Clinical trial NCT03347487: 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
Overall status: TERMINATED
Phase: NA
Conditions: Treatment Resistant Major Depression Disorder
Keywords: Bilateral Habenula
Treatment Resistant Major Depressive Disorder
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2017-11-20
Enrollment: 7
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 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.


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;

Primary outcomes:
measure: changes in the Hamilton Depression Scale(HAMD-17) score from baseline to 9 months
timeFrame: Baseline (preoperative),one month, 3 months, 6 months, 9 months
measure: changes in the Montgomery-Asberg Depression Rating Scale from baseline to 9 months
timeFrame: Baseline (preoperative),one month, 3 months, 6 months, 9 months
Secondary outcomes:
measure: changes in the brain activity
timeFrame: Baseline (preoperative),one month, 9 months
measure: Side Effects
timeFrame: Baseline (preoperative),one month, 3 months, 6 months, 9 months
measure: Young Mania Rating Scale (YMRS)
timeFrame: Baseline (preoperative),one month, 3 months, 6 months, 9 months
measure: Changes in Hamilton Anxiety Scales(HAMA)
timeFrame: Baseline (preoperative),one month, 3 months, 6 months, 9 months
measure: Global Assessment of Functioning Scale(GAF)
timeFrame: Baseline (preoperative),one month, 3 months, 6 months, 9 months
measure: Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline (preoperative),one month, 3 months, 6 months, 9 months
measure: Changes in Beck Depression Inventory
timeFrame: Baseline (preoperative),one month, 3 months, 6 months, 9 months
measure: Chang in Pittsburgh Sleep Quality Index
timeFrame: Baseline (preoperative),one month, 3 months, 6 months, 9 months
measure: World Health Organization Quality of Life-BREF(WHO-BREF)
timeFrame: Baseline (preoperative),one month, 3 months, 6 months, 9 months
measure: the MOS item short from health survey (SF-36)
timeFrame: Baseline (preoperative),one month, 3 months, 6 months, 9 months
measure: Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form
timeFrame: Baseline (preoperative),one month, 3 months, 6 months, 9 months
measure: Sheehan Disability Scale
timeFrame: Baseline (preoperative),one month, 3 months, 6 months, 9 months
measure: Changes in Neuropsychological measures(Scores of CANTAB tasks)
timeFrame: Baseline (preoperative),3 months, 9 months
Other outcomes:
Locations:
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: 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.
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: 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.
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: 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.