Clinical trial NCT06166082: Stanford Neuromodulation Therapy (SNT) for the Treatment-Resistant Depression
Official title: Stanford Neuromodulation Therapy (SNT) for the Treatment-Resistant Depression: A Study Multicenter, Randomized, Double-blind, Placebo Parallel Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Treatment Resistant Depression
Keywords: Treatment Resistant Depression
TRD
Lead sponsor: Changping Laboratory
Sponsor class: OTHER
Collaborators: name: Xianyue Hospital, Xiamen
name: Hebei Mental Health Center, Baoding
name: HuiLongGuan Hospital, Beijing
name: Wuhan Mental Health Center, Wuhan
name: Zhumadian Second People's Hospital, Zhumadian
First posted: 2023-12-12
Enrollment: 130
Sex: ALL
Minimum age (years): 22
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a multicenter, randomized, double-blind, and sham-controlled trial using the identical protocol as the SNT to replicate the antidepressant efficacy of SNT for TRD. Patients will be recruited and randomly assigned (1:1 ratio) to receive active or sham groups from 5 hospitals in China. The interventions will last for 5 days and both groups will be followed up for 8 weeks on the same time schedules. During the intervention and at least the first 4 weeks of post-treatment, participants will keep a stable antidepressant regimen. The individualized SNT target in the left dorsolateral prefrontal cortex (DLPFC) will be generated from 30 minutes of resting-state functional MRI collected at baseline.

Detailed description: Repetitive Transcranial Magnetic Training (rTMS) is a non-invasive neuromodulation that has been approved by the Food and Drug Administration (FDA) for treating patients with treatment-resistant depression(TRD). In 2022, the US FDA approved a high-dose intervention called Stanford Neuromodulation Therapy (SNT) to achieve rapid relief of patient symptoms in TRD. This therapy involves 10 1800 pulse Intermittent Theta Burst Stimulation (iTBS) interventions per day for consecutive 5 days on the dorsolateral prefrontal cortex (DLPFC), with 50 minutes inter-session intervals. At the end of the SNT intervention, the response rate reached 71.4% (13.3% in the sham group); At the 4th week follow-up after treatment, the response rate was 69.2% (7.1% in the sham group). This therapy has the advantage of quickly taking effect in the treatment of patients with TRD in a short period. However, there are also some limitations with this therapy, such as the need to undergo 10 high-dose interventions with 1800 pulses per day, which takes about 9 hours and may reduce patient compliance with the treatment. In addition, this study is a single-center small sample trial (14 cases with active and 15 cases with sham stimulation). The SNT therapy brings confidence to TRD patients, its efficacy and safety need to be verified in multicenter, randomized, double-blind, placebo-parallel controlled clinical trials.

Eligibility criteria: Inclusion Criteria:

* Meet the diagnostic criteria of DSM-5(Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) for depression disorder without psychotic symptoms, and currently experiencing a recurrence episode;
* Hamilton Depression Scale (HAMD-17) scores for 17 items ≥ 20 points, and the Montgomery Asberg Depression Rating Scale (MADRS) score is ≥ 20 points;
* hospitalized/outpatient patients aged ≥ 22 and ≤ 65 years old, male or female;
* The Maudsley Staging Method (MSM) assesses patients as at least moderate refractory (MSM score ≥ 7 points);
* Stable use of antidepressants for 4 weeks before randomization, with the type of antidepressant used being selective serotonin reuptake Selective serotonin reuptake inhibitors (SSRIs) or/and serotonin and norepinephrine reuptake Serotonin-norepinephrine reuptake inhibitors (SNRIs), the therapeutic dose is within the dosage range as the drug manual recommended;
* Understand the trial and sign the informed consent form.

Exclusion Criteria:

* Meets DSM-5 diagnostic criteria for other mental disorders, including schizophrenia spectrum disorders, bipolar and related disorders, and psychiatric disorders Developmental disorders, neurocognitive disorders, or depression caused by substances and/or drugs, or other medical problems;
* Individuals with pacemakers, cochlear implants, or other metal objects, as well as any electronic devices implanted in the body, and those with claustrophobia Contraindications for magnetic resonance imaging scans such as fear, and contraindications for rTMS treatment;
* History of epilepsy (presence of at least 2 uninduced seizures more than 24 hours apart, or diagnosis of the epileptic syndrome, or seizures within the past 12 months); Or currently received medications or other treatments that will lower the seizure threshold Syndromes, or seizures within the past 12 months;
* Received TMS treatment before participating in the trial;
* Individuals who have received ECT or phototherapy within three months;
* No response to ECT treatment (\>8 times);
* Previously received antidepressant treatment with implanted devices (such as DBS, VNS);
* Concomitant organic brain diseases (such as ischemic stroke, cerebral hemorrhage, brain tumors, etc.) and a history of severe brain injury;
* Complicated with serious heart, liver, kidney diseases, diabetes, and other serious physical diseases, which cause abnormal symptoms and signs of brain nerves, Or physical exhaustion;
* Women of childbearing age who are currently pregnant, breastfeeding, or planning or may become pregnant during the trial period;
* Substance abuse or dependence (including alcohol, drugs, and other psychoactive substances) in the past year;
* First-degree relatives suffer from bipolar disorder;
* High risk of suicide;
* Difficulty in communication to understand or follow instructions, and unable to cooperate with treatment and evaluation;
* Current in clinical trials of other drugs or physical therapies (DBS, ECT, rTMS);
* The researchers believe it is not suitable to participate.

Primary outcomes:
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Pretreatment (baseline), 28 days post-treatment
Secondary outcomes:
measure: Change in MADRS
timeFrame: Baseline, Day 5 (Immediate Post-treatment), 7 days Post-treatment, 14 days Post-treatment, 21 days Post-treatment, 56 days Post-treatment]
measure: Change in the Hamilton Rating Scale for Depression (HAMD-17)
timeFrame: Baseline, Day 5 (Immediate Post-treatment), 7 days Post-treatment, 14 days Post-treatment, 21 days Post-treatment, 28 days Post-treatment, 56 days Post-treatment]
measure: Change in the Hamilton Rating Scale for Depression (HAMD-6) Score
timeFrame: Baseline, Day 1, 2, 3, 4 in treatment, Day 5 (Immediate Post-treatment), 7 days Post-treatment, 14 days Post-treatment, 21 days Post-treatment, 28 days Post-treatment, 56 days Post-treatment]
measure: Change in Quick Inventory of Depressive Symptomatology Self-Report (QIDS_SR)
timeFrame: Baseline, Day 5 (Immediate Post-treatment), 7 days Post-treatment, 14 days Post-treatment, 21 days Post-treatment, 28 days Post-treatment, 56 days Post-treatment]
measure: Safety estimated using YMRS
timeFrame: Baseline, Day 5 (Immediate Post-treatment)
measure: cognitive change in Digit Symbol Substitution Test (DSST）
timeFrame: Baseline, Day 5(Immediate Post-treatment)
measure: cognitive change in continuous performance test (CPT）
timeFrame: Baseline, Day 5(Immediate Post-treatment)
measure: cognitive change in Trail-Making Test (TMT)
timeFrame: Baseline, Day 5(Immediate Post-treatment)
measure: cognitive change in Digit Span Test (DST)
timeFrame: Baseline, Day 5(Immediate Post-treatment)
Other outcomes:
Locations:
city: Baoding
country: China
facility: Hebei Mental Health Center
city: Beijing
country: China
facility: HuiLongGuan Hospital
city: Wuhan
country: China
facility: Wuhan Mental Health Center
city: Xiamen
country: China
facility: Xianyue Hospital
city: Zhumadian
country: China
facility: Zhumadian Second People's Hospital
Study officials:
affiliation: Changping Laboratory
name: Hesheng Liu, Ph.D.
role: STUDY_CHAIR
References: