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:
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.
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).