Evaluation of CARdiac Abnormalities by Echocardiography and MRI in Malnourished Patients Suffering From Anorexia Nervosa (CARERA)

• ClinicalTrials.gov Identifier: NCT03600610
• Recruitment Status: Unknown
• First Posted: July 26, 2018
• Last Update Posted: July 26, 2018
• Sponsor: Assistance Publique Hopitaux De Marseille
• Information provided by (Responsible Party): Assistance Publique Hopitaux De Marseille

Study Description

Brief Summary:

Anorexia nervosa is an eating disorder occurring in adolescent females, characterized by voluntary dietary restriction, intense fear of gaining weight, and disturbed body image perception. Anorexia nervosa is characterized by the potential severity of its prognosis. While complete remission occurs in about 50% of cases, up to 20% of patients will develop a chronic relapsing form that leads to social disintegration. Moreover, anorexia nervosa has the highest mortality rate among psychiatric diseases with a risk of death of up to 10%. 30% of deaths in anorexia nervosa are attributed to cardiac complications remaining insufficiently described, and their screening at a preclinical stage is still poorly codified. Echocardiography findings show reduced left ventricular mass, pericardial effusion or mitral valve prolapse ; in addition, systolic function appears to be preserved whereas a global diastolic dysfunction, estimated with trans-mitral flow and global longitudinal strain. While the interest of cardiac echography has been well established, only one study used MRI as a means of cardiac evaluation in anorexia nervosa: interestingly, local myocardial fibrosis is pointed and could potentially contribute to cardiac rhythm disorders. No study has yet used T1-Mapping MRI to evaluate if diffuse myocardial fibrosis is prevalent in this population group.

The investigators conduct a transversal, observational, monocentric study whereby malnourished patients with anorexia nervosa and age- and sex- matched, normal weight, healthy volunteers will undergo a gadolinium-enhanced cardiac MRI. The primary objective of this study is to evaluate and compare the frequency of cardiac fibrosis in those populations. Other cardiac MRI parameters will be described and compared as secondary objectives. Moreover, non-cardiac parameters evaluated by MRI such as adipose tissue distribution in anorexia nervosa patients compared with controls.

In addition, patients with anorexia nervosa, a clinical, morphological and biological evaluation, including anthropometric parameters, biphotonic absorptiometry, resting electrocardiogram, cardiac echography and classical biological markers of malnutrition, will be done.

Condition or disease	Intervention/treatment	Phase
Anorexia Nervosa; Cardiac Anomaly	Device: gadolinium-enhanced cardiac MRI	Not Applicable

Detailed Description:

Anorexia nervosa is an eating disorder occurring most frequently in adolescent females, characterized by 1/ voluntary dietary restriction, leading to lower than normal body weight and, often, loss of considerable amount of weight and, thereby, malnutrition, 2/ intense fear of gaining weight, even when the individual is already underweight, starved or malnourished and 3/ disturbed body image perception, including extreme emphasis on the appearance. Anorexia nervosa is characterized by the potential severity of its prognosis. While complete remission occurs in about 50% of cases, up to 20% of patients will develop a chronic relapsing form that leads to social disintegration. Moreover, anorexia nervosa has the highest mortality rate among psychiatric diseases with a risk of death of up to 10% (including suicide and clinical complications of severe malnutrition). If approximatively 30% of deaths in anorexia nervosa are attributed to cardiac complications, the nature and the frequency of such complications remain insufficiently described, and their screening at a preclinical stage is still poorly codified. Echocardiography findings are well documented and include reduced left ventricular mass, pericardial effusion (in 22 to 35% of cases), or mitral valve prolapse (in up to 35% of cases); in addition, systolic function, evaluated by the ejection fraction appears to be preserved whereas a global diastolic dysfunction, estimated with trans-mitral flow and global longitudinal strain, is reported. While the interest of cardiac echography has been well established, only one study used MRI (magnetic resonance imaging) as a means of cardiac evaluation in anorexia nervosa: interestingly, this study found local myocardial fibrosis in nearly 25% of patients with anorexia nervosa, which could potentially contribute to cardiac rhythm disorders. That said, no study has yet used T1-Mapping MRI to evaluate if diffuse myocardial fibrosis is prevalent in this population group.

