Remotely Programmed Deep Brain Stimulation of the Bilateral Habenula for Treatment- Resistant Major Depression: An Open Label Pilot Trial

Study Overview
=================
Brief Summary
-----------------
The habenula(Hb) is an epithalamic structure located at the center of the dorsal diencephalic conduction system, a pathway involved in linking forebrain to midbrain regions. An increasing number of studies indicates that that overactivity in the lateral habeluna(LHb) is present during depressed states, where it could drive the changes in midbrain activity linked to depression. Deep brain stimulation(DBS) of the major afferent bundle (i.e., stria medullaris thalami) of the LHb can treat treatment-resistant major depression(TRD). There is no clinical case of directly stimulating habeluna for treatment TRD. This research will investigate effectiveness bilateral DBS to habenula for patients with TRD. Programming is a crucial aspect of DBS which directly influences its therapeutic efficacy. Researchers need to ascertain optimum stimulation parameters to help patients achieve optimal control of clinical symptoms. Remote programming of DBS can markedly improve patient convenience, minimize risk of infection and total treatment time and lead to an overall benefit for doctors and patients alike. This research will also investigate safety and benefit of remote programming of DBS.

Official Title
-----------------
Remotely Programmed Deep Brain Stimulation of the Bilateral Habenula for Treatment- Resistant Major Depression: An Open Label Pilot Trial

Conditions
-----------------
Treatment Resistant Major Depressive Disorder

Intervention / Treatment
-----------------
* Procedure: Bilateral surgical implantation of DBS system to Habeluna
* Other: Follow-up Period


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-65 years old Proficiency in Mandarin language; DSM-IV diagnosis of Majior depression disorder; Current episode duration ≥ 2 years; Failure to respond to a minimum of four different antidepressant treatments; Failure or intolerance of an adequate course of electroconvulsive therapy (ECT) during any episode; Capacity to provide informed consent (understanding of the study purpose and methods); Exclusion Criteria: Schizophrenia or history of psychosis unrelated to MDD; Antisocial personality disorder, dementia, current tic disorder; Past stereotactic neurosurgical intervention; Alcohol or substance abuse/dependence within 6 months; Neurological disease (Abnormal PET-CT, MRI, EEG); Contraindications of MRI-examination, e.g. implanted cardiac pacemaker/ heart defibrillator; Contraindications of stereotactic intervention, e.g. increased bleeding disposition, cerebrovascular diseases; Serious and unstable organic diseases (e.g. unstable coronal heart disease); HIV positive; Pregnancy and/or lactation;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: all subjects will receive bilateral surgical implantation of DBS system.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Deep Brain Stimulation<br>Device：Suzhou Sceneray® DBS system | Procedure: Bilateral surgical implantation of DBS system to Habeluna<br>* The SceneRay DBS device utilized in the present study is a double-channel device designed and manufactured by Suzhou Scene-Ray Medical Co., Ltd. The DBS system includes a dual-channel neurostimulator kit, lead kit, extension kit, clinician-operated wireless programmer, test stimulator, and patient controller. The lead (diameter =1.27 mm) contains four stimulating contacts made of platinumiridium alloy. The length of each contact is 1.5 mm, and interval spaces are 0.5 mm. This device shares the same basic principles utilized by Medtronic products, with unique wireless programming and electrode fixing designs. The amplitude (0-10 V), pulse width (60-960 ms), and frequency (1-1,600 Hz) can be programmed, and different frequencies may be utilized in the left and right hemispheres using this type of dual-channel IPG.<br>Other: Follow-up Period<br>* The researchers will remotely program the DBS biweekly after opening the stimulator and face to face test the patients' cognitive function every half year. Montgomery-Asberg Depression Rating Scale will be tested biweekly until the Programmed parameter has stable therapeutic efficacy and then tested after 3 months, 6 months, 9 months and 12 months.The other neuropsychological scales will be test on 3 months, 6 months, 9 months and 12 months.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Montgomery-Asberg Depression Rating Scale |  | Baseline (preoperative),Biweekly after onset of the DBS system,3 months,6 months, 9 months, 12 months | 
| Change in the Hamilton Depression Scale |  | Baseline（preoperative）,3 months, 6 months,9 months, 12months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Hamilton Anxiety Scale |  | Baseline（preoperative）,3 months, 6 months,9 months, 12months | 
| Change in the Quality of Life Assessment (SF-36) |  | Baseline（preoperative）,3 months, 6 months,9 months, 12 months | 
| Neuropsychological measures(Scores of cogstate battery) |  | Baseline（preoperative）,6 months,12 months | 
| Change in the Hamilton Anxiety Scale |  | Baseline（preoperative）,3 months, 6 months,9 months, 12 months | 
| Change in the WHO-BREF |  | Baseline（preoperative）,3 months,6 months,9 months, 12 months | 
| Change in Young Manic Rating Scale |  | Baseline (preoperative),Biweekly after onset of the DBS system,3 months,6 months, 9 months, 12 months | 
| Chang in Pittsburgh Sleep Quality Index |  | Baseline（preoperative）,3 months,6 months,9 months, 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bilateral Habeluna, Remote Deep Brain Stimulation, Treatment Resistant Major Depressive Disorder