Threat Reversal Abnormality in Patients With Anxiety Disorders

NCT ID: NCT06232369

Last Updated: 2024-02-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 190 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-31
• Study Completion Date: 2025-09-30

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. 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. The neural mechanism underlying threat reversal abnormalities in patients with anxiety disorders is hypothesized to involve the prefrontal cortex, amygdala, and hippocampus.

3. The repetitive stimulation to the core brain regions of threat reversal is assumed to improve threat reversal abilities and anxiety symptoms of patients.

Detailed Description

In this study, there are three sub-trials in combination with skin conductance response (SCR), functional magnetic resonance imaging (fMRI), and non-invasive neuromodulation techniques to uncover the abnormal threat reversal in anxiety disorder at behavioral and neural levels.

Participants in the first trial will learn the threat of emotional faces based on the Pavlovian conditioned fear learning paradigm; their neural activities in the hypothesized brain regions will be obtained via brain imaging equipment. The researchers will compare the differences among three groups (one patient group, two healthy control groups with different anxiety level) on performance in the threat reversal task, and their neural activities and brain functional connectivity characteristics, in order to reveal the potential behavioral threat reversal abnormalities and core associated brain regions underlying threat reversal.

Participants in the second trial will be given the same learning paradigm and brain imaging equipment as in the first, but with repetitive stimulation intervention on the core brain regions determined in study 1. Using a double-blind randomized controlled experiment, the participants will be divided into three groups (active stimulation + patient, sham stimulation + patient, and sham stimulation + healthy control). The researchers will compare the behavioral differences in the threat reversal task after active and sham stimulation.

Participants in the third trial will be given the same study design and intervention as the second trial, but for eight weeks. Finally, the researchers will retest and compare the improvement in threat reversal abilities and anxiety symptoms to see the long-term clinical effects of the intervention.

Conditions

Anxiety Disorder; Anxiety State

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Patient group + active stimulation intervention

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.

Group Type: EXPERIMENTAL

Active repetitive deep transcranial magnetic stimulation (dTMS)

Intervention Type: 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 + sham stimulation intervention

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.

Group Type: SHAM_COMPARATOR

Sham repetitive deep transcranial magnetic stimulation (dTMS)

Intervention Type: 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

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

Group Type: SHAM_COMPARATOR

Sham repetitive deep transcranial magnetic stimulation (dTMS)

Intervention Type: 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.

Interventions

Active repetitive deep transcranial magnetic stimulation (dTMS)

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.

Intervention Type: DEVICE

Sham repetitive deep transcranial magnetic stimulation (dTMS)

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.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

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)

1. No physical diseases or mental disorders.

2. No claustrophobia.

3. No hereditary diseases.

4. No medication history or smoking history.

5. Females not pregnant and not in their menstrual period.

6. Normal vision or corrected vision, no smoking, drinking alcohol, or taking medication within 24 hours prior to the experiment.

7. No previous participation in similar experiments.

Exclusion Criteria

1. A history of serious cardiovascular, cerebrovascular diseases, stroke, or other neurological disorders, a history of gastrointestinal diseases.

2. Severe hearing or vision impairments.

3. Metallic implants in the body, such as non-removable dentures, stents, metal plates, joint metal replacements, etc.

4. Claustrophobia.

5. Acute or chronic diseases or infections.

6. Pregnancy or breastfeeding.

7. Smoking or drinking alcohol within 24 hours before the experiment.

8. Previous participation in similar experiments conducted by this institution.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The National Natural Science Foundation of China (NSFC)

UNKNOWN

Sponsor Role: collaborator

Shenzhen Kangning Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jingchu Hu

Associate Research Fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jingchu Hu, Dr.

Role: PRINCIPAL_INVESTIGATOR

Shenzhen Kangning Hospital

Central Contacts

Jingchu Hu, Dr.

Role: CONTACT

hujingchu@gmail.com

(+86)15603072635

Other Identifiers

82201672

Identifier Type: -

Identifier Source: org_study_id