Psychological Interventions and Transcranial Direct Current Stimulation for the Treatment of Major Depressive Disorder
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 210
- 试验地点
- 3
- 主要终点
- Change in Hamilton Depression Rating Scale scores (17-item version) between "double active" and "ptES-only"
研究概览
简要总结
First-line treatments for major depressive disorder (MDD), antidepressants and psychotherapy, are associated with refractoriness and discontinuation due to side effects, and logistical burdens, respectively. In this scenario, transcranial electrical stimulation (tES) is nowadays considered effective and safe for MDD, albeit with a modest effect size, and also prone to logistical burdens when performed in external facilities. In this regard, clinical investigation involving portable tES (ptES), and the potentiation of ptES with remotely-delivered psychological interventions, have shown positive, but preliminary, results.
Here, the investigators present the design and rationale of a single-center, multi-arm, randomized, double-blind, sham-controlled clinical trial with digital features, using ptES (ptES) and internet-based behavioral therapy (iBT) for MDD (PSYLECT). This study will evaluate the efficacy, safety, tolerability and usability of (1) active ptES + active iBT ("double-active"), (2) active ptES + sham iBT ("ptES-only"), and (3) sham ptES + sham iBT ("double-sham"), in adults with MDD, with a Hamilton Depression Rating Scale - 17 item version (HDRS-17) score ≥ 17 at baseline, during 6 weeks. No antidepressant washouts will be performed during the trial.
Three co-primary hypotheses are presented: changes in HDRS-17 will be greater in (1) "double-active" compared to "ptES-only", (2) "double-active" compared to "double-sham", and (3) "ptES-only" compared to "double-sham".
The investigators aim to enroll 210 patients (70 per arm). The results of this trial should also offer new insights regarding the feasibility and scalability of combined ptES and iBT for MDD, in the area of digital mental health.
详细描述
Major depressive disorder (MDD) is a prevalent, debilitating and chronic mental disorder, characterized by frequent recurrences and resistance to first-line treatments: antidepressants and onsite cognitive-behavioral therapy (CBT) are associated with discontinuation due to side-effects, and logistical burdens, respectively.
Non-invasive brain stimulation techniques (NIBS), such as repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES) (of which the most widely studied format is transcranial direct current stimulation - tDCS), are considered safe and tolerable interventions for MDD. While rTMS is already approved by the FDA for MDD, it involves daily visits to external facilities and is costly.
tES, on the other hand, albeit having failed to prove non-inferiority to a conventional antidepressant (escitalopram 20mg/day) in a previous trial, is less expensive than rTMS, and portable. Therefore, tES could be suitable for home-use under remote supervision by trained clinical staff, especially as an add-on intervention for MDD. In this scenario, recent pilot trials have suggested a possible combined effect of tES with psychological interventions, based on a mechanism known as "functional targeting", that is, using two or more interventions to engage the same brain area of interest.
The PSYLECT study is a parallel, 3-arm, randomized, double-blind, sham-controlled, single-center clinical trial, with digital features, devised to assess the efficacy, tolerability, safety and usability of: (1) active portable tES (ptES) + active internet-based behavioral therapy (iBT) ("double active"), (2) active ptES + sham iBT ("ptES-only"), and (3) sham ptES + sham iBT ("double-sham"), for the treatment of MDD, in adults, during 6 weeks.
The investigators will enroll 210 adult patients (70 per arm) diagnosed with MDD per DSM-5 criteria, regardless of being in treatment with conventional antidepressants, to receive either: "double-active", "ptES-only" or "double-sham", during 6 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
The iBT intervention is performed concomitantly to the ptES session, and consists of an app-based interactive protocol (with a chatbot and online videos), synchronized via bluetooth, to the ptES device. For PSYLECT, the chatbot iBT protocol has been translated from English to Portuguese, and all iBT videos are either presented with Portuguese subtitles, or in the case of meditation videos (which allow participants to close their eyes), have been dubbed to Portuguese. Further details about active and sham iBT sessions are not described in this platform to avoid breaking the blinding of future participants enrolled in this study, with means of access to this platform. The complete details will be provided when the study results are published or upon reasonable request.
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of major depressive disorder (MDD) per DSM-5 criteria
- •Hamilton Rating Scale (17-item version)-HDRS score ≥ 17 at baseline
- •Years of education ≥ 8
- •Having access to a smartphone with internet access at home
- •Treatment refractoriness ≤ 3 antidepressants, at optimal doses and for appropriate duration
- •No contraindications for tDCS (i.e., metallic plates on the head, brain devices, cochlear implants, cardiac pacemakers)
- •No suicidal ideation with planning, or attempted suicide, in the 4 weeks prior to baseline
排除标准
- •Other psychiatric diagnoses (i.e., schizophrenia, schizoaffective disorder, bipolar disorder, obsessive compulsive disorder, attention-deficit and hyperactivity disorder, personality disorders, substance dependence and/or abuse disorders). Obs.: Anxiety disorders, as a comorbidity, will not be an exclusion criterium.
- •Suspected or confirmed pregnancy
- •Lactation
- •Severe clinical or neurological conditions, including Post-Acute Sequelae of COVID-19
- •Depressive symptoms better explained by other clinical conditions (i.e., hypothyroidism, anemia) or other psychiatric disorders.
- •Use of benzodiazepines > 10mg diazepam or diazepam-equivalent per day
结局指标
主要结局
Change in Hamilton Depression Rating Scale scores (17-item version) between "double active" and "ptES-only"
时间窗: Week 0 (baseline) and Week 6.
Clinician-administered depression assessment scale. Score range = 0 - 52 (higher scores mean worse outcome).
Change in Hamilton Depression Rating Scale scores (17-item version) between "double active" and "double-sham"
时间窗: Week 0 (baseline) and Week 6.
Clinician-administered depression assessment scale. Score range = 0 - 52 (higher scores mean worse outcome).
Change in Hamilton Depression Rating Scale scores (17-item version) between "ptES-only" and "double-sham"
时间窗: Week 0 (baseline) and Week 6.
Clinician-administered depression assessment scale. Score range = 0 - 52 (higher scores mean worse outcome).
次要结局
- Change in Clinical Global Impression Rating Scale (Severity of Illness) scores (CGI-S)(Weeks 0 and 6.)
- Change in Young Mania Rating Scale (YMRS) scores(Weeks 2, 3, 4 and 6.)
- Change in Positive and Negative Affect Schedule scores (PANAS)(Weeks 0, 3 and 6.)
- Change in Hamilton Depression Rating Scale scores (17-item version)(Weeks 0, 2, 3, 4 and 6.)
- Change in Hamilton Anxiety Rating Scale scores (HAM-A)(Weeks 0, 3 and 6.)
- Clinical Global Impression Rating Scale (Global Improvement) score (CGI-I)(Week 6.)
- Change in State-Trait Anxiety Inventory scores (STAI-T and STAI-S)(Weeks 0, 3 and 6.)
- Change in Montgomery-Asberg Depression Rating Scale scores (MADRS)(Weeks 0, 2, 3, 4 and 6.)
- Change in Beck Depression Inventory - II scores (BDI - II)(Weeks 0, 2, 3, 4 and 6.)
- Change in Device usability Likert scale scores(Weeks 1, 2, 3, 4, 5 and 6.)
- Change in tDCS Adverse Event Questionnaire scores(Weeks 1, 2, 3, 4, 5 and 6.)
研究者
Andre R Brunoni
Associate Professor of the Medical School of the University of Sao Paulo (FMUSP), Principal Investigator
University of Sao Paulo