Clinical trial NCT05322863: High-definition Transcranial Direct Current Stimulation (HD-tDCS) in Late-life Depression (LLD)
Official title: High-definition Transcranial Direct Current Stimulation (HD-tDCS) as Augmentation Therapy in Late-life Depression (LLD) With Suboptimal Response to Treatment - Double-blinded Randomized Sham-controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Depression in Old Age
Keywords: augmentation therapy
late-life depression
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2022-04-12
Enrollment: 58
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine the efficacy of a 2-week daily programme (10 sessions) of HD-tDCS to augment antidepressant therapy in subjects with late-life depression who had residual depressive symptoms despite adequate dosage and duration of antidepressant therapy.

Detailed description: Background:

Hong Kong is facing a significant challenge in ageing population. A significant proportion of older adults suffered from depression. As the local population is ageing rapidly, the burden of late-life depression (LLD) will continue to increase. LLD is associated with a poorer long term prognosis, a more chronic course and a higher relapse rate comparing with adult-onset depression. Treatment response towards medication is unsatisfactory. Over 50% of patients with LLD do not achieve symptomatic remission. With the growing ageing population in Hong Kong, LLD becomes a pressing problem. The mainstream treatment of LLD is antidepressant and electroconvulsive therapy (ECT). Despite these methods being shown to be effective, there are limitations in each of these treatments. A new treatment option or augmentation therapy would be needed to improve the treatment response in LLD. Transcranial direct current stimulation (tDCS) is a non-invasive neurostimulation method. It applies a weak, direct electric current over the scalp region. It is a very safe intervention tool. It exerts the treatment effect probably through the change in the activity of neurons and modulation in synaptic release probability uptake and sensitivity. It enhances the long-term plasticity (LTP) and changes the rate of neurotransmitter release. High-definition tDCS (HD-tDCS) allows for more accuracy and focus on targeting the specific brain region. Recent evidence suggested that tDCS and serotonin enhance each other's function. Controversial outcomes were reported in previous randomised controlled trials (RCT) focusing on adult patients with depression. There is no RCT done among patients with LLD. An open-label pilot study was conducted by our team in 2018 which showed a significant improvement in depressive symptoms and mild improvement in cognitive domains after 2 weeks of HD-tDCS intervention.

Objectives:

This study is a double-blinded randomized sham-controlled trial to test the effectiveness of HD-tDCS as augmentation therapy for antidepressants in patients with LLD. The investigators hypothesized that active HD-tDCS is significantly more effective than sham control in reducing depressive symptoms.

Design:

The current study is a 2-week intervention trial of HD-tDCS with 4-week and 12-week post-intervention observation. All eligible participants must receive at least four weeks of antidepressant treatment before the tDCS intervention. Then they will be randomised to receive either active HD-tDCS (a-HD-tDCS) or sham-HD-tDCS (s-HD-tDCS) intervention for two weeks with five sessions per week. Both the participants and the investigators responsible for assessments and data analysis will be blinded to the group allocation. Total ten sessions HD-tDCS will be delivered. Each session would last for 30 minutes. After HD-tDCS intervention, participants would continue their medications for at least for 12 more weeks until all post-intervention assessments are complete.

Data Analysis:

Primary outcome and secondary outcomes assessment would be carried out at baseline, immediately after the intervention and follow

* up assessments at 4 and 12 weeks. The primary outcome will be the change of Hamilton depression rating scale (HAM-D-17). Secondary outcomes will include cognitive assessments, anxiety symptoms, daily functioning and adverse effects of the intervention. Intention-to
* treat analysis would be carried out. Intention-to-treat analysis would be carried out.

Significance:

The result of the current study would provide further data on the effectiveness of HD-tDCS as augmentative therapy with antidepressants in LLD patients.

Eligibility criteria: Inclusion Criteria:

1. 60 years of age or above
2. Right-handedness, as determined by the Edinburgh Handedness Inventory (to homogenise neuroanatomical targeting)
3. Chinese ethnicity
4. Fulfil the criteria of Major Depressive Disorder (single or recurrent episode) and in partial remission, defined by the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
5. Presence of mild to severe level of depressive symptoms measured and defined by HAM-D-17 score ≥8 and ≤ 52\[22\]
6. Suboptimal treatment response with at least one adequate antidepressant trial defined as full or best tolerated doses at least 6 weeks
7. Stable dosage of antidepressants or other treatments for depression in recent 4 weeks
8. Valid informed written consent

Exclusion Criteria:

1. A DSM-5 diagnosis other than Depressive Disorders (e.g., bipolar and related disorders, schizophrenia spectrum and other psychotic disorders).
2. A Hong Kong Chinese version of the Montreal Cognitive Assessment (HK-MoCA) score below the second percentile according to the subject's age and education level (to exclude subjects with existing dementia)
3. Alcohol or substance dependence
4. Active suicidal ideation or a suicide attempt within the past month
5. Concomitant unstable medical condition or major neurological conditions
6. Significant communication impairment

Primary outcomes:
measure: Change in the Depressive symptoms
timeFrame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Secondary outcomes:
measure: Change in the Global Cognition
timeFrame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
measure: Change in the Working Memory
timeFrame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
measure: Change in the Executive Functioning
timeFrame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
measure: Change in the Verbal Fluency
timeFrame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
measure: Change in the Attention
timeFrame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
measure: Change in the Anxiety symptoms
timeFrame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
measure: Change in Daily functioning
timeFrame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
measure: Change in Adverse effects and risk indicators
timeFrame: Assessed immediately after each (in total 10) individual treatment session.
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Department of Psychiatry, University of Hong Kong
Study officials:
affiliation: The University of Hong Kong
name: Pak Wing Calvin Cheng
role: PRINCIPAL_INVESTIGATOR
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