Efficacy of Bright Light Therapy on Cognitive Impairment in Major Depressive Disorder and Its Neuroimaging Mechanisms: Protocol for a Randomised Controlled Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство BLT
  Using a hybrid white light box with independent intellectual property rights, with an intensity of 10000lux and a main wavelength of 476.4nm
• Устройство DRL
  Using a dim red light box as the placebo, with an intensity of \<100lux and a main wavelength of 690.4nm

Первичные конечные точки

• Symbol Coding (SC) [Срок оценки: screen, baseline, weeks2, 4, and 8]

Вторичные конечные точки (12)

• Hamilton Depression Rating Scale-17（HDRS-17） [Срок оценки: screen, baseline, weeks1, 2, 3, 4, and 8]
• The 20-item Perceived Deficits Questionnaire for Depression（PDQ-D-20） [Срок оценки: baseline, weeks 2, 4, and 8]
• The Chinese Brief Cognitive Test（CBCT） [Срок оценки: baseline, weeks 2, 4, and 8]
• Stroop Color-Word Test (SCWT) [Срок оценки: baseline, weeks 2, 4, and 8]
• Hopkins Verbal Learning Test-Revised (HVLT-R) [Срок оценки: baseline, weeks 2, 4, and 8]
• Generalized Anxiety Disorder-7（GAD-7） [Срок оценки: baseline, weeks1, 2, 3, 4, and 8]
• Quick Inventory of Depressive Symptomatology-Self-Report（QIDS-SR-16） [Срок оценки: baseline, weeks1, 2, 3, 4, and 8]
• Pittsburgh Sleep Quality Inventory（PSQI） [Срок оценки: baseline, weeks1, 2, 3, 4, and 8]
• Young Mania Rating Scale（YMRS） [Срок оценки: screen, baseline, weeks1, 2, 3, 4, and 8]
• Asberg Side-Effect Rating Scale for Antidepressants (SERS) [Срок оценки: baseline, weeks1, 2, 3, 4, and 8]
• Quality of Life Enjoyment and Satisfaction Questionnaire,Short Form（Q-LES-Q-SF） [Срок оценки: baseline, weeks1, 2, 3, 4, and 8]
• Sheehan disability scale (SDS) [Срок оценки: baseline, weeks1, 2, 3, 4, and 8]

Критерии участия

The inclusion and exclusion criteria 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Peking University Sixth Hospital — Пекин
• Yan'an Third People's Hospital — Yanan

Идентификаторы

NCT: NCT07508215 · 7262156

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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