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Deep Brain Stimulation for Severe Anorexia Nervosa (STIMARS)

Primary Purpose

Anorexia Nervosa

Status

Recruiting

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Abbott Infinity Deep Brain Stimulation System

About this trial

This is an interventional treatment trial for Anorexia Nervosa focused on measuring Disease Resistance, Deep brain stimulation, Neuropsychological Tests, Patient Acceptance of Health Care

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis of Anorexia nervosa according to DSM V criteria.
Age 18 to 65 years.
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.
Impaired psychological, social and occupational functioning defined by a score ≤ 45 on the Global Assessment of Functioning Scale.
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.
The patient is able to comply with the operational and administrative requirements of the study and is able to complete the protocol forms.
Patient provides written informed consent.
Patient is drug-free or on a medication that has been stable for at least 6 weeks at the time of study entry.
If female subject and of childbearing age: use of an effective method of contraception.
Membership in a health insurance plan or beneficiary.

Exclusion Criteria:

Presence of an Axis I disorder that is primary to anorexia nervosa.
Presence of a personality disorder that could compromise compliance with post-surgical follow-up assessed by 2 independent experts
Presence of severe neurological pathology or significant MRI abnormalities (excluding anorexia-related atrophy).
Cognitive and intellectual ability to understand the risks and constraints of the technique or to give informed consent.
Albumin levels <30g/L.
Presence of medical contraindications to undergo implantation of a DBS system or to realize an MRI (pacemaker).
Pregnant or breastfeeding woman.
Previous DBS.
Trusted person and/or family object to patient's participation.
Contraindication to general anesthesia.

Sites / Locations

Viviane AWASSIRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Patients with severe and resistant Anorexia Nervosa

Arm Description

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

Outcomes

Primary Outcome Measures

Rate of serious adverse event

A serious adverse event is defined as any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires inpatient hospitalization or causes prolongation of existing hospitalization Results in persistent or significant disability/incapacity May have caused a congenital anomaly/birth defect Requires intervention to prevent permanent impairment or damage. In this study, SAE are permanently monitored. After each patient inclusion, SAE rate is calculated: it has to remain inferior to 25% of the included population.

Secondary Outcome Measures

Measure of protocol acceptability

Number of patients meeting inclusion criteria and accepting treatment / Number of patients meeting inclusion criteria and offered treatment

BMI Monitoring

Variation of BMI.

Pupillometry variation

Pupillometry according to GHU PARIS Sainte Anne Clinique des Maladies Mentales et de l'Encéphale protocol.

Scores of Eating Disorder Inventory-2

The EDI consists of 8 subscales measuring drive for thinness, bulimia, body dissatisfaction, ineffectiveness, perfectionism, interpersonal distrust, interoceptive awareness, and maturity fears.

Scores of Delayed Discounting Task

measure of temporal discounting, the tendency for people to prefer smaller, immediate monetary rewards over larger, delayed rewards

Scores of The Brixton Spatial Anticipation Test

Measures the ability to detect rules in sequences of stimuli.

Scores of the Trail Making Test

assess executive function

Scores of the slips-of-action task

measure habit tendencies, the likelihood of making erroneous responses for devalued outcome

Scores of the Wisconsin Card Sorting Test

measure the ability to display flexibility in the face of changing schedules of reinforcement

Scores of the Montreal Cognitive Assessment

screening assessment for detecting cognitive impairment

Scores of the Dubois' five words testing

Assess the verbal episodic memory

Scores of the Rey-Osterrieth Complex Figure Test (ROCFT)

measure of constructional praxis and visual recall

Scores of the Hospital Anxiety and Depression scale

detect states of depression and anxiety

Scores of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS)

Rate the severity of obsessive-compulsive disorder symptoms

Scores of the Scale for Suicide Ideation

Measures the current intensity of patients' specific attitudes, behaviors, and plans to commit suicide on the day of the interview.

Scores of the Short Form (36) Health Survey

measure of health status

Scores of the Global Assessment of Functioning

Rate subjectively the social, occupational, and psychological functioning of an individual

Scores of the Zarit Burden Interview

Assess caregiving burden in clinical and research settings

The Taylor Complex Figure Test (TCFT)

measure of constructional praxis and visual recall

Full Information

NCT ID

NCT05245643

First Posted

May 26, 2021

Last Updated

July 12, 2022

Sponsor

Centre Hospitalier St Anne

1. Study Identification

Unique Protocol Identification Number

NCT05245643

Brief Title

Deep Brain Stimulation for Severe Anorexia Nervosa

Acronym

STIMARS

Official Title

STIMulation cérébrale Profonde Chez Des Patients Souffrant d'Anorexie Mentale Résistante et Sévère

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 14, 2022 (Actual)

Primary Completion Date

April 14, 2024 (Anticipated)

Study Completion Date

November 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre Hospitalier St Anne

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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: Evaluation of patient's acceptance, Effect of DBS on weight stabilization (maintenance of patients' BMI above 14kg/m2), Effect of DBS on pupillometry in patients with severe and resistant AN, Effect of DBS on intermediate clinical variables such as loss of cognitive flexibility, overestimation of delayed rewards, and central coherence defect, 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%.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Anorexia Nervosa

Keywords

Disease Resistance, Deep brain stimulation, Neuropsychological Tests, Patient Acceptance of Health Care

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Model Description

Prospective multicenter study: interventional cohort for surgical treatment (deep brain stimulation) in severe and resistant Anorexia Nervosa

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Patients with severe and resistant Anorexia Nervosa

Arm Type

Other

Arm Description

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

Intervention Type

Device

Intervention Name(s)

Abbott Infinity Deep Brain Stimulation System

Other Intervention Name(s)

DBS of both nucleus accumbens

Intervention Description

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.

Primary Outcome Measure Information:

Title

Rate of serious adverse event

Description

Time Frame

Through study completion (2 years)

Secondary Outcome Measure Information:

Title

Measure of protocol acceptability

Description

Number of patients meeting inclusion criteria and accepting treatment / Number of patients meeting inclusion criteria and offered treatment

Time Frame

At the end of the inclusions (2 years after study start)

Title

BMI Monitoring

Description

Variation of BMI.

Time Frame

Through study completion (each month), during 2 years

Title

Pupillometry variation

Description

Pupillometry according to GHU PARIS Sainte Anne Clinique des Maladies Mentales et de l'Encéphale protocol.

Time Frame

Through study completion: during the preoperative (2 weeks before the surgery), early postoperative (1 month after the surgery), late postoperative (4 months after the surgery) and end of study (11 months after the surgery) neurocognitive assessments

Title

Scores of Eating Disorder Inventory-2

Description

The EDI consists of 8 subscales measuring drive for thinness, bulimia, body dissatisfaction, ineffectiveness, perfectionism, interpersonal distrust, interoceptive awareness, and maturity fears.

Time Frame

Title

Scores of Delayed Discounting Task

Description

measure of temporal discounting, the tendency for people to prefer smaller, immediate monetary rewards over larger, delayed rewards

Time Frame

Title

Scores of The Brixton Spatial Anticipation Test

Description

Measures the ability to detect rules in sequences of stimuli.

Time Frame

Title

Scores of the Trail Making Test

Description

assess executive function

Time Frame

Title

Scores of the slips-of-action task

Description

measure habit tendencies, the likelihood of making erroneous responses for devalued outcome

Time Frame

Title

Scores of the Wisconsin Card Sorting Test

Description

measure the ability to display flexibility in the face of changing schedules of reinforcement

Time Frame

Title

Scores of the Montreal Cognitive Assessment

Description

screening assessment for detecting cognitive impairment

Time Frame

Title

Scores of the Dubois' five words testing

Description

Assess the verbal episodic memory

Time Frame

Title

Scores of the Rey-Osterrieth Complex Figure Test (ROCFT)

Description

measure of constructional praxis and visual recall

Time Frame

Title

Scores of the Hospital Anxiety and Depression scale

Description

detect states of depression and anxiety

Time Frame

Title

Scores of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS)

Description

Rate the severity of obsessive-compulsive disorder symptoms

Time Frame

Title

Scores of the Scale for Suicide Ideation

Description

Measures the current intensity of patients' specific attitudes, behaviors, and plans to commit suicide on the day of the interview.

Time Frame

Title

Scores of the Short Form (36) Health Survey

Description

measure of health status

Time Frame

Title

Scores of the Global Assessment of Functioning

Description

Rate subjectively the social, occupational, and psychological functioning of an individual

Time Frame

Title

Scores of the Zarit Burden Interview

Description

Assess caregiving burden in clinical and research settings

Time Frame

Title

The Taylor Complex Figure Test (TCFT)

Description

measure of constructional praxis and visual recall

Time Frame

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis of Anorexia nervosa according to DSM V criteria. Age 18 to 65 years. 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. Impaired psychological, social and occupational functioning defined by a score ≤ 45 on the Global Assessment of Functioning Scale. 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. The patient is able to comply with the operational and administrative requirements of the study and is able to complete the protocol forms. Patient provides written informed consent. Patient is drug-free or on a medication that has been stable for at least 6 weeks at the time of study entry. If female subject and of childbearing age: use of an effective method of contraception. Membership in a health insurance plan or beneficiary. Exclusion Criteria: Presence of an Axis I disorder that is primary to anorexia nervosa. Presence of a personality disorder that could compromise compliance with post-surgical follow-up assessed by 2 independent experts Presence of severe neurological pathology or significant MRI abnormalities (excluding anorexia-related atrophy). Cognitive and intellectual ability to understand the risks and constraints of the technique or to give informed consent. Albumin levels <30g/L. Presence of medical contraindications to undergo implantation of a DBS system or to realize an MRI (pacemaker). Pregnant or breastfeeding woman. Previous DBS. Trusted person and/or family object to patient's participation. Contraindication to general anesthesia.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Marc ZANELLO, MD, PhD

Phone

+33 1 45 65 73 45

m.zanello@ghu-paris.fr

Facility Information:

Facility Name

Viviane AWASSI

City

Paris

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marc ZANELLO, Dr

m.zanello@ghu-paris.fr

First Name & Middle Initial & Last Name & Degree

Viviane AWASSI

info-recherche@ghu-paris.fr

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Deep Brain Stimulation for Severe Anorexia Nervosa

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