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DBS of the Habenula for Treatment- Resistant Major Depression

Primary Purpose

Treatment Resistant Major Depression Disorder

Status
Terminated
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Deep brain stimuation system implantation
Sponsored by
Ruijin Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Treatment Resistant Major Depression Disorder focused on measuring Bilateral Habenula, Treatment Resistant Major Depressive Disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Men and women(non-pregnant) aged 18-65 years old;
  • DSM-5 diagnosis (assessed by Structured Clinical Interview for DSM-5) of a current major depressive episode(MDE), either nonpsychotic unipolar major depressive disorder (MDD) or bipolar disorder (BD);
  • Chronic illness with current MDE ≥ 24 months duration and/or recurrent illness with at least a total of 4 lifetime episodes (including current episode ≥ 12 months) and a minimum of 5 y since the onset of the first depressive episode;
  • For subjects with a bipolar disorder: the last manic or hypomanic episode must have been ≥ 24 months before study enrollment and patients must be maintained on a mood stabilizer (e.g. lithium or another mood stabilizer approved for bipolar disorder)
  • Treatment resistance defined as Failure of at least 3 adequate treatments from at least two distinctly different classes (SSRI, SNRI, NaSSA, TCA+, lithium-addition) for a period of 6-8 weeks. If diagnosed as bipolar, failure to respond to (or inability to tolerate) a minimum of three treatments approved for bipolar disorder, including lithium and at least one medication FDA-approved for bipolar depression (e.g., olanzapine/fluoxetine combination, quetiapine, lurasidone).
  • At least 1 session of ECT, for which the series of ECT was terminated either due to adverse effects or insufficient response (including at least 6 sessions of bilateral ECT). Or unable to recieve ECT.
  • Symptom Severity: HAMD-17 total ≥21;
  • Stable antidepressant medical regimen for the month preceding surgery;
  • Anticipates a stable psychotropic medication regimen in the next 12 months;
  • Able and willing to give written informed consent;
  • Modified mini-mental state examination (MMSE) score ≥ 27；

Exclusion Criteria:

  • Schizophrenia /history of psychosis unrelated to MDD;
  • Severe personality disorder (assessed by SCID-II);
  • Alcohol or substance abuse/dependence within 6 months, excluding nicotine dependence;
  • Current substantial suicidal risk as defined by a plan or clear immediate intent for self-harm, or had a serious suicide attempt within the last year;
  • Neurological disease (e.g., Parkinson's disease)
  • Any history of seizure disorder or hemorrhagic stroke;
  • Abnormal brain MRI ;
  • Previous sterosurgery;
  • Any medical contraindication to surgery;
  • Does not have adequate family/friend support as determined by psychological screening and/or interview;
  • Unable to maintain a stable psychotropic medication regimen in the next 12 months;
  • Pregnant or has plans to become pregnant in the next 12 months;

Sites / Locations

  • Shanghai Ruijin Hospital Functional Neurosurgery

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Deep Brain Stimulation of Bilateral Habenula

Arm Description

Outcomes

Primary Outcome Measures

changes in the Hamilton Depression Scale(HAMD-17) score from baseline to 9 months
The score of the scale ranges from 0 to 50.
changes in the Montgomery-Asberg Depression Rating Scale from baseline to 9 months
The score of the scale ranges from 0 to 60.

Secondary Outcome Measures

changes in the brain activity
Side Effects
Young Mania Rating Scale (YMRS)
YMRS is an eleven-item multiple choice diagnostic questionnaire which psychiatrists use to measure the severity of manic episodes. The score of the scale ranges from 0 to 60. Higher score means more severity of mania.
Changes in Hamilton Anxiety Scales(HAMA)
Clinician administered assessment.The score of the scale ranges from 0 to 56.
Global Assessment of Functioning Scale(GAF)
Clinician administered assessment.The score of the scale Scores range from 100 (extremely high functioning) to 1 (severely impaired).
Columbia Suicide Severity Rating Scale (C-SSRS)
Clinician administered assessment.The Screener contains 6 "yes" or "no" questions in which respondents are asked to indicate whether they have experienced several thoughts or feelings relating to suicide over the past month and behaviors over their lifetime and past 3 months. Each question addresses a different component of the respondent's suicide ideation severity and behavior.
Changes in Beck Depression Inventory
Self-rating scale. The score of the scale ranges from 0 to 63. Higher score means more severity of depression.
Chang in Pittsburgh Sleep Quality Index
The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality over a 1-month time interval. The measure consists of 19 individual items, creating 7 components that produce one global score ranging from 0 to 21. The high score means poor quality of sleep.
World Health Organization Quality of Life-BREF(WHO-BREF)
The World Health Organization Quality of Life - BREF (WHOQOL-BREF) is a self-report questionnaire which assesses 4 domains of quality of life (QOL): physical health, psychological health, social relationships, and environment. It contains 26 items which is a 5 points scale. The higher score means better quality of life.
the MOS item short from health survey (SF-36)
SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting and are now widely utilized by managed care organizations and by Medicare for routine monitoring and assessment of care outcomes in adult patients. The higher score means better quality of life.
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form
The scoring of the Q-LES-Q-SF involves summing only the first 14 items to yield a raw total score. The last two items are not included in the total score but are stand-alone items. The raw total score ranges from 14 to 70.
Sheehan Disability Scale
Self-rating scale. The SDS is a composite of three self-rated items designed to measure the extent to which three major domains in the patient's life are functionally impaired by psychiatric or medical symptoms. The SDS assesses functional impairment in three major life domains: work, social life/leisure activities, and family life/home responsibilities. The higher scores mean more severity of disability.
Changes in Neuropsychological measures(Scores of CANTAB tasks)
Neuropsychological measures contains six tasks which are Stop Signal Task, Spatial Working Memory, Paired Associated Learning, Stocking of Cambridge, Intra Extra dimensional Set Shifting, Reaction time Task

