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

NCT03254017 | Terminated DMC

• 1 other identifier: Habenula DBS
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

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.

Conditions

Treatment Resistant Major Depressive Disorder

Keywords

Bilateral Habeluna; Remote Deep Brain Stimulation; Treatment Resistant Major Depressive Disorder

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• 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

Study Arms (1)

Experimental Deep Brain Stimulation

EXPERIMENTAL

Device：Suzhou Sceneray® DBS system

Procedure: Bilateral surgical implantation of DBS system to Habeluna; Other: Follow-up Period

Interventions

Bilateral surgical implantation of DBS system to Habeluna PROCEDURE

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.

Experimental Deep Brain Stimulation

Follow-up Period OTHER

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.

Experimental Deep Brain Stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);

You may not qualify if:

• 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;

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (2)

Shanghai Ruijin Hospital Functional Neurosurgery

Shanghai, Shanghai Municipality, 200025, China

Location

Shanghai Ruijin Hospital Functional Neurosurgery

Shanghai, Shanghai Municipality, China

Location

Related Publications (7)

• 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.

  PMID: 19846068 BACKGROUND

• 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.

  PMID: 23828711 BACKGROUND

• 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.

  PMID: 28223096 BACKGROUND

• 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.

  PMID: 25157511 BACKGROUND

• 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.

  PMID: 27049915 BACKGROUND

• 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.

  PMID: 28571034 BACKGROUND

• 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.

  PMID: 27321195 BACKGROUND

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Department of Functional Neurosurgery

Model Details: all subjects will receive bilateral surgical implantation of DBS system.

Study Record Dates

• First Submitted: August 16, 2017
• First Posted: August 18, 2017
• Study Start: July 24, 2017
• Primary Completion: November 30, 2018
• Study Completion: August 30, 2019
• Last Updated: November 29, 2019

Record last verified: 2019-11

Locations

CN (2)