Remission Factors in Anorexia Nervosa

Study Overview
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Brief Summary
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Anorexia Nervosa (AN) is a complex and multifactorial psychiatric disease that affects mostly women and is characterized by a self-restriction of food intake leading to life-threatening consequences whose underlying mechanisms are largely unexplored. AN encompasses a constellation of risk factors including genetic, biological, neuro-psychological and social factors. Although AN has a prevalence of only 1-3% in the general population, it has the highest mortality rate amongst any psychiatric disorder. Recovery of normal feeding behaviour in patients often requires several months with a large between-patient variability and a high percentage of relapse, which can occur in 35 to 41% of the patients. There is a huge unmet need for optimal understanding of processes underlying relapse. Reward processing abnormalities represents an important hypothesis underlying AN development and perpetuation. We aim to investigate the mechanisms that contribute to the maintenance and chronicity of the disease after inpatient treatment with a longitudinal design across intensive standardized inpatient treatment. We will challenge our hypothesis through brain imaging, neuropsychological, metabolic and genetic approaches. One hundred twenty-five AN female patients admitted for intensive inpatient treatment will be recruited and evaluated: at admission, after weight recovery and at 6 months after discharge with neurocognitive tests (including the Delay Discounting Task), genetic/epigenetic examination, hormonal blood samples (at each visit and repeated sampling around a meal for a 10-patient subgroup) and brain imaging (including fMRI during a Delay Discounting Task for fifty patients). One hundred healthy controls will be also recruited and be subjected to the same study procedures.

Official Title
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Study of Remission Factors in Anorexia Nervosa of Adult Women (REMANO)

Conditions
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Anorexia Nervosa

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DMS 5 criteria for Anorexia Nervosa BMI < 18.5 kg/m² Being able to consent fluent in French Being affiliated to a social security scheme or being the beneficiary of such a scheme. Having signed the informed consent Exclusion Criteria: Deprived of liberty subject (judicial or administrative decision) Refusal to participate Presenting an unstabilized serious physical illness or psychiatric disorder compromising the follow up according investigator evaluation Contraindication for IRMf Pregnant or breast-feeding women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Anorexia Nervosa<br> | |
| Healthy Control Subjects<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delay Discounting Task score after weight recovery | Comparaison of this score to remission status six months post discharge | after complete weight recovery (4+/-2 months after inclusion) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delay Discounting Task score after weight recovery compared to control |  | after weight recovery (4+/-2 months after baseline) | 
| Bold signal difference during Delay Discounting Task in fMRI |  | Baseline (M0) and after weight recovery for patient (4+/-2 months after baseline) ; Baseline and 4 months later for healthy controls | 
| Evolution of brain volums in MRI |  | Baseline (M0), after weight recovery (4+/-2 months after baseline) | 
| Evolution of fronto striatal connectivity in MRI |  | Baseline (M0), after weight recovery (4+/-2 months after baseline) | 
| Evolution of total, acyl and desacyl ghrelin plasma level |  | Baseline (M0), after weight recovery (4+/-2 months after baseline) and 6 months post discharge | 
| Evolution of total, acyl and desacyl ghrelin plasma level around a meal |  | Baseline (Month 0), after weight recovery (4+/-2 months after baseline) during meal | 
| Exome analysis |  | Baseline (M0) | 
| Evolution of BDNF gene methylation |  | Baseline (M0), after weight recovery (4+/-2 months after baseline) | 
| Evolution of EDI-2 score | Evaluate the evolution of eating disorder dimensions during weight recovery predicting relapse | Baseline (M0), after weight recovery (4+/-2 months after baseline) and 6 months post discharge | 
| Evolution of EAI score | Evaluate the evolution of physical activity addiction during weight recovery predicting relapse | Baseline (M0), after weight recovery (4+/-2 months after baseline) and 6 months post discharge | 
| Evolution of GLT score | Evaluate the evolution of the level of physical activity during weight recovery predicting relapse | Baseline (M0), after weight recovery (4+/-2 months after baseline) and 6 months post discharge | 
| Evolution of YBS score | Evaluate the evolution of obession and compulsion during weight recovery predicting relapse | Baseline (M0), after weight recovery (4+/-2 months after baseline) and 6 months post discharge | 
| Evolution of HADS score | Evaluate the evolution of anxiety and depression during weight recovery predicting relapse | Baseline (M0), after weight recovery (4+/-2 months after baseline) and 6 months post discharge | 
| Evolution of Brixton score | Evaluate the evolution of neuropsychological performance during weight recovery predicting relapse | Baseline (M0), after weight recovery (4+/-2 months after baseline) and 6 months post discharge | 
| Evolution of TMT score | Evaluate the evolution of neuropsychological performance during weight recovery predicting relapse | Baseline (M0), after weight recovery (4+/-2 months after baseline) and 6 months post discharge | 
| Evolution of Slips of action neurocognitive score | Evaluate the evolution of neuropsychological performance during weight recovery predicting relapse | Baseline (M0), after weight recovery (4+/-2 months after baseline) and 6 months post discharge | 
| Evolution of pupillometry to social, food and body image pictures | Evaluate the evolution of neuropsychological performance during weight recovery predicting relapse | Baseline (M0), after weight recovery (4+/-2 months after baseline) and 6 months post discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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eating disorder, anorexia nervosa, delay discounting, ghrelin, genetic, epigenetic