Full Information

First Posted
November 11, 2017
Last Updated
June 6, 2021
Sponsor
Ruijin Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03347487
Brief Title
DBS of the Habenula for Treatment- Resistant Major Depression
Official Title
Deep Brain Stimulation of the Bilateral Habenula for Treatment- Resistant Major Depression: An Open Label Pilot Trial
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Terminated
Why Stopped
7 patients were included in this study which aimed for 13 participants. Preliminary data were sufficient for developing further study.
Study Start Date
November 13, 2017 (Actual)
Primary Completion Date
May 30, 2021 (Actual)
Study Completion Date
May 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ruijin Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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 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 and safety of bilateral DBS to habenula for patients with TRD. This study will also use structural and functional MRI to explore the underlying mechanism of Hb's effects on TRD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment Resistant Major Depression Disorder
Keywords
Bilateral Habenula, Treatment Resistant Major Depressive Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
All subjects will receive bilateral surgical implantation of DBS system.
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Deep Brain Stimulation of Bilateral Habenula
Arm Type
Experimental
Intervention Type
Procedure
Intervention Name(s)
Deep brain stimuation system implantation
Other Intervention Name(s)
DBS, Activa RC System
Intervention Description
All subjects will receive bilateral surgical implantation of DBS system.The Medtronic DBS 3389 electrode is utilized in this study. The DBS system includes a dual-channel neurostimulator kit, lead kit, extension kit, clinician-operated wireless programmer, test stimulator, and patient controller.
Primary Outcome Measure Information:
Title
changes in the Hamilton Depression Scale(HAMD-17) score from baseline to 9 months
Description
The score of the scale ranges from 0 to 50.
Time Frame
Baseline (preoperative),one month, 3 months, 6 months, 9 months
Title
changes in the Montgomery-Asberg Depression Rating Scale from baseline to 9 months
Description
The score of the scale ranges from 0 to 60.
Time Frame
Baseline (preoperative),one month, 3 months, 6 months, 9 months
Secondary Outcome Measure Information:
Title
changes in the brain activity
Time Frame
Baseline (preoperative),one month, 9 months
Title
Side Effects
Time Frame
Baseline (preoperative),one month, 3 months, 6 months, 9 months
Title
Young Mania Rating Scale (YMRS)
Description
YMRS is an eleven-item multiple choice diagnostic questionnaire which psychiatrists use to measure the severity of manic episodes. The score of the scale ranges from 0 to 60. Higher score means more severity of mania.
Time Frame
Baseline (preoperative),one month, 3 months, 6 months, 9 months
Title
Changes in Hamilton Anxiety Scales(HAMA)
Description
Clinician administered assessment.The score of the scale ranges from 0 to 56.
Time Frame
Baseline (preoperative),one month, 3 months, 6 months, 9 months
Title
Global Assessment of Functioning Scale(GAF)
Description
Clinician administered assessment.The score of the scale Scores range from 100 (extremely high functioning) to 1 (severely impaired).
Time Frame
Baseline (preoperative),one month, 3 months, 6 months, 9 months
Title
Columbia Suicide Severity Rating Scale (C-SSRS)
Description
Clinician administered assessment.The Screener contains 6 "yes" or "no" questions in which respondents are asked to indicate whether they have experienced several thoughts or feelings relating to suicide over the past month and behaviors over their lifetime and past 3 months. Each question addresses a different component of the respondent's suicide ideation severity and behavior.
Time Frame
Baseline (preoperative),one month, 3 months, 6 months, 9 months
Title
Changes in Beck Depression Inventory
Description
Self-rating scale. The score of the scale ranges from 0 to 63. Higher score means more severity of depression.
Time Frame
Baseline (preoperative),one month, 3 months, 6 months, 9 months
Title
Chang in Pittsburgh Sleep Quality Index
Description
The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality over a 1-month time interval. The measure consists of 19 individual items, creating 7 components that produce one global score ranging from 0 to 21. The high score means poor quality of sleep.
Time Frame
Baseline (preoperative),one month, 3 months, 6 months, 9 months
Title
World Health Organization Quality of Life-BREF(WHO-BREF)
Description
The World Health Organization Quality of Life - BREF (WHOQOL-BREF) is a self-report questionnaire which assesses 4 domains of quality of life (QOL): physical health, psychological health, social relationships, and environment. It contains 26 items which is a 5 points scale. The higher score means better quality of life.
Time Frame
Baseline (preoperative),one month, 3 months, 6 months, 9 months
Title
the MOS item short from health survey (SF-36)
Description
SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting and are now widely utilized by managed care organizations and by Medicare for routine monitoring and assessment of care outcomes in adult patients. The higher score means better quality of life.
Time Frame
Baseline (preoperative),one month, 3 months, 6 months, 9 months
Title
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form
Description
The scoring of the Q-LES-Q-SF involves summing only the first 14 items to yield a raw total score. The last two items are not included in the total score but are stand-alone items. The raw total score ranges from 14 to 70.
Time Frame
Baseline (preoperative),one month, 3 months, 6 months, 9 months
Title
Sheehan Disability Scale
Description
Self-rating scale. The SDS is a composite of three self-rated items designed to measure the extent to which three major domains in the patient's life are functionally impaired by psychiatric or medical symptoms. The SDS assesses functional impairment in three major life domains: work, social life/leisure activities, and family life/home responsibilities. The higher scores mean more severity of disability.
Time Frame
Baseline (preoperative),one month, 3 months, 6 months, 9 months
Title
Changes in Neuropsychological measures(Scores of CANTAB tasks)
Description
Neuropsychological measures contains six tasks which are Stop Signal Task, Spatial Working Memory, Paired Associated Learning, Stocking of Cambridge, Intra Extra dimensional Set Shifting, Reaction time Task
Time Frame
Baseline (preoperative),3 months, 9 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women(non-pregnant) aged 18-65 years old; DSM-5 diagnosis (assessed by Structured Clinical Interview for DSM-5) of a current major depressive episode(MDE), either nonpsychotic unipolar major depressive disorder (MDD) or bipolar disorder (BD); Chronic illness with current MDE ≥ 24 months duration and/or recurrent illness with at least a total of 4 lifetime episodes (including current episode ≥ 12 months) and a minimum of 5 y since the onset of the first depressive episode; For subjects with a bipolar disorder: the last manic or hypomanic episode must have been ≥ 24 months before study enrollment and patients must be maintained on a mood stabilizer (e.g. lithium or another mood stabilizer approved for bipolar disorder) Treatment resistance defined as Failure of at least 3 adequate treatments from at least two distinctly different classes (SSRI, SNRI, NaSSA, TCA+, lithium-addition) for a period of 6-8 weeks. If diagnosed as bipolar, failure to respond to (or inability to tolerate) a minimum of three treatments approved for bipolar disorder, including lithium and at least one medication FDA-approved for bipolar depression (e.g., olanzapine/fluoxetine combination, quetiapine, lurasidone). At least 1 session of ECT, for which the series of ECT was terminated either due to adverse effects or insufficient response (including at least 6 sessions of bilateral ECT). Or unable to recieve ECT. Symptom Severity: HAMD-17 total ≥21; Stable antidepressant medical regimen for the month preceding surgery; Anticipates a stable psychotropic medication regimen in the next 12 months; Able and willing to give written informed consent; Modified mini-mental state examination (MMSE) score ≥ 27； Exclusion Criteria: Schizophrenia /history of psychosis unrelated to MDD; Severe personality disorder (assessed by SCID-II); Alcohol or substance abuse/dependence within 6 months, excluding nicotine dependence; Current substantial suicidal risk as defined by a plan or clear immediate intent for self-harm, or had a serious suicide attempt within the last year; Neurological disease (e.g., Parkinson's disease) Any history of seizure disorder or hemorrhagic stroke; Abnormal brain MRI ; Previous sterosurgery; Any medical contraindication to surgery; Does not have adequate family/friend support as determined by psychological screening and/or interview; Unable to maintain a stable psychotropic medication regimen in the next 12 months; Pregnant or has plans to become pregnant in the next 12 months;
Facility Information:
Facility Name
Shanghai Ruijin Hospital Functional Neurosurgery
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
19846068
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.
Results Reference
background
PubMed Identifier
17498883
Citation
Sartorius A, Henn FA. Deep brain stimulation of the lateral habenula in treatment resistant major depression. Med Hypotheses. 2007;69(6):1305-8. doi: 10.1016/j.mehy.2007.03.021. Epub 2007 May 10.
Results Reference
background
PubMed Identifier
23828711
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.
Results Reference
background
PubMed Identifier
25726497
Citation
Dougherty DD, Rezai AR, Carpenter LL, Howland RH, Bhati MT, O'Reardon JP, Eskandar EN, Baltuch GH, Machado AD, Kondziolka D, Cusin C, Evans KC, Price LH, Jacobs K, Pandya M, Denko T, Tyrka AR, Brelje T, Deckersbach T, Kubu C, Malone DA Jr. A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression. Biol Psychiatry. 2015 Aug 15;78(4):240-8. doi: 10.1016/j.biopsych.2014.11.023. Epub 2014 Dec 13.
Results Reference
background
PubMed Identifier
27049915
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.
Results Reference
background
PubMed Identifier
34251338
Citation
Huang Y, Sun B, Debarros J, Zhang C, Zhan S, Li D, Zhang C, Wang T, Huang P, Lai Y, Brown P, Cao C, Tan H. Increased theta/alpha synchrony in the habenula-prefrontal network with negative emotional stimuli in human patients. Elife. 2021 Jul 12;10:e65444. doi: 10.7554/eLife.65444.
Results Reference
derived

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DBS of the Habenula for Treatment- Resistant Major Depression

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