Threat Reversal Abnormality in Patients With Anxiety Disorders

NCT06232369 | Not Yet Recruiting

• 1 other identifier: 82201672
• Study Type: interventional
• Target: 190
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to explore the flexibility of threat control and underlying neural mechanism based on the threat reversal paradigm (a highly validated new paradigm where threat learning and inhibition are required) in patients with anxiety disorders (mainly generalized anxiety disorder). The hypotheses are:

1. 1.Threat reversal abilities are hypothesized to be impaired in patients with anxiety disorders compared to healthy normal subjects, which are assumed to be associated with anxiety symptoms.
2. 2.The neural mechanism underlying threat reversal abnormalities in patients with anxiety disorders is hypothesized to involve the prefrontal cortex, amygdala, and hippocampus.
3. 3.The repetitive stimulation to the core brain regions of threat reversal is assumed to improve threat reversal abilities and anxiety symptoms of patients.

Conditions

Anxiety Disorder; Anxiety State

Keywords

Threat Reversal; Emotion Flexibility

Outcome Measures

Primary Outcomes (4)

• Changes in participants' skin conductance response (SCR)

  The level of SCR will be assessed for each experiment trial as the base-to-peak amplitude difference in skin conductance of the largest deflection (in micro-siemens; pS) in the 0.5-4.5-slatency window after stimulus onset.

  Baseline; every week (assessed weekly up to 8 weeks from the date of last intervention session)

• Changes in the prefrontal cortex measured with fMRI

  Changes in the difference in blood oxygenation level dependent (BOLD) signals in the prefrontal cortex before and after the intervention.

  Baseline; once per week (assessed weekly up to 8 weeks from the date of last intervention session)

• Changes in the amygdala measured with fMRI

  Changes in the difference in blood oxygenation level dependent (BOLD) signals in the amygdala before and after the intervention.

  Baseline; once per week (assessed weekly up to 8 weeks from the date of last intervention session)

• Changes in the hippocampus measured with fMRI

  Changes in the difference in blood oxygenation level dependent (BOLD) signals in the hippocampus before and after the intervention.

  Baseline; once per week (assessed weekly up to 8 weeks from the date of last intervention session)

Secondary Outcomes (3)

• Changes in the State-Trait Anxiety Scale (STAI)

  Baseline; once per week (assessed weekly up to 8 weeks from the date of last intervention session); 3 months (assessed at the week after 3 months from the last intervention session)

• Changes in the Intolerance of Uncertainty Scale-12 (IUS-12)

  Baseline; once per week (assessed weekly up to 8 weeks from the date of last intervention session); 3 months (assessed at the week after 3 months from the last intervention session)

• Changes in the Anxiety Sensitivity Index (ASI)

  Baseline; once per week (assessed weekly up to 8 weeks from the date of last intervention session); 3 months (assessed at the week after 3 months from the last intervention session)

Study Arms (3)

Patient group + active stimulation intervention

EXPERIMENTAL

Patient participants with anxiety disorders in this arm will first accept active repetitive stimulation on core brain regions and then complete the threat reversal learning paradigm.

Device: Active repetitive deep transcranial magnetic stimulation (dTMS)

Patient group + sham stimulation intervention

SHAM COMPARATOR

Patient participants with anxiety disorders in this arm will first accept sham repetitive stimulation on core brain regions and then complete the threat reversal learning paradigm.

Device: Sham repetitive deep transcranial magnetic stimulation (dTMS)

Healthy control group + sham stimulation intervention

SHAM COMPARATOR

Healthy participants in this arm will first accept sham repetitive stimulation on core brain regions and then complete the threat reversal learning paradigm.

Device: Sham repetitive deep transcranial magnetic stimulation (dTMS)

Interventions

Active repetitive deep transcranial magnetic stimulation (dTMS) DEVICE

Before the intervention, the brain structure of each participant will be captured using an MRI scanner, and individualized spatial coordinates of the hypothesized target will be determined based on these 3D structural images. Then the resting motor threshold will be tested using the method of thumb twitching observation. The intervention will employ the H7 coil that is accurately delivered to the intended target by an optic navigation and a deep pulse protocol at 90% of the tested threshold for 15-minute stimulation duration.

Patient group + active stimulation intervention

Sham repetitive deep transcranial magnetic stimulation (dTMS) DEVICE

Before the intervention, the brain structure of each participant will be captured using an MRI scanner, and individualized spatial coordinates of the hypothesized target will be determined based on these 3D structural images. Then the resting motor threshold will be tested using the method of thumb twitching observation. The intervention will employ the H7 coil that is placed on the scalp to mimic the sensation and sounds of the actual treatment but without letting the magnetic field reach the brain tissue for 15-minute duration.

Healthy control group + sham stimulation intervention; Patient group + sham stimulation intervention

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of anxiety disorders (by psychiatrists using the structured clinical interview for DSM-IV-TR (SCID) with reference to the diagnostic criteria for GAD according to the ICD-10)

You may not qualify if:

• A history of serious cardiovascular, cerebrovascular diseases, stroke, or other neurological disorders, a history of gastrointestinal diseases.
• Severe hearing or vision impairments.
• Metallic implants in the body, such as non-removable dentures, stents, metal plates, joint metal replacements, etc.
• Claustrophobia.
• Acute or chronic diseases or infections.
• Pregnancy or breastfeeding.
• Smoking or drinking alcohol within 24 hours before the experiment.
• Previous participation in similar experiments conducted by this institution.
• No physical diseases or mental disorders.
• No claustrophobia.
• No hereditary diseases.
• No medication history or smoking history.
• Females not pregnant and not in their menstrual period.
• Normal vision or corrected vision, no smoking, drinking alcohol, or taking medication within 24 hours prior to the experiment.
• No previous participation in similar experiments.

Sponsors & Collaborators

• Shenzhen Kangning Hospital: lead
• The National Natural Science Foundation of China (NSFC): collaborator

MeSH Terms

Conditions

Anxiety Disorders

Condition Hierarchy (Ancestors)

Mental Disorders

Study Officials

• Jingchu Hu, Dr.

  Shenzhen Kangning Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jingchu Hu, Dr.

CONTACT

(+86)15603072635; hujingchu@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Research Fellow

Study Record Dates

• First Submitted: January 10, 2024
• First Posted: January 30, 2024
• Study Start: March 1, 2024
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: February 6, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The information will be shared after the related paper is published and will be available for at least one year.
• Access Criteria: The information will be shared on the Open Science Framework for the public.