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

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

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, is used for the first time to intervene with ACC in the treatment of adult AN. A randomized controlled study design is adopted, in which patients with AN are 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 will be 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.

Study Overview

• Status: Recruiting
• Conditions: Feeding and Eating Disorders
• Intervention / Treatment: Other: Basic treatment; Device: Deep transcranial magnetic stimulation; Device: Sham deep transcranial magnetic stimulation

Detailed Description

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, is used for the first time to intervene with ACC in the treatment of adult AN. A randomized controlled study design is adopted, in which patients with AN are divided into the dTMS treatment group and the pseudo-stimulation group by 1:1 randomization, followed by a 28-day intervention (once a day) and half-year follow up, to clarify the near-term and long-term efficacy and safety of the dTMS treatment. Patients in both groups undergo fMRI examinations, complete delay discounting task (DDT) and body image task before and after each treatment session. Efficacy is judged by a weight gain of 4 kg in the four weeks following the intervention. Symptoms, psychometrics and side effect questionnaires are followed up at baseline, day 28 (at the end of treatment), and weeks 4, 8, 12 and 24 ( after completion of treatment).

Meanwhile, baseline fMRI data will be 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 is effective or not after treatment (defined as a weight gain of 4 kg in the four weeks following the intervention), 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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jue Chen, PHD; Phone Number: +8618017311203; Email: chenjue2088@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Jue Chen
      • Contact: Jue Chen, Ph.D; Phone Number: +8618017311203; Email: chenjue2088@163.com
      • Contact: Yijun Li; Phone Number: 021-34773523; Email: kjksmhc@yeah.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dTMS treatment group; dTMS treatment group has 40 patients with dTMS intervention using real coils, targeting ACC, given once per day, for 28 days, with a total of 28 treatments.	Other: Basic treatment; 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.; Device: Deep transcranial magnetic stimulation; 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 is used to obtain a greater depth of stimulation, up to about 6 cm below the cortex. dTMS intervention: The intervention targets are at the left and right ACC, once per day, for 28 days. A total of 28 treatments are given. Stimulation mode: stimulation frequency 1Hz, stimulation intensity 100% RMT, number of pulses 150, sequence interval 20s, total 6 trials, 900 pulses.
Sham Comparator: pseudo-stimulation group; 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 once per day, for 28 days, with a total of 28 treatments.	Other: Basic treatment; 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.; Device: Sham deep transcranial magnetic stimulation; Neuronavigation: The sham coil is positioned 4 cm in front of the scalp point and foot motor cortex, corresponding to the ACC. Sham dTMS intervention: The intervention targets are 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), once per day, for 28 days. A total of 28 treatments are given.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Mass Index (BMI).	Calculation: BMI = weight (kg) divided by the square of height (m)	whin 4 weeks 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, day 28 (at the end of treatment), and weeks 4, 8, 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, day 28 (at the end of treatment), and weeks 4, 8, 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, day 28 (at the end of treatment), and weeks 4, 8, 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, day 28 (at the end of treatment), and weeks 4, 8, 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, day 28 (at the end of treatment), and weeks 4, 8, 12 and 24 ( after completion of treatment).
6. Body Image Tasks	Tasks that address excessive concerns about body shape/weight include the following two parts: Body size estimation: The screen will present the above 30 body size pictures sequentially, the subjects will view the body size pictures in 4000ms, and then evaluate the body size of the body pictures in 4000ms, with a score of 1 representing "very low body weight", 4 representing "very overweight", and 4 representing "very overweight". A score of 1 represents "very low weight" and a score of 4 represents "very overweight". Body compare task: The screen will present the above 30 body images in turn, the subjects will have 4000ms to view their own images (with randomized distortions), and then they will have 4000ms to compare their actual body shape with the body shape in the images and assess their emotional level. 1 point represents "very calm" and 4 for "very anxious".	baseline, day 28 (at the end of treatment), and weeks 4, 8, 12 and 24 (after completion of treatment).
7. Delay Discounting Task (DDT task)	The study uses a DDT task in a food choice scenario to assess inhibitory impulses. The task requires subjects to make a decision between choosing a small reward in the present or a large reward in the future. Inhibition to choose a small reward in the present implies a strong intertemporal decision-making ability. The task begins with an assessment of their hunger, willingness to eat, and emotional feelings at the moment. Then they are asked to rate 40 pictures of food on a scale of 0 to 10 on five dimensions: familiarity, craving, positive and negative emotions, emotional intensity, and eating control. Pictures of foods with craving scores >7 and eating control <5, as well as matched in familiarity and emotion for use in the ensuing delay discounting task. The choice is made by pressing a button: Patients choosing to get less food immediately are given fewer coupons after the delay. But those waiting for a period of time to get more food are given more coupons after the delay.	baseline, day 28 (at the end of treatment), and weeks 4, 8, 12 and 24 (after completion of treatment).

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: Shanghai University of Traditional Chinese Medicine; Shanghai Tongji Hospital, Tongji University School of Medicine; Huadong Hospital
• Investigators: Principal Investigator: Jue Chen, PHD, Shanghai Mental Health Center

Publications and helpful links

General Publications

• Carmi L, Tendler A, Bystritsky A, Hollander E, Blumberger DM, Daskalakis J, Ward H, Lapidus K, Goodman W, Casuto L, Feifel D, Barnea-Ygael N, Roth Y, Zangen A, Zohar J. Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial. Am J Psychiatry. 2019 Nov 1;176(11):931-938. doi: 10.1176/appi.ajp.2019.18101180. Epub 2019 May 21.
• Bersani FS, Minichino A, Enticott PG, Mazzarini L, Khan N, Antonacci G, Raccah RN, Salviati M, Delle Chiaie R, Bersani G, Fitzgerald PB, Biondi M. Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: a comprehensive review. Eur Psychiatry. 2013 Jan;28(1):30-9. doi: 10.1016/j.eurpsy.2012.02.006. Epub 2012 May 3.
• Kodama N, Moriguchi Y, Takeda A, Maeda M, Ando T, Kikuchi H, Gondo M, Adachi H, Komaki G. Neural correlates of body comparison and weight estimation in weight-recovered anorexia nervosa: a functional magnetic resonance imaging study. Biopsychosoc Med. 2018 Oct 31;12:15. doi: 10.1186/s13030-018-0134-z. eCollection 2018.
• King JA, Bernardoni F, Geisler D, Ritschel F, Doose A, Pauligk S, Pasztor K, Weidner K, Roessner V, Smolka MN, Ehrlich S. Intact value-based decision-making during intertemporal choice in women with remitted anorexia nervosa? An fMRI study. J Psychiatry Neurosci. 2020 Mar 1;45(2):108-116. doi: 10.1503/jpn.180252.
• Yuan S, Wu H, Wu Y, Xu H, Yu J, Zhong Y, Zhang N, Li J, Xu Q, Wang C. Neural Effects of Cognitive Behavioral Therapy in Psychiatric Disorders: A Systematic Review and Activation Likelihood Estimation Meta-Analysis. Front Psychol. 2022 May 3;13:853804. doi: 10.3389/fpsyg.2022.853804. eCollection 2022.
• Roth Y, Tendler A, Arikan MK, Vidrine R, Kent D, Muir O, MacMillan C, Casuto L, Grammer G, Sauve W, Tolin K, Harvey S, Borst M, Rifkin R, Sheth M, Cornejo B, Rodriguez R, Shakir S, Porter T, Kim D, Peterson B, Swofford J, Roe B, Sinclair R, Harmelech T, Zangen A. Real-world efficacy of deep TMS for obsessive-compulsive disorder: Post-marketing data collected from twenty-two clinical sites. J Psychiatr Res. 2021 May;137:667-672. doi: 10.1016/j.jpsychires.2020.11.009. Epub 2020 Nov 4.
• Carmi L, Alyagon U, Barnea-Ygael N, Zohar J, Dar R, Zangen A. Clinical and electrophysiological outcomes of deep TMS over the medial prefrontal and anterior cingulate cortices in OCD patients. Brain Stimul. 2018 Jan-Feb;11(1):158-165. doi: 10.1016/j.brs.2017.09.004. Epub 2017 Sep 6.
• Lipsman N, Lam E, Volpini M, Sutandar K, Twose R, Giacobbe P, Sodums DJ, Smith GS, Woodside DB, Lozano AM. Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of an open-label trial. Lancet Psychiatry. 2017 Apr;4(4):285-294. doi: 10.1016/S2215-0366(17)30076-7. Epub 2017 Feb 24.
• Karaszewska D, Cleintuar P, Oudijn M, Lok A, van Elburg A, Denys D, Mocking R. Efficacy and safety of deep brain stimulation for treatment-refractory anorexia nervosa: a systematic review and meta-analysis. Transl Psychiatry. 2022 Aug 15;12(1):333. doi: 10.1038/s41398-022-02102-w.

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: November 28, 2023
• First Posted (Actual): December 1, 2023

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: anorexia nervosa; Deep transcranial magnetic stimulation; anterior cingulate cortex
• Additional Relevant MeSH Terms: Mental Disorders; Feeding and Eating Disorders
• Other Study ID Numbers: SHDC12023122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study protocol and baseline characteristics of participants.
• IPD Sharing Time Frame: Researchers will share data when the study is completed in December 2026.
• IPD Sharing Access Criteria: dTMS; anorexia nervosa; anterior cingulate cortex
• 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