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

Treatment Resistant Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03254017
• Other study ID #: Habenula DBS
• Status: Terminated
• Phase: N/A
• Start date: July 24, 2017
• Est. completion date: August 30, 2019

Study information

• Verified date: November 2019
• Source: Ruijin Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: August 30, 2019
• Est. primary completion date: November 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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;

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Treatment Resistant Major Depressive Disorder

Intervention

Procedure:
• Bilateral surgical implantation of DBS system to Habeluna
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.

Other:
• Follow-up Period
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.

Locations

Country	Name	City	State
China	Shanghai Ruijin Hospital Functional Neurosurgery	Shanghai	Shanghai
China	Shanghai Ruijin Hospital Functional Neurosurgery	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

Bergfeld IO, Mantione M, Hoogendoorn ML, Ruhé 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. — View 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. Review. — View 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. — View 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. — View 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. Review. — View 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. — View 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. — View Citation

Outcome

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