The investigators aim to conduct a transversal, observational, monocentric study whereby malnourished patients with anorexia nervosa (n = 38) and age- and sex- matched, normal weight, healthy volunteers (n = 38) will undergo a gadolinium-enhanced cardiac MRI. The primary objective of this study is to evaluate and compare the frequency of cardiac fibrosis in those populations using cardiac MRI. Other morphological and functional cardiac MRI parameters will be described and compared as secondary objectives: local myocardial fibrosis using enhanced MRI; myocardial and left ventricular mass; myocardial triglyceride quantification using Proton spectroscopy; cardiac high-energy metabolism using Phosphore-31 spectroscopy. Moreover, non-cardiac parameters evaluated by MRI such as adipose tissue distribution (visceral fat, liver fat, bone marrow fat) in anorexia nervosa patients compared with controls.

In addition, patients with anorexia nervosa, a clinical, morphological and biological evaluation, including anthropometric parameters, biphotonic absorptiometry, resting electrocardiogram, cardiac echography and classical biological markers of malnutrition, will be done. Multivariate analysis will then be used to identify possible correlating factors between cardiac MRI findings and clinical, morphological and biological parameters in malnourished patients with anorexia nervosa, so as to shed light on possible new risk stratification models or predictive tools for cardiac complications that could be later evaluated by appropriate studies.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 76 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Evaluation of CARdiac Morphological and Functional Abnormalities by Echocardiography and Magnetic Resonance Imaging in Malnourished Patients Suffering From Anorexia Nervosa
• Estimated Study Start Date: September 2018
• Estimated Primary Completion Date: September 2019
• Estimated Study Completion Date: March 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: patient group; malnourished patients with anorexia nervosa gadolinium-enhanced cardiac MRI will be performed	Device: gadolinium-enhanced cardiac MRI; cardiac magnetic resonance imaging with gadolinium injection used T1-Mapping
Active Comparator: control group; age- and sex- matched, normal weight, healthy volunteers gadolinium-enhanced cardiac MRI will be performed	Device: gadolinium-enhanced cardiac MRI; cardiac magnetic resonance imaging with gadolinium injection used T1-Mapping

Outcome Measures

Primary Outcome Measures :

1. Diffuse myocardial fibrosis [ Time Frame: 45 minutes ]
   Cardiac MRI (T1 Mapping shMOLLI) Diffuse myocardial fibrosis will be measured using ShMOLLI type T1 mapping methods to obtain high-resolution maps in the heart and a quantitative measure of fibrosis

Secondary Outcome Measures :

1. Local myocardial fibrosis [ Time Frame: 45 minutes ]
   Cardiac MRI (Late Gadolinium enhancement) Nodular myocardial fibrosis will be measured using late gadolinium enhancement after DOTAREM-gadolinium single dose injection (0.1 mmol / kg)
2. Myocardial triglycerides quantification [ Time Frame: 1hour ]
   quantification by Proton spectroscopy A T1 contrast sequence is used with a set of small-axis sections (n = 14) covering the entire heart for evaluation of pericardial adipose tissue volume
3. Cardiac metabolism [ Time Frame: 1day ]
   Phosphore-31 spectroscopy It will be evaluated by spectroscopy of phosphorus 31 (SRM-P31) with the study of phosphocreatine / adenosine triphosphate ratio

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Age > 18 years old
• Anorexia nervosa as defined by DSM-V with BMI < 15kg/m²
• Healthy controls with BMI within 18 to 25 kg/m²

Exclusion Criteria:

• History of cardiac disease previous to the diagnosis of anorexia nervosa
• On-going pregnancy or previous 3 month
• Breast feeding
• RMI contraindication
• History of allergic reaction to contrast product

Contacts and Locations

Contacts

Contact: patrice DARMON, MD; 04 91 38 36 53; patrice.darmon@ap-hm.fr

Locations

France

Assistance Pubique Des Hopitaux de Marseille

Marseille, Paca, France, 13354

Contact: PATRICE DARMON, MD 04 91 38 36 53 patrice.darmon@ap-hm.fr

Sponsors and Collaborators

Assistance Publique Hopitaux De Marseille

Investigators

• Study Director: EMILIE GARRIDO PRADALIE; APHM

More Information

• Responsible Party: Assistance Publique Hopitaux De Marseille
• ClinicalTrials.gov Identifier: NCT03600610
• Other Study ID Numbers: 2018-22
• First Posted: July 26, 2018
• Last Update Posted: July 26, 2018
• Last Verified: July 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Heart Defects, Congenital; Anorexia; Anorexia Nervosa; Congenital Abnormalities; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Mental Disorders; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases