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Deep Brain Stimulation for Patients With Chronic, Severe and Resistant Anorexia Nervosa

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ClinicalTrials.gov Identifier: NCT03168893
Recruitment Status : Recruiting
First Posted : May 30, 2017
Last Update Posted : May 30, 2017
Sponsor:
Information provided by (Responsible Party):
Víctor Pérez, Parc de Salut Mar

Tracking Information
First Submitted Date  ICMJE May 25, 2017
First Posted Date  ICMJE May 30, 2017
Last Update Posted Date May 30, 2017
Actual Study Start Date  ICMJE May 23, 2017
Estimated Primary Completion Date December 17, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 25, 2017)
Body mass index (BMI) [ Time Frame: From baseline till 12 months ]
BMI will be measured monthly from baseline till 12 months. Data will be compared with BMI in the beginning of the open label period
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 25, 2017)
  • Adverse events during the study [ Time Frame: From baseline till 12 months ]
  • Psychiatric comorbidity [ Time Frame: From baseline till 12 months ]
    Psychiatric comorbidity will be measured monthly from baseline till 12 months
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Deep Brain Stimulation for Patients With Chronic, Severe and Resistant Anorexia Nervosa
Official Title  ICMJE Deep Brain Stimulation on the Subgenual Cingulate and Accumbens Nucleus for Patients With Chronic, Severe and Resistant Anorexia Nervosa
Brief Summary Deep brain stimulacion (DBS) clinical study in the subcallosal cingulate (CSG) and accumbens nucleus (NAc) for 8 patients with treatment-refractory, cronic and severe anorexia nervosa (AN) patients. The main objective is to show efficacy and safety. Studies show that SSG and NAc are strategical targets in the pathophysiology and the hypothetical surgical treatment in AN patients. The patients distribution (4 patients in each target) it will made by the AN type and the comorbidity associated, the reasons are: 1- It is well known the comorbidity treatment imoportance in the AN evolution, 2- The two differentes types of AN have differents clinical behaviour and prognosis, 3- Studies show efficacy in TOC and DM patients with NAc DBS and in DM patients with CSG DBS. The main variable is BMI. After a 6 months stabilization evaluation phase will be followed (only in patients that have increase 10% BMI) by a double-bind, crossover phase, where patients will receive 3 months with stimulation turned on and 3 month with turned off. All patients will have a 12 months follow up. The study secondary objectives are to know the relation btween the stimulacion answer (increase 10% BMI) and the differents variables, specially AN type, associated cormobidity, selected target and preoperative MRI tractography study.
Detailed Description

HYPOTHESIS OF THE CLINICAL TRIAL

Based on the results of functional, preclinical, clinical and neurocircuit imaging studies in patients with Anorexia Nervosa (AN) and in the results of deep brain stimulation (DBS) in 81 other mental illnesses and in AN, our main hypotheses are:

  1. The subgeneric cingulate (CSG) and nucleus accumbens (NAc) are strategic targets in AN patients, so deep brain stimulation in these two targets may be effective in the treatment of AN patients.
  2. The stimulation of the CSG and the NAc has been safe in other mental illnesses so it can also be in patients with AN.

VARIABLES

The variables to be studied are: age, years of illness, number of admissions, type of AN, drugs tested, drugs at the present time, non-pharmacological treatments received, weight and current BMI, weight and mean BMI of the last year, associated comorbidity, Hamilton Scale for Depression (HAMD-17), Hamilton Scale for Anxiety (HAMA), Obsessive Compulsive Yale-Brown Scale (YBOCS), Cornell Scale for Eating Disorder (YBC-EDS), Quality of Life Scale SF-36, stimulation variables (voltage, frequency, pulse amplitude, active contacts), stimulated target (CSG, NAc), complications.

The main variable is the Body Mass Index (BMI). The baseline will be the mean BMI of the last 3 months pre-dating.

The variables will be collected preoperatively, after the surgery on a monthly basis until the end of the 12 months of follow-up from the surgery, and in the last month of follow-up of the study (month 33 of the study). Patient visits will be every 2 weeks from the start of the stimulation to 12 months of follow-up.

Response and referral criteria. Response to treatment is considered if BMI increases at least 10% of baseline BMI (baseline BMI: the mean of the last 3 months pre-engagement). Remission is considered if the BMI is greater than 18.5. The type of response in the associated comorbidities will be studied as a variable, but not as a criterion of response to treatment.

Concomitant treatments during the study: Patients will continue with the pharmacological treatment and with the previous psychotherapeutic therapies. During the study, modification of the drugs will not be allowed, but a dose adjustment if not an increase of more than 50%. All this must be recorded on the data collection sheet in the usual way. A new psychotherapeutic therapy can not be initiated during the study, and if it is done, the patient would leave the study.

Rescue measures against side effects of stimulation. The complication rate is very low (1-4%). In case of an infectious complication, the patient will receive antibiotic treatment. In case of a neurological complication (comitial crisis, feeling of discomfort), the generator can be turned off and restarted once the complication is resolved.

Rescue measures if clinical worsening in the off phase of double-blind. The generator will be connected, and the patient leaves the double-blind phase.

Rescue measures if worsening AN or some of their comorbidities (patient under stimulation). Pharmacological dose adjustment is permitted if it is not an increase of more than 50%, in case of having to be done, the patient would leave the study. It would not be possible to initiate a psychotherapy in which the patient was no longer present and, if required, the patient would leave the study.

Criteria for modifying the stimulation variables. There are two criteria that can modify the stimulation parameters: that there is no response to treatment (BMI), or that there is a side effect related to the stimulation (for example, a crisis in the hospital, discomfort). Changes in patient comorbidity will not be a criterion for modifying pacing parameters.

STAGES OF THE STUDY

Stage 1 (Documentation and recruitment). Its duration is 3-6 months. At this stage, all necessary documentation will be processed and the patients included in the study will be recruited, following the inclusion and exclusion criteria described below.

Stage 2 (Preoperative Evaluation, Surgical Intervention and Follow-up). This stage comprises month 4 to month 33 of the study. Once the patient was included in the study, with confirmation of the evaluation committee, and having received informed consent of the patient, the preoperative evaluation will be performed (Brain Resonance with tensor tractography, general analysis, chest x-ray, Electrocardiogram, psychometric tests, weight, body mass index, and neuropsychological evaluation). The period for the surgical procedure comprises month 4 to month 22 of the study, since all patients will be evaluated during a follow-up period of at least 12 months, and after a follow-up period, a period of evaluation of the results (3 months) is required. All surgeries and follow-up will be performed at the Hospital del Mar. In surgery, two cerebral electrodes (either in the Subgenual cingulate or in the Accumbens Nucleus) are connected to a subcutaneous generator at abdominal fat level, under general anesthesia, the hospitalization time is 3-4 days. The patient will initiate the stimulation of the stimulation system implanted prior to discharge. The patient will have control visits every 2 weeks (face-to-face or telephone) and monthly at the Hospital del Mar for the evaluation of scales, weight and possible side effects during the study's duration (minimum 1 year per patient). The patient will undergo an intraoperative cerebral CT scan and an immediate postoperative CT scan. Neuropsychological evaluation will be performed preoperatively and after 6 months of treatment. The follow-up stage of the patients in the study comprised month 4 of the study and month 33 of the study.

Stage 3 (Double Blind). This stage comprises a period of 6 months. After 6 months of stimulation, patients responding to stimulation (10% or greater increase in BMI compared to the mean BMI of the last 3 months of pre-engagement) will go on to a double-blind phase, in which 3 Months in on and 3 months in off, or vice versa (assigned by envelopes prior to the start of surgeries). Those patients who are in the off and worsen group (5% decrease in BMI from baseline) will be rescued by reestablishing the stimulation, and leaving the cross-study phase.In order to preserve masking, the CoiP (neurosurgeon, responsible for programming), will decide the changes in the stimulation remaining unrelated to the evaluation of the patients.

Stage 4 (Total collection of data and conclusions). This stage comprises from month 34 to month 36 of the study (last month of the project's 3 years).

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Anorexia Nervosa
Intervention  ICMJE
  • Device: Deep brain stimulation ON
    Infinity model of deep brain stimulation is placed ( 2 brain elecrodes and subcutaneus generator ) under general anhestesia. The system is activated
    Other Name: Deep Brain Stimulation: Infinity model device (ON)
  • Device: Deep brain stimulation OFF
    Infinity model of deep brain stimulation is placed ( 2 brain elecrodes and subcutaneus generator ) under general anhestesia. The system is not activated
    Other Name: Deep Brain Stimulation: Infinity model device (OFF)
Study Arms  ICMJE
  • Experimental: Deep brain stimulation ON
    Surgical procedure is necessary.In surgery, two cerebral electrodes (either in the Subgenual cingulate or in the Accumbens Nucleus) are connected to a subcutaneous generator at abdominal fat level, under general anesthesia. The patient will initiate the stimulation prior to discharge . At 6 months follow up, Deep brain stimulation continue 3 months more activated, patient and psychiatrist don´t know
    Intervention: Device: Deep brain stimulation ON
  • Experimental: Deep brain stimulation OFF
    Surgical procedure is necessary.In surgery, two cerebral electrodes (either in the Subgenual cingulate or in the Accumbens Nucleus) are connected to a subcutaneous generator at abdominal fat level, under general anesthesia. The patient will initiate the stimulation prior to discharge . At 6 months follow up, Deep brain stimulation is stopped during 3 months , patient and psychiatrist don´t know
    Intervention: Device: Deep brain stimulation OFF
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 25, 2017)
8
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 17, 2020
Estimated Primary Completion Date December 17, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

(All criteria for inclusion must be met)

  1. Age between 18-60 years
  2. Diagnosis of AN, both restrictive type and compulsion / purge type defined by the DSM-V-TR
  3. Chronicity: minimum of 10 years of illness.
  4. Resistance to treatment, shown by one or both of the following situations:

    A. That of the multiple treatments performed, at least 1 is an intensive treatment (hospitalization or day hospital), with one or more of the following results:

    • I have not been able to finish the treatment.
    • That it has finished but with little or no answer.
    • That in spite of having finished it, and of having answered, Has found a subsequent relapse in the first six months. B. Clinical situation of medical instability, accompanied by refusal to participate in any treatment program and including at least 1 episode of admission for involuntary feeding.
  5. Extremely serious (BMI less than 15), or severe (BMI between 15-15,99)
  6. Ability to sign informed consent
  7. Ability to undergo all tests and follow-ups of the study

Exclusion Criteria:

  1. BMI less than 13 at the time of recruitment for the study.
  2. Psychosis in the present moment or in the past.
  3. Current neurological disease.
  4. Substance or alcohol abuse and dependence in the last year.
  5. Contraindications to perform a brain MRI
  6. Presence of cardiac arrhythmias or other cardiac, respiratory, renal or endocrine affections, as a result of AN or not, that carries risk for the surgical procedure.
  7. Pregnancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gloria Villalba Martínez, Doctor 034 620305721 gloriavillalbamartinez@gmail.com
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03168893
Other Study ID Numbers  ICMJE ECP-AN-2016-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Víctor Pérez, Parc de Salut Mar
Study Sponsor  ICMJE Parc de Salut Mar
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gloria Villalba Martínez, Doctor Parc de Salut Mar
PRS Account Parc de Salut Mar
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP