A New Neuroregulatory Technology for the Therapy of AN Based on the Pathological Neural Network of ACC

Study Overview
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Brief Summary
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Hypothesis of AN-ACC pathological network suggests that ACC overactivation and abnormal functional connectivity with other brain regions is the neuropathological mechanism for the onset of AN. Currently, rare studies have been conducted on dTMS targeting ACC as an intervention in patients with AN. In this research, dTMS, a neuroregulatory technology, was used for the first time to intervene with ACC in the treatment of adult AN. A randomized controlled study design was adopted, in which patients with AN were divided into the dTMS treatment group and the pseudo-stimulation group by 1:1 randomization, followed by 6-week intervention and half-year follow up, to clarify the near-term and long-term efficacy and safety of the dTMS treatment. Meanwhile, baseline fMRI data were extracted and combined with clinical features to establish an efficacy prediction model, which will provide theoretical and practical basis for the pioneering ACC-targeted dTMS treatment in China, helping to establish a new type of intervention program for AN, with expected results of innovation.

Detailed Description
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Building on the previous foundation and literature review, we found that ACC is closely related to the core symptoms of AN, and proposed the hypothesis of AN-ACC pathological network, suggesting that ACC overactivation and abnormal functional connectivity with other brain regions (anterior frontal lobe, parietal lobe, precuneus, and striatum) is the neuropathological mechanism for the onset of AN. Currently, rare studies have been conducted on dTMS targeting ACC as an intervention in patients with AN. In this research, dTMS, a neuroregulatory technology, was used for the first time to intervene with ACC in the treatment of adult AN. A randomized controlled study design was adopted, in which patients with AN were divided into the dTMS treatment group and the pseudo-stimulation group by 1:1 randomization, followed by 6-week intervention and half-year follow up, to clarify the near-term and long-term efficacy and safety of the dTMS treatment. Psychometric and fMRI examinations are performed at baseline in both groups. The rest of the time follow-up of symptoms and psychometrics and side-effects questionnaires are performed at week 2, 4, and 6 (during treatment) as well as at week 4, 12, and 24 ( after completion of treatment). Meanwhile, baseline fMRI data were extracted and combined with clinical features to establish an efficacy prediction model. We will explore factors predictive of dTMS efficacy in AN patients of dTMS treatment group, divided into two groups according to whether dTMS was effective or not at the end of treatment (week 6) (effective is defined as BMI increasing by ≥1.2 kg/m2 at the end of treatment), using pre-treatment (baseline) demographic information, psychological assessment questionnaires, and neuroimaging data in the two groups. This will provide theoretical and practical basis for the pioneering ACC-targeted dTMS treatment in China, helping to establish a new type of intervention program for AN, with expected results of innovation.

Official Title
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A New Neuroregulatory Technology for the Therapy of AN Based on the Pathological Neural Network of ACC: A Multicenter Randomized Controlled Study

Conditions
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Feeding and Eating Disorders

Intervention / Treatment
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* Device: Deep transcranial magnetic stimulation
* Device: Sham deep transcranial magnetic stimulation
* Other: Basic treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female, aged 18-35 years, right handedness. Above primary education. Meet the diagnostic criteria of AN in DSM-V, and13.0 kg/m2 ≤ body mass index (BMI)<18.5 kg/m2. No systemic nutritional therapy, psychiatric medication or any form of psychotherapy have been received within 1 month before enrollment. Able to understand the nature of this study and sign an informed consent form. Exclusion Criteria: Diagnosed with a DSM-5 disease other than anorexia nervosa, or at high risk of suicide, strong impulsive behavior as well as anti-social behavior. With severe physical or cognitive impairment. Not able to undergo MRI. Considered unsuitable for enrollment in this clinical trial for other reasons.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dTMS treatment group<br>dTMS treatment group has 40 patients with dTMS intervention using real coils, targeting ACC, given 5 times a week for 6 weeks, with a total of 30 treatments. | Device: Deep transcranial magnetic stimulation<br>* Neuronavigation: The coil is positioned 4cm in front of the scalp point and foot motor cortex, corresponding to the ACC. The Brainways H7 coil with fluid cooling was used to obtain a greater depth of stimulation, up to about 6 cm below the cortex. dTMS intervention: the intervention targets were at the left and right ACC, 5 times per week (Monday through Friday), for 6 weeks, a total of 30 treatments were given. Stimulation mode: stimulation frequency 1Hz, stimulation intensity 100% RMT, number of pulses 150, sequence interval 20s, total 6 trials, 900 pulses.<br>Other: Basic treatment<br>* According to national and international guidelines for the treatment of eating disorders, the basic treatment for patients is nutritional therapy, that is, regular and quantitative dietary treatment, with three regular meals followed by a snack meal 2 hours after the regular meal. Both groups received the same nutritional treatment.<br>|
| Sham Comparator: pseudo-stimulation group<br>Pseudo-stimulation group has 40 patients with dTMS intervention using sham coils (with the same parameters as real dTMS and generating the same noise as real coils, but without the magnetic field). It is given 5 times a week for 6 weeks, with a total of 30 treatments. | Device: Sham deep transcranial magnetic stimulation<br>* Neuronavigation: The sham coil is positioned 4cm in front of the scalp point and foot motor cortex, corresponding to the ACC. Sham dTMS intervention: The intervention targets were at the left and right ACC (The sham coil has the same parameters as real dTMS and generating the same noise as real coils, but without the magnetic field), 5 times per week (Monday through Friday), for 6 weeks, a total of 30 treatments were given.<br>Other: Basic treatment<br>* According to national and international guidelines for the treatment of eating disorders, the basic treatment for patients is nutritional therapy, that is, regular and quantitative dietary treatment, with three regular meals followed by a snack meal 2 hours after the regular meal. Both groups received the same nutritional treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Mass Index (BMI). | Calculation: BMI = weight (kg) divided by the square of height (m) | Baseline, Week 2, 4, and 6 (during treatment) as well as Week 4, 12, and 24 ( after completion of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1.Eating Disorder Examination Questionnaire (EDE-Q6.0) | Eating Disorder Examination Questionnaire can assess the core symptoms of eating disorders, including behavioral and psychological characteristics, and rate their frequency and intensity, which can assess the severity of the eating disorder. It consists of 4 subscales, including dietary restriction, eating concerns, body image concerns, and weight concerns. | Baseline, Week 2, 4, and 6 (during treatment) as well as Week 4, 12, and 24 ( after completion of treatment) | 
| 2.Eating Disorder Inventory (EDI-II) | It is a commonly used scale for assessing cognitive-behavioral symptoms of eating disorders and is used to assess the severity of eating disorders. The scale contains 91 items divided into 8 subscales and 3 temporary subscales, including the pursuit of thinness, bulimia, body dissatisfaction, feelings of ineffectiveness, perfectionism, mistrust of others, introspection, maturity fears, abstinence, impulsive regulation and social insecurity. | Baseline, Week 2, 4, and 6 (during treatment) as well as Week 4, 12, and 24 ( after completion of treatment) | 
| 3.Beck Depression Inventory (BDI) | The BDI consists of 21 items and assesses the patient's accompanying feelings of depression over the past 2 weeks. | Baseline, Week 2, 4, and 6 (during treatment) as well as Week 4, 12, and 24 ( after completion of treatment) | 
| 4.Beck Anxiety Inventory (BAI) | The BAI consists of 21 items and assesses the patient's accompanying feelings of anxiety over the past 1 week. | Baseline, Week 2, 4, and 6 (during treatment) as well as Week 4, 12, and 24 ( after completion of treatment) | 
| 5. Self-assessed Compulsive Questionnaire for Eating Disorders (SR-YBC-EDS) | The SR-YBC-EDS was developed based on the Yale-Brown Compulsive Questionnaire for Eating Disorders (YBC-EDS), consisting of two parts: the first part is a list of 65 symptomatic items, which is used to identify the subjects' obsessive-compulsive symptoms, and the second part is a list of 8 core items, which is used to assess the frequency and severity of obsessive-compulsive symptoms. All parts contain two dimensions: preoccupation and ritual behavior. | Baseline, Week 2, 4, and 6 (during treatment) as well as Week 4, 12, and 24 ( after completion of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anorexia nervosa, Deep transcranial magnetic stimulation, anterior cingulate cortex