Clinical trial NCT03254017: Remotely Programmed Deep Brain Stimulation of the Bilateral Habenula for Treatment- Resistant Major Depression: An Open Label Pilot Trial
Official title: Remotely Programmed Deep Brain Stimulation of the Bilateral Habenula for Treatment- Resistant Major Depression: An Open Label Pilot Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Treatment Resistant Major Depressive Disorder
Keywords: Bilateral Habeluna
Remote Deep Brain Stimulation
Treatment Resistant Major Depressive Disorder
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2017-08-18
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: all subjects will receive bilateral surgical implantation of DBS system.
Primary purpose: TREATMENT

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.


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;

Primary outcomes:
measure: Change in the Montgomery-Asberg Depression Rating Scale
timeFrame: Baseline (preoperative),Biweekly after onset of the DBS system,3 months,6 months, 9 months, 12 months
measure: Change in the Hamilton Depression Scale
timeFrame: Baseline（preoperative）,3 months, 6 months,9 months, 12months
Secondary outcomes:
measure: Change in the Hamilton Anxiety Scale
timeFrame: Baseline（preoperative）,3 months, 6 months,9 months, 12months
measure: Change in the Quality of Life Assessment (SF-36)
timeFrame: Baseline（preoperative）,3 months, 6 months,9 months, 12 months
measure: Neuropsychological measures(Scores of cogstate battery)
timeFrame: Baseline（preoperative）,6 months,12 months
measure: Change in the Hamilton Anxiety Scale
timeFrame: Baseline（preoperative）,3 months, 6 months,9 months, 12 months
measure: Change in the WHO-BREF
timeFrame: Baseline（preoperative）,3 months,6 months,9 months, 12 months
measure: Change in Young Manic Rating Scale
timeFrame: Baseline (preoperative),Biweekly after onset of the DBS system,3 months,6 months, 9 months, 12 months
measure: Chang in Pittsburgh Sleep Quality Index
timeFrame: Baseline（preoperative）,3 months,6 months,9 months, 12 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Ruijin Hospital Functional Neurosurgery
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Ruijin Hospital Functional Neurosurgery
state: Shanghai
Study officials:
References:
citation: Sartorius A, Kiening KL, Kirsch P, von Gall CC, Haberkorn U, Unterberg AW, Henn FA, Meyer-Lindenberg A. Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient. Biol Psychiatry. 2010 Jan 15;67(2):e9-e11. doi: 10.1016/j.biopsych.2009.08.027. No abstract available.
citation: Kiening K, Sartorius A. A new translational target for deep brain stimulation to treat depression. EMBO Mol Med. 2013 Aug;5(8):1151-3. doi: 10.1002/emmm.201302947. Epub 2013 Jul 4. No abstract available.
citation: Fakhoury M. The habenula in psychiatric disorders: More than three decades of translational investigation. Neurosci Biobehav Rev. 2017 Dec;83:721-735. doi: 10.1016/j.neubiorev.2017.02.010. Epub 2017 Feb 13.
citation: Proulx CD, Hikosaka O, Malinow R. Reward processing by the lateral habenula in normal and depressive behaviors. Nat Neurosci. 2014 Sep;17(9):1146-52. doi: 10.1038/nn.3779.
citation: Bergfeld IO, Mantione M, Hoogendoorn ML, Ruhe HG, Notten P, van Laarhoven J, Visser I, Figee M, de Kwaasteniet BP, Horst F, Schene AH, van den Munckhof P, Beute G, Schuurman R, Denys D. Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2016 May 1;73(5):456-64. doi: 10.1001/jamapsychiatry.2016.0152.
citation: Li D, Zhang C, Gault J, Wang W, Liu J, Shao M, Zhao Y, Zeljic K, Gao G, Sun B. Remotely Programmed Deep Brain Stimulation of the Bilateral Subthalamic Nucleus for the Treatment of Primary Parkinson Disease: A Randomized Controlled Trial Investigating the Safety and Efficacy of a Novel Deep Brain Stimulation System. Stereotact Funct Neurosurg. 2017;95(3):174-182. doi: 10.1159/000475765. Epub 2017 Jun 2.
citation: Zhang C, Li D, Zeljic K, Tan H, Ning Y, Sun B. A Remote and Wireless Deep Brain Stimulation Programming System. Neuromodulation. 2016 Jun;19(4):437-9. doi: 10.1111/ner.12448. No abstract available.