Secondary	Score on Patient Health Questionnaire (PHQ-9)	PHQ-9 is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. The participant will self-report how often he/she has been bothered by 9 problems over the last 2 weeks. The total score range is 0-27. A PHQ-9 score total of 0-4 points equals "normal" or minimal depression. Scoring between 5-9 points indicates mild depression, 10-14 points indicates moderate depression, 15-19 points indicates moderately severe depression, and 20 or more points indicates severe depression.	Experimental Day 1
Secondary	Score on Patient Health Questionnaire (PHQ-9)	PHQ-9 is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. The participant will self-report how often he/she has been bothered by 9 problems over the last 2 weeks. The total score range is 0-27. A PHQ-9 score total of 0-4 points equals "normal" or minimal depression. Scoring between 5-9 points indicates mild depression, 10-14 points indicates moderate depression, 15-19 points indicates moderately severe depression, and 20 or more points indicates severe depression.	Experimental Day 2
Secondary	Score on Patient Health Questionnaire (PHQ-9)	PHQ-9 is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. The participant will self-report how often he/she has been bothered by 9 problems over the last 2 weeks. The total score range is 0-27. A PHQ-9 score total of 0-4 points equals "normal" or minimal depression. Scoring between 5-9 points indicates mild depression, 10-14 points indicates moderate depression, 15-19 points indicates moderately severe depression, and 20 or more points indicates severe depression.	Experimental Day 3
Secondary	Score on State-Trait Anxiety Inventory (STAI) - Form Y1	STAI - Form Y1 is a commonly used measure of trait and state anxiety that consists of 20 statement which people have used to describe themselves. Each statement is scored from 1 (Not at all) to 4 (very much so). The total score range is 20-80; STAI scores are commonly classified as "no or low anxiety" (20-37), "moderate anxiety" (38-44), and "high anxiety" (45-80).	Baseline
Secondary	Score on State-Trait Anxiety Inventory (STAI) - Form Y1	STAI - Form Y1 is a commonly used measure of trait and state anxiety that consists of 20 statement which people have used to describe themselves. Each statement is scored from 1 (Not at all) to 4 (very much so). The total score range is 20-80; STAI scores are commonly classified as "no or low anxiety" (20-37), "moderate anxiety" (38-44), and "high anxiety" (45-80).	Experimental Day 1
Secondary	Score on State-Trait Anxiety Inventory (STAI) - Form Y1	STAI - Form Y1 is a commonly used measure of trait and state anxiety that consists of 20 statement which people have used to describe themselves. Each statement is scored from 1 (Not at all) to 4 (very much so). The total score range is 20-80; STAI scores are commonly classified as "no or low anxiety" (20-37), "moderate anxiety" (38-44), and "high anxiety" (45-80).	Experimental Day 2
Secondary	Score on State-Trait Anxiety Inventory (STAI) - Form Y1	STAI - Form Y1 is a commonly used measure of trait and state anxiety that consists of 20 statement which people have used to describe themselves. Each statement is scored from 1 (Not at all) to 4 (very much so). The total score range is 20-80; STAI scores are commonly classified as "no or low anxiety" (20-37), "moderate anxiety" (38-44), and "high anxiety" (45-80).	Experimental Day 3
Secondary	Score on Intolerance of Uncertainty Scale (IUS-12) - Short Form	IUS-12 is a 12-item self-report questionnaire where items are rated on 5-point Likert scales. IUS-12 is based on a definition of general uncertainty-related reactions that may be present in different anxiety disorders. Each item is scored from 1 (not at all characteristic of me) to 5 (entirely characteristic of me). The total score range is 12-60; the higher the score, the greater the intolerance of uncertainty.	Baseline
Secondary	Score on Intolerance of Uncertainty Scale (IUS-12) - Short Form	IUS-12 is a 12-item self-report questionnaire where items are rated on 5-point Likert scales. IUS-12 is based on a definition of general uncertainty-related reactions that may be present in different anxiety disorders. Each item is scored from 1 (not at all characteristic of me) to 5 (entirely characteristic of me). The total score range is 12-60; the higher the score, the greater the intolerance of uncertainty.	Experimental Day 1
Secondary	Score on Intolerance of Uncertainty Scale (IUS-12) - Short Form	IUS-12 is a 12-item self-report questionnaire where items are rated on 5-point Likert scales. IUS-12 is based on a definition of general uncertainty-related reactions that may be present in different anxiety disorders. Each item is scored from 1 (not at all characteristic of me) to 5 (entirely characteristic of me). The total score range is 12-60; the higher the score, the greater the intolerance of uncertainty.	Experimental Day 2
Secondary	Score on Intolerance of Uncertainty Scale (IUS-12) - Short Form	IUS-12 is a 12-item self-report questionnaire where items are rated on 5-point Likert scales. IUS-12 is based on a definition of general uncertainty-related reactions that may be present in different anxiety disorders. Each item is scored from 1 (not at all characteristic of me) to 5 (entirely characteristic of me). The total score range is 12-60; the higher the score, the greater the intolerance of uncertainty.	Experimental Day 3
Secondary	Score on Childhood Trauma Questionnaire (CTQ)	CTQ consists of 28 items scored from 1 (never true) to 5 (very often true). The questions ask the participant about some of his/her experiences growing up as a child and a teenager. The total score range is 28-140; the higher the score, the greater the childhood trauma.	Baseline
Secondary	Score on Childhood Trauma Questionnaire (CTQ)	CTQ consists of 28 items scored from 1 (never true) to 5 (very often true). The questions ask the participant about some of his/her experiences growing up as a child and a teenager. The total score range is 28-140; the higher the score, the greater the childhood trauma.	Experimental Day 1
Secondary	Score on Childhood Trauma Questionnaire (CTQ)	CTQ consists of 28 items scored from 1 (never true) to 5 (very often true). The questions ask the participant about some of his/her experiences growing up as a child and a teenager. The total score range is 28-140; the higher the score, the greater the childhood trauma.	Experimental Day 2
Secondary	Score on Childhood Trauma Questionnaire (CTQ)	CTQ consists of 28 items scored from 1 (never true) to 5 (very often true). The questions ask the participant about some of his/her experiences growing up as a child and a teenager. The total score range is 28-140; the higher the score, the greater the childhood trauma.	Experimental Day 3