Clinical trial NCT06542900: Efficacy of Deep Brain Stimulation(DBS) for Treatment-Resistant Depression(TRD)
Official title: Effectiveness and Safety of Deep Brain Stimulation(DBS) in Treatment-Resistant Depression(TRD)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Treatment Resistant Depression
Keywords: TRD, DBS
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2024-08-07
Enrollment: 60
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
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to investigate the effect of deep brain stimulation (DBS) implantation in patients with Treatment-resistant Depression (TRD) targeting the ventral capsule/ventral striatum (VC/VS), Brodmann area 25/subcallosal cingulate (SCC), Anterior Limb of Internal Capsule (ALIC), inferior thalamic peduncle (ITP), nucleus accumbens (NAc), lateral habenula (LHb), medial forebrain bundle (MFB), or other unreported nuclei targets.

Detailed description: At least 40-60% of people with major depressive disorders (MDD) continue to have symptoms after treatment. The pharmacology treatment cannot produce sustained antidepressant effects in 50% of patients with depression. Therefore, more effective therapeutic methods are urgently needed. In a comprehensive survey of diverse neuromodulation therapies, targeting specific nuclei with deep brain stimulation (DBS) has the most potential for Treatment-resistant Depression (TRD) with apparent symptoms. The stimulation targets of DBS for patients with obsessive-compulsive disorder include the ventral capsule/ventral striatum (VC/VS), Brodmann area 25/subcallosal cingulate (SCC), Anterior Limb of Internal Capsule (ALIC), inferior thalamic peduncle (ITP), nucleus accumbens (NAc), lateral habenula (LHb), and medial forebrain bundle (MFB). However, the DBS case reports are limited and lack high-quality, evidence-based medical evidence. So, this cohort study focuses on the effectiveness of DBS-targeted VC/VS, SCC, ALIC, ITP, NAc, LHb, MFB, or other unreported nuclei targets on TRD.

Another goal of this program is to study the neuronal activity of the VC/VS, SCC, ALIC, ITP, NAc, LHb, MFB, or other unreported nuclei targets, respectively. At the same time, some subjects are presented with a task involving an unexpected reward. This separate study is an option and will not affect current study participation.

Some participants will also be invited to join a related study that involves positron emission tomography (PET) scanning to determine how the stimulation changes activity in the brain. Participation in the separate PET study is optional and will not affect current study participation.

Eligibility criteria: Inclusion Criteria:

1. male or female, 18-65 years old;
2. able to provide written informed consent voluntarily;
3. had a diagnosis of major depression disorder (MDD) (recurrent episodes) without psychotic features in compliance with the Diagnostic and Statistical Manual of Mental Disorders -Fourth Edition -Text Revised (DSM-IV-TR) and confirmed by the Mini-International Neuropsychiatric Interview Chinese version 5.0;
4. failure of response to at least two antidepressant medication trials based on the Massachusetts General Hospital antidepressant treatment response questionnaire (MGH-ATRQ);
5. ongoing antidepressant(s) at a fixed dose for at least four weeks before baseline assessment;
6. had a score of ≥201 on the Hamilton Depression Scale- item 17 (HAMD-17) at baseline.

Exclusion Criteria:

1. presence of other psychotic disorders;
2. have a treatment history that includes electroconvulsive therapy (ECT), modified electroconvulsive therapy (MECT), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), DBS, and transcranial magnetic stimulation (TMS);
3. presents a suicide risk (defined as a HAMD-17 score of ≥3 on suicide-related items);
4. experience difficulty in effectively communicating with investigators;
5. with a history of traumatic brain injury (TBI);
6. with intracranial or cardiovascular stents;
7. substance abuse within the past six months;
8. unstable neurological or coagulation disorders;
9. women who are pregnant, lactating, or of childbearing potential who refuse the use of reliable contraception during the study;
10. have been involved in other clinical studies within three months before enrollment in this study;
11. any conditions considered by the study group.

Primary outcomes:
measure: The change from baseline to 12 months in the Montgomery-Asberg Depression Rating Scale (MADRS) total score.
timeFrame: Baseline to 12 months post-surgery
Secondary outcomes:
measure: Remission, and response rate at week 2, month 3, month 6, and month 12, revealed by Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: the change from baseline to 2 weeks, 3 months, 6 months, and 12 months in the Hamilton Anxiety Rating Scale (HAMA) total score.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: the changes of Hamilton Depression Rating Scale, 17 item (HAMD-17) scores and its subscales from baseline to 2 weeks, 3 months, 6 months, and 12 months.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: the change of Pittsburgh Sleep Quality Index (PSQI) from baseline to Week 2, Month 3, Month 6, and Month 12.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: the change from baseline to 2 weeks, 3 months, 6 months, and 12 months in Clinical Global Impression-Severity scale (CGI-S)
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: the change of Clinical Global Impression-Improvement scale (CGI-I) at Week 2, Month 1, Month 3, Month 6, and Month 12.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: the change from baseline to Week 2, Month 3, Month 6, and Month 12 in EuroQol-5 Dimension-level Scale (EQ-5D-5L).
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: the change from baseline to Week 2, Month 1, Month 3, Month 6, and Month 12 in Young Mania Rating Scale (YMRS).
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: Safety as indicated by the number of Adverse Events at Week 2, Month 3, Month 6, and Month 12.
timeFrame: Baseline to week 2, month 3, month 6, and month 12
measure: the change from baseline to Month 12 in the Controlled Oral Word Association Test (COWAT).
timeFrame: 1 year after neurostimulator implantation.
measure: the change from baseline to Month 12 in the Trail-Making Test A&B
timeFrame: 1 year after neurostimulator implantation.
measure: the change from baseline to Month 12 in Rey-Osterrieth Complex Figure Test (ROCF).
timeFrame: 1 year after neurostimulator implantation.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Hongxing Wang, MD & PhD
role: PRINCIPAL_INVESTIGATOR
References: