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Neurofeedback In Treatment Resistant Depression

Primary Purpose

Depression, Neurofeedback

Status
Terminated
Phase
Not Applicable
Locations
Korea, Republic of
Study Type
Interventional
Intervention
neurofeedback augmentation
treatment as usual
psychotherapy placebