Efficacy of Bright Light Therapy on Cognitive Impairment in Major Depressive Disorder and Its Neuroimaging Mechanisms: Protocol for a Randomised Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Symbol Coding (SC)
研究概览
简要总结
This study aims to validate the therapeutic efficacy and safety of bright light therapy (BLT) in ameliorating cognitive impairment (CI) in major depressive disorder (MDD), characterize the functional and structural features of the hippocampus (HPC)-dorsolateral prefrontal cortex (dlPFC) neural circuitry in MDD participants with CI and examine the mediating effect of the HPC-dlPFC neural circuit on CI induced by BLT treatment in MDD participants. MDD participants will be required to only receive selective serotonin reuptake inhibitors (SSRIs) as monotherapy for at least four weeks, or medication-free status before enrollment. Eligible participants will be randomly assigned to the experimental group and the control group. The experimental group will receive the intervention of BLT, and the control group will receive the intervention of dim red light (DRL). The intervention will last for four weeks, 6 days per week, with 40 minutes each day between 7 am and 10 am. The MDD participants will be followed once in the end of each week during the 4-week intervention and in the end of the 4th week after intervention. Demographic information will be collected at baseline; cognitive function will be evaluated at baseline, weeks 2, 4, and 8 after intervention beginning; and other symptoms such as depression, anxiety and sleep were assessed at baseline, weeks 1, 2, 3, 4, and 8 after intervention beginning. Moreover, structural and functional MRI scans will be made at baseline and post-intervention. During the intervention, MDD participants will be required to keep a record of daily light exposure duration and complete the daily sleep diary as well.
详细描述
This study is mainly designed as a randomized controlled study. It focuses on CI in MDD participants, with an experimental group and a control group established. MDD participants will be required to only receive selective serotonin reuptake inhibitors (SSRIs) as monotherapy for at least four weeks, or medication-free status before enrollment. The medication dosage need to maintain unchanged throughout the entire intervention. The experimental group received the intervention of BLT, and the control group additionally received the intervention of dim red light (DRL). The intervention lasts for four weeks (six days per week, with 40 min per day between 7am and 10 am). Follow-up will be conducted once at the 4th weekends after intervention. Cognitive appraisal will be conducted using a composite battery derived from the Chinese version of Measurement Consensus Cognitive Battery (MCCB), the Chinese Biref Cognitive Test(C-BCT), and Perceived Deficits Questionnaire(PDQ)at baseline, weeks 2, 4 and 8 after intervention beginning. Other clinical symptoms will be assessed by The 17-item Hamilton Depression Rating Scale (HAMD-17), the 16-item Quick Self Rating Depression Symptoms Scale (QIDS), Hamilton Anxiety Rating Scale (HAMA), the 7-item Generalized Anxiety Disorder Scale (GAD-7), Pittsburgh sleep quality index (PSQI), Insomnia Severity Index (ISI), Chinese version of the Short Form of Quality of Life Enjoyment and Satisfaction Questionnaire(Q-LES-Q-SF) and Sheehan Disability Scale(SDS) at baseline, weeks 1, 2, 3, 4 and 8 after intervention beginning. At the same time, the Safety and Applicability of the intervention during the treatment process will be investigated using Young Mania Rating Scale (YMRS), the Side Effects Rating Scale for Serotonin Specific Reuptake Inhibitors (SERS) and a self-made scale.
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
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •The inclusion and
排除标准
- •for MDD patients. 1、Inclusion Criteria:
- •MDD diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-Ⅳ), first episode or recurrence, confirmed by an experienced psychiatrist using the Mini International Neuropsychiatric Interview.
- •Age between 18 and 60 years; and gender no-limited;
- •The severity of MDD symptoms must be ≥14 scores on the HAMD-17;
- •With CI currently, defined as a total score of <70 on the SC;
- •A SSRI monotherapy at stable dosages for at least 4 weeks; or medication-free status;
- •Education level above primary school, able to understand and cooperate in completing the study procedures;
- •Voluntarily participating in this study and sign the informed consent before enrollment.
- •2、Exclusion Criteria:
- •Current or past diagnosis of any disorder other than MDD according to DSM-Ⅳ criteria;
- •The scores on the Young Mania Rating Scale (YMRS) are>8;
- •The participants who have undergone other intervention in addition to SSRIs whinin the past 6 months or now, or who plan to do that in 1 month;
- •The participants with strong self-blame, self-harm, or suicidal risks (the HAMD-17 suicide item score of ≥3);
- •The participants with severe physical illnesses, including heart failure, renal failure, severe liver dysfunction, hyperthyroidism, or hypothyroidism; Or a history of severe brain trauma or organic brain pathology (e.g., intracerebral hemorrhage, large-area cerebral infarction, encephalitis, epilepsy), as well as neurological diseases;
- •The participants with any degree of retinal pathology, including retinal dystrophy, age-related macular degeneration, diabetic retinopathy, cataracts, glaucoma, or other ocular diseases;
- •The participants with photosensitive conditions, such as systemic lupus erythematosus, porphyria, chronic photodermatitis, solar urticaria, or those currently receiving medications that may increase photosensitivity (e.g., phenothiazines, antimalarials, propranolol, hypericin, stimulants, or chronic treatment with nonsteroidal anti-inflammatory drugs);
- •Pregnant or lactating women;
- •The participants with contraindications to MRI, such as the presence of non-MRI-safe metallic implants or claustrophobia;
- •The participants deem unsuitable for inclusion in this study by the investigator for other reasons.
- •Withdrawal and Termination Criteria：
- •The participants meet one of the exclusion criteria above after enrollment;
- •When the participants' treatment regimen need change;
- •The participants who fail to cooperate or voluntarily withdraw from the study;
- •Due to severe adverse events, the patients are unable to tolerate phototherapy;
- •The participants who fail to adhere to the study protocol intervention for three consecutive days or for a cumulative duration exceeding seven days;
- •Cancellation of the study.
- •The inclusion and exclusion criteria for Health controls
- •1. Inclusion criteria
- •Age between 18 and 60 years; and gender no-limited;
- •Without CI currently, defined as a total score of ≤ 70 on the SC;
- •Education level above primary school, able to understand and cooperate in completing the study procedures;
- •Voluntarily participating in this study and sign the informed consent before enrollment.
- •2.Exclusion criteria
- •Current or past diagnosis of any psychiatric disorders, or history of substance/drug abuse or dependence;
- •Current or past diagnosis of severe somatic diseases, such as heart failure, renal failure, severe liver dysfunction, or hyperthyroidism/hypothyroidism;
- •History of severe traumatic brain injury or organic brain lesions;
- •Pregnant or lactating women;
- •The participants with contraindications to MRI, such as the presence of non-MRI-safe metallic implants or claustrophobia.
- •The participants deem unsuitable for inclusion in this study by the investigator for other reasons.
研究组 & 干预措施
healthy control
DRL control group
Eligible MDD participants will be randomly subjected to the DRL control group. The light source intensity will be set at <100 lux and placed 0.6 meters away from the MDD participant. They will be required to staring at the light source for 2 seconds every 5 minutes. The DRL control group will be administered for 40 minutes each day between 7:00 AM and 10:00 AM, lasting for four weeks, 6 days per week.
干预措施: DRL (Device)
BLT experimental group
Eligible MDD participants will be randomly subjected to the BLT experimental group. The source intensity of BLT experimental group will be set at 10000 lux and placed 0.45 meters away from the MDD participant. They will be required to staring at the light source for 2 seconds every 5 minutes. The BLT experimental group will be administered for 40 minutes each day between 7:00 AM and 10:00 AM, lasting for 4 weeks, 6 days per week.
干预措施: BLT (Device)
结局指标
主要结局
Symbol Coding (SC)
时间窗: screen, baseline, weeks2, 4, and 8
The Symbol Coding (SC) is a coding paradigm adapted from the Digit Symbol Substitution Test (DSST), both of which use essentially the same method, except in reverse; instead of drawing symbols that match digits, the SC requires to write the matching digit in the blank. The task has been included as a subtest in the Brief Assessment of Cognition in Schizophrenia; in this task, subjects are required to write numerals 1-9 as matches to nonmeaningful symbols on a response sheet for 90 s, as based on a key provided to them, with higher scores reflecting better performance.
次要结局
- Young Mania Rating Scale（YMRS）(screen, baseline, weeks1, 2, 3, 4, and 8)
- Color Trails Test （CTT）(Baseline, week 2, 4 and 8)
- Hamilton Depression Rating Scale-17（HDRS-17）(screen, baseline, weeks1, 2, 3, 4, and 8)
- The 20-item Perceived Deficits Questionnaire for Depression（PDQ-D-20）(baseline, weeks 2, 4, and 8)
- The Chinese Brief Cognitive Test（CBCT）(baseline, weeks 2, 4, and 8)
- Stroop Color-Word Test (SCWT)(baseline, weeks 2, 4, and 8)
- Hopkins Verbal Learning Test-Revised (HVLT-R)(baseline, weeks 2, 4, and 8)
- Generalized Anxiety Disorder-7（GAD-7）(baseline, weeks1, 2, 3, 4, and 8)
- Quick Inventory of Depressive Symptomatology-Self-Report（QIDS-SR-16）(baseline, weeks1, 2, 3, 4, and 8)
- Pittsburgh Sleep Quality Inventory（PSQI）(baseline, weeks1, 2, 3, 4, and 8)
- Asberg Side-Effect Rating Scale for Antidepressants (SERS)(baseline, weeks1, 2, 3, 4, and 8)
- Quality of Life Enjoyment and Satisfaction Questionnaire,Short Form（Q-LES-Q-SF）(baseline, weeks1, 2, 3, 4, and 8)
- Sheehan disability scale (SDS)(baseline, weeks1, 2, 3, 4, and 8)
- Hamilton Anxiety Scale (HAMA）(Baseline, week 1, 2, 3, 4 and 8)
- Insomnia Severity Index (ISI）(Baseline, week 1, 2, 3, 4 and 8)
研究者
Xiaozhen LV
Professor
Peking University Sixth Hospital