Deep Brain Stimulation for Severe Anorexia Nervosa

NCT ID: NCT05245643

Last Updated: 2024-07-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-14
• Study Completion Date: 2028-06-01

Brief Summary

The somatic complications as well as the suicidal risk make Anorexia Nervosa (AN) the psychiatric disease with the highest mortality rate: the standardized mortality ratio is higher than 4 and 1 in 5 patients with AN who dies has committed suicide. Approximately 20% of patients suffering from AN evolves into a chronic form without prolonged remission. These patients are at high risk of serious complications (somatic and psychiatric). The peak incidence of AN lies between 15 and 19 years: patients suffering from severe and resistant AN are therefore mostly young people. At present, there is no treatment for severe and resistant AN. New insights in AN pathophysiology revealed that AN patients develop a kind of "addiction" to thinness which contributes to weight loss despite negative consequences. In parallel, Deep Brain Simulation (DBS) is now widely performed for movements disorders with good results and low morbidity. DBS is also currently under investigations for other indications such as obsessional compulsive disorder or pharmacoresistant epilepsy. Some case series reported promising results of DBS for severe and resistant AN. The aim of this study is to investigate the safety of nucleus accumbens chronic stimulation for patients enduring severe and resistant AN. Secondary objective is to evaluate patient's acceptance of this new treatment.

Detailed Description

Main objective:

To selectively target for neuromodulation the key structures known to be involved in the motivational aspect of food intake, i.e. the nucleus accumbens, while evaluating safety and tolerance in the specific setting of AN patients (monitoring of serious adverse events [SAE])

Secondary objectives:

1. Evaluation of patient's acceptance,

2. Effect of DBS on weight stabilization (maintenance of patients' BMI above 14kg/m2),

3. Effect of DBS on pupillometry in patients with severe and resistant AN,

4. Effect of DBS on intermediate clinical variables such as loss of cognitive flexibility, overestimation of delayed rewards, and central coherence defect,

5. Effect of DBS on psychiatric comorbidities of patients suffering from severe and resistant AN.

Prospective multicenter study: interventional cohort

Practical conduct:

A. If all the inclusion criteria are met, proposal to participate in the study allowing a time window of 2 weeks of reflection before giving consent, B. Joint neurosurgeon/psychiatrist information consultation with delivery of a consent form, C. Preoperative assessment carried out after a delay of at least 2 weeks (anaesthesia consultation, brain MRI and neurocognitive assessment), D. Admisison in neurosurgery for one week to perform the DBS procedure. Post-operative CT Scan. The stimulation is turned on for all patients upon discharge from the hospital , E. Joint follow-up visit with the referring physician (once a month) and the neurosurgeon (once every 2 months) for 12 months F. Two neurocognitive assessments during follow-up visit : one early and one late postoperative (respectively at 5 and 11 months)

Inclusion period: 24 months Duration of preoperative assessment and reflection phase: 3 months Duration of participation (treatment + follow-up): 12 months Total duration: 40 months

Statistical analyses:

Descriptive results are presented as means ± standard deviations for continuous data and as percentages for categorical data.

The unpaired and paired t-test because of repeated measures in the same subjects, the Fisher's exact test will be use. A p<0.05 will be considered as statistically significant. A binomial sequence test is performed after each patient inclusion to check that the rate of SAE remains inferior to 25%.

Conditions

Anorexia Nervosa

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patients with severe and resistant Anorexia Nervosa

12 consecutive patients fulfilling the inclusion criteria and consenting to participate in the research, recruted in the three inclusion centers.

Group Type: OTHER

Abbott Infinity Deep Brain Stimulation System

Intervention Type: DEVICE

DBS is robot-assisted, with 3D intraoperative imaging control, under general anesthesia. Target is defined thanks to preoperative dedicated MRI with 2 independent experts' assessment.

Interventions

Abbott Infinity Deep Brain Stimulation System

DBS is robot-assisted, with 3D intraoperative imaging control, under general anesthesia. Target is defined thanks to preoperative dedicated MRI with 2 independent experts' assessment.

Intervention Type: DEVICE

Other Intervention Names

DBS of both nucleus accumbens

Eligibility Criteria

Inclusion Criteria

1. Diagnosis of Anorexia nervosa according to DSM V criteria.

2. Age 18 to 65 years.

3. Chronic, treatment-resistant anorexia nervosa, defined as:

• Anorexia nervosa evolving for at least 7 years.
• Inability to maintain a BMI ≥ 17kg/m² for 2 months following hospitalization in a center specialized for the management of patients suffering from eating disorders according to the criteria of the French Federation of Anorexia and Bulimia nervosa and the Directorate General of Care Provision (Direction Générale de l'Offre de Soins - DGOS, in French). Failure of at least 2 hospitalizations in a specialized center during the history of the disease.
• Inability to maintain a BMI ≥ 17kg/m² for more than 3 consecutive months during an outpatient treatment conducted by a team specialized for the care of patients suffering from eating disorders according to the criteria of the French Federation of Anorexia and Bulimia and the Directorate General of Care Provision (Direction Générale de l'Offre de Soins - DGOS, in French) in the year preceding the inclusion. Failure of at least 2 outpatient treatments conducted by a specialized team during the AN care.

4. Impaired psychological, social and occupational functioning defined by a score ≤ 45 on the Global Assessment of Functioning Scale.

5. Anorexia nervosa is judged to be the primary disorder if there are psychiatric comorbidities such as depression, anxiety disorder, obsessive-compulsive disorder, or personality disorder by at least two independent experts.

6. The patient is able to comply with the operational and administrative requirements of the study and is able to complete the protocol forms.

7. Patient provides written informed consent.

8. Patient is drug-free or on a medication that has been stable for at least 6 weeks at the time of study entry.

9. If female subject and of childbearing age: use of an effective method of contraception.

10. Membership in a health insurance plan or beneficiary.

Exclusion Criteria

1. Presence of an Axis I disorder that is primary to anorexia nervosa.

2. Presence of a personality disorder that could compromise compliance with post-surgical follow-up assessed by 2 independent experts

3. Presence of severe neurological pathology or significant MRI abnormalities (excluding anorexia-related atrophy).

4. Cognitive and intellectual ability to understand the risks and constraints of the technique or to give informed consent.

5. Albumin levels <30g/L.

6. Presence of medical contraindications to undergo implantation of a DBS system or to realize an MRI (pacemaker).

7. Pregnant or breastfeeding woman.

8. Previous DBS.

9. Trusted person and/or family object to patient's participation.

10. Contraindication to general anesthesia.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier St Anne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Viviane AWASSI

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Marc ZANELLO, MD, PhD

Role: CONTACT

m.zanello@ghu-paris.fr

+33 1 45 65 73 45

Facility Contacts

Marc ZANELLO, Dr

Role: primary

m.zanello@ghu-paris.fr

Viviane AWASSI

Role: backup

info-recherche@ghu-paris.fr

Other Identifiers

D21-P014

Identifier Type: -

Identifier Source: org_study_id