The Efficiency of Transcranial Direct Current Stimulation in the Treatment of Anorexia Nervosa

Study Overview
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Brief Summary
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The main goal of the study (a 3-week, randomized, double-blind, and placebo-controlled study) is to determine the effect of Transcranial Direct Current Stimulation (tDCS) on the mental state and advances in nutritional rehabilitation in patients with AN. The primary hypothesis assumes that tDCS will reduce the symptoms of depression, improve cognition functions and it will have a positive effect on the reduction of restriction related to body weight and diet.

Detailed Description
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The aim of the study is to assess the effect of tDCS stimulation on psychological and biological factors in patient suffering for AN with particular attention to the safety of such additional therapy. Transcranial direct current stimulation (tDCS) is a non-invasive and currently considered safe method of neurostimulation. It is based on the use of direct current of very low intensity, up to 2000uA-2mA, and supplying it to the brain through electrodes placed on the scalp. In this way, the polarity of the cell membranes of neurons is induced, and this influences changes in the cortical excitation of the brain. Results confirming the efficacy of such a therapeutic approach would provide support for the introduction of brain stimulations as a valuable part of treatment in psychiatric wards but also as a part of home-based treatment. The protocol was developed by a multidisciplinary researcher team of a psychiatrist, psychologist, psychotherapist and nutritionists. Thanks to this, it is possible to evaluate the progress taking place in various fields. To the best of our knowledge, this will be the first intervention study assessing the efficacy of tDCS in AN taking into account not only psychological tests, but also biochemical markers (including levels of neurotrophins) or the electrical activity of the brain.

Official Title
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The Efficiency of Transcranial Direct Current Stimulation in the Treatment of Anorexia Nervosa - a Randomised, Double-blind Clinical Trial

Conditions
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Anorexia Nervosa

Intervention / Treatment
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* Device: tDCS
* Device: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written Informed Consent Form, Patients aged 13-25 years old, Meet the DSM-5 criteria for AN, Body mass index (BMI) ≤ 17,5 kg/m2, A willingness and motivation to follow the study protocol. Exclusion Criteria: Not giving Informed, Written Consent Diagnosis of neurological diseases, as epilepsy; Contraindications to tDCS, ie. pacemakers, metal parts around the head; Psychiatric comorbidities (except specific personality disorder) including mental retardation, organic brain dysfunction, or addiction (except nicotine and caffeine); Pregnancy or pregnancy planning; Changes in psychopharmacotherapy during hospitalization

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 25 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: tDCS group<br>The tDCS group will receive the active brain stimulation. | Device: tDCS<br>* Patients will be receiving twice a day tDCS (applied current at 2mA) stimulation, for 3 weeks on working days (30 sessions in total) and each stimulation will last 25 minutes. The anode will be located on the left, while the cathode- on the right dorsolateral prefrontal area of scalp. The commercially available Soterix 1x1 tDCS mini-CT LTE device (model 1601-LTE) will be used for stimulation.<br>|
| Sham Comparator: Placebo group<br>The placebo group will receive the sham brain stimulation. | Device: Placebo<br>* Patients will be receiving twice a day sham stimulation, for 3 weeks on working days (30 sessions in total) and each stimulation will last 25 minutes. The anode will be located on the left, while the cathode- on the right dorsolateral prefrontal area of scalp. The commercially available Soterix 1x1 tDCS mini-CT LTE device (model 1601-LTE) will be used for stimulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in severity of eating disorder symptoms 1 | The severity of symptoms will be assessed with Eating Attitudes Test (EAT-26) | The test will be performed three times: Before stimulation, baseline (V1), immediately after stimulation (V2) and two weeks after the intervention (V3) | 
| Change in severity of eating disorder symptoms 2 | The severity of symptoms will be assessed with Eating Disorder Examination Questionnaire (EDE-Q 6.0). | The test will be performed three times: Before stimulation, baseline (V1), immediately after stimulation (V2) and two weeks after the intervention (V3) | 
| Change in eating habits and opinions about food and nutrition | To evaluate changes in eating habits and opinions about food and nutrition the Questionnaire of Eating Behaviours (QEB) will be used. It is a qualitative questionnaire designed to study eating habits and opinions about food and nutrition. The first part of the questionnaire covers the frequency of consumption of selected products, the frequency of eating meals and their typical composition. In the second part of the questionnaire, there are 26 statements about food and nutrition, which enable the assessment of the level of nutritional knowledge of the respondents. | The test will be performed two times: Before stimulation, baseline (V1) and two weeks after intervention (V3) | 
| Change in food intake variety | Food Intake Variety will be assessed with The Variety Food Consumption Questionnaire. It is a qualitative food consumption frequency questionnaire. It is a simple tool to collect information on the consumption of (yes / no) 63 assortment groups of products. | The test will be performed three times: Before stimulation, baseline (V1), immediately after stimulation (V2) and two weeks after the intervention (V3) | 
| Change in assessment of stress levels | The severity of stress will be assessed with Perceived Stress Scale (PSS-10). This test consists 10 questions and is used to measure stress based on subjective feelings related to problems and personal events, behavior, coping with stress. | The test will be performed three times: Before stimulation, baseline (V1), immediately after stimulation (V2) and two weeks after the intervention (V3) | 
| Change in severity of depressive symptoms 1 | Severity of depressive symptoms will be assessed with Beck's Depression Inventory (BDI) | The tests will be performed twice: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in severity of depressive symptoms 2 | Severity of depressive symptoms will be assessed with Questionnaire for the Diagnosis of Depression in Children and Adolescents (CDI2). | The tests will be performed twice: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in meta-cognition | To assess metacognitive abilities Meta-Cognition Questionnaire (MCQ-A) will be used. Reliable and valid instrument for measuring meta-cognitive beliefs in adolescents (12-18 lat). The MCQ-A assesses the severity of dysfunctional meta-cognitive beliefs in adolescents (12-18) that affect their daily functioning. The first and second subscales measures positive and negative beliefs about worry, Subscale 3 measures cognitive confidence, Subscale 4 measures beliefs about superstition, punishment and responsibility. Finally, subscale 5 measures cognitive self-consciousness,. | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in attention and perceptiveness | To assess levels of attention Color connection test (CTT-1, CTT-2) and Test of attention and perceptiveness will be used. | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in intensity of intrusive thoughts | To assess intensity of intrusive thoughts CY-BOCS scale will be used | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in intensity of rumination | To assess intensity of rumination the Ruminance-Reflectivity Questionnaire will be used | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in visual memory | To assess visual memory test BENTON will be used. This test is used to test memory, visual perception and graphomotor skills. The examined person draws the presented patterns (10 pieces) from memory or redraws them, depending on the version and methods of the research carried out by the researcher. | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in body image self-esteem | To assess body image self-esteem Appearance Self-Rating Sheet (ASRS) will be used. Assessment of 25 dimensions related to your body - (different parts of your body). The patient receives a visualization of the body figure on the drawing and evaluates its individual elements. The test allows you to assess the importance of appearance for patients, the assessment of satisfaction with one's appearance and the satisfaction index. | The test will be performed three times: Before stimulation, baseline (V1), immediately after stimulation (V2) and two weeks after the intervention (V3) | 
| Change in cognitive abilities 1 | To assess cognitive abilities Matching Familiar Figures Test (MFF) | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in cognitive abilities 2 | To assess cognitive abilities Verbal Fluency Test will be used. | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in electrolyte levels | To evaluate electrolyte levels (mmol/l) in blood serum following tests will be performed: sodium, phosphorus, magnesium, calcium | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in morphotic elements 1 | To evaluate morphotic elements complete morphology with smear will be performed: RBC - Red Blood Cell (M/µl) | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in morphotic elements 2 | To evaluate morphotic elements complete morphology with smear will be performed: Hemoglobin (mmol/l) Mean Corpuscular Hemoglobin Concentration (mmol/l) | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in morphotic elements 3 | To evaluate morphotic elements complete morphology with smear will be performed: Hematocrit | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in morphotic elements 4 | To evaluate morphotic elements complete morphology with smear will be performed: Mean Corpuscular Volume (fl) | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in morphotic elements 5 | To evaluate morphotic elements complete morphology with smear will be performed: Mean Corpuscular Hemoglobin (pg) | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in morphotic elements 6 | To evaluate morphotic elements complete morphology with smear will be performed: Ferritin ( ng/ml) | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in morphotic elements 7 | To evaluate morphotic elements complete morphology with smear will be performed: White Blood Cell (K/µl) Lymphocytes (K/µl) | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in morphotic elements 8 | To evaluate morphotic elements complete morphology with smear will be performed: Monocytes (G/l) | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Metabolic changes 1 | To evaluate metabolic changes in blood serum Thyroid parameters will be examined: FT3 (pmol/l), FT4 (pmol/l) | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Metabolic changes 2 | To evaluate metabolic changes in blood serum the pituitary gland parameter will be examined: TSH (µIU/ml) | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Neurophysiologic changes 1 | To evaluate neurophysiologic changes EEG (theta and alpha wave power) test will be performed | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Neurophysiologic changes 2 | To evaluate neurophysiologic changes fNIRs test will be performed | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in neurotrophin levels | To evaluate neurotrophin levels in blood serum tests will be performed: BDNF (pg/ml), Neurotrphin 3 and 4 (pg/ml), NGF (pg/ml) | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Change in food intake regulators: | To evaluate food intake regulators in blood serum tests will be performed: leptin (pg/ml), visfatin (pg/ml) | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 
| Body composition changes 1 | To evaluate body composition changes BIA body composition analysis will be performed: Body weight (kg) | The test will be performed three times: Before stimulation, baseline (V1), immediately after stimulation (V2) and two weeks after the intervention (V3) | 
| Body composition changes 2 | To evaluate body composition changes BIA body composition analysis will be performed: Intracellular and extracellular water (l/%) | The test will be performed three times: Before stimulation, baseline (V1), immediately after stimulation (V2) and two weeks after the intervention (V3) | 
| Body composition changes 3 | To evaluate body composition changes BIA body composition analysis will be performed: Lean body mass (kg/%) | The test will be performed three times: Before stimulation, baseline (V1), immediately after stimulation (V2) and two weeks after the intervention (V3) | 
| Body composition changes 4 | To evaluate body composition changes BIA body composition analysis will be performed: Fat mass (kg/%) | The test will be performed three times: Before stimulation, baseline (V1), immediately after stimulation (V2) and two weeks after the intervention (V3) | 
| Changes in HPA axis biomarker | To evaluate HPA axis cortisol (nmol/l) in blood serum will be tested | The test will be performed two times: Before stimulation, baseline (V1) and immediately after stimulation (V2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anorexia Nervosa, Brain stimulation, Eating disorders, Left dorsolateral prefrontal cortex, Transcranial direct current stimulation