High-definition Transcranial Direct Current Stimulation (HD-tDCS) in Late-life Depression (LLD)

April 11, 2022 updated by: Dr. Cheng Pak Wing, Calvin, The University of Hong Kong

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

58

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Pak Wing Calvin Cheng
  • Phone Number: 22554486
  • Email: chengpsy@hku.hk

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Department of Psychiatry, University of Hong Kong
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: active HD-tDCS
The participants will be instructed to relax during the first 5 minutes of the session while the equipment is set up. A mild stimulation (with a level of only 2 milliamps stimulation) will be delivered for 20 minutes, with the current gradually increased and decreased over 30 seconds. The patients will be instructed to relax and remain motionless during the intervention. The administrator will closely monitor the impedance throughout each session and record any side effects experienced by the participants. The participants will be allowed 5 minutes of rest after the intervention and will be actively asked about any discomfort. Each session will last around 30 minutes, with a total of 10 sessions (two consecutive weeks of treatment for 5 days per week).
Device: High-definition Transcranial Direct Current Stimulation
The HD-tDCS will be administered by the program device called Starstim (Neuroelectrics). All participants will receive the treatment by using the same model of device. The HD-tDCS device can be portable and controlled wirelessly via computer software developed by the manufacturer. The montages will be a '4 × 1 ring set-up', which is the most commonly used HD-tDCS setting. The centre anode electrode is surrounded by four return cathode electrodes. The anode will be placed over the left dorsal lateral prefrontal cortex. Conductive electrode gel will be applied on the scalp at all designated electrode stimulation areas. A cap appropriate for each participants' head size will be used to ensure that the electrodes are secured in place. Impedance checks will be performed using the Starstim software before each treatment session.
Sham Comparator: sham-HD-tDCS
The procedure for sham stimulation will be identical, except that the current will be gradually ramped down to zero after the first 30 s, thus giving the same initial sensation of HD-tDCS. The stimulator will be programmed to switch the current on and off, so no intervention by the operator will be required. The computer will be placed behind the subjects' heads so they cannot see the readout.
Device: High-definition Transcranial Direct Current Stimulation
The HD-tDCS will be administered by the program device called Starstim (Neuroelectrics). All participants will receive the treatment by using the same model of device. The HD-tDCS device can be portable and controlled wirelessly via computer software developed by the manufacturer. The montages will be a '4 × 1 ring set-up', which is the most commonly used HD-tDCS setting. The centre anode electrode is surrounded by four return cathode electrodes. The anode will be placed over the left dorsal lateral prefrontal cortex. Conductive electrode gel will be applied on the scalp at all designated electrode stimulation areas. A cap appropriate for each participants' head size will be used to ensure that the electrodes are secured in place. Impedance checks will be performed using the Starstim software before each treatment session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Depressive symptoms
Time Frame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
the clinical response rate and the remission rate as measured with the HAM-D-17. A clinical response will be defined as a reduction of 50% or more in the HAM-D-17 score. A HAM-D-17 score of 7 or less will be used as an indicator of remission. Scores range from 0 to 52, with higher scores indicating more severe depression.
Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Global Cognition
Time Frame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Using the Hong Kong Chinese version of the Montreal Cognitive Assessment. The total score ranges from 0-30 with higher scores indicating better cognition.
Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Change in the Working Memory
Time Frame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Measured by forward and backward digit span.
Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Change in the Executive Functioning
Time Frame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Measured by the Trail Making Test Parts A and B.
Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Change in the Verbal Fluency
Time Frame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Measured by category verbal fluency test.
Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Change in the Attention
Time Frame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Measured by the Stroop test.
Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Change in the Anxiety symptoms
Time Frame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Measured by the Hamilton Anxiety Rating Scale (HAMA). It is a widely used clinician-rated scale ranging from 0-56, with higher marks represent more severe in anxiety symptoms.
Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Change in Daily functioning
Time Frame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Instrumental activities of daily living will be assessed with the Hong Kong Chinese version of the Lawton Instrumental Activities of Daily Living Scale. The daily functioning would be assessed with a total score ranging from 0 to 27. A higher score indicates a higher functioning level.
Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
Change in Adverse effects and risk indicators
Time Frame: Assessed immediately after each (in total 10) individual treatment session.
checklist of potential adverse effects associated with t-DCS administration will be generated from the available literature. Risk indicators such as suicidal risk or severe self-neglect that would necessitate immediate changes to treatment will be directly assessed according to the risk and needs.
Assessed immediately after each (in total 10) individual treatment session.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Investigators

  • Principal Investigator: Pak Wing Calvin Cheng, The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 22, 2021

Primary Completion (Anticipated)

February 22, 2023

Study Completion (Anticipated)

February 22, 2024

Study Registration Dates

First Submitted

March 24, 2022

First Submitted That Met QC Criteria

April 11, 2022

First Posted (Actual)

April 12, 2022

Study Record Updates

Last Update Posted (Actual)

April 12, 2022

Last Update Submitted That Met QC Criteria

April 11, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20191119

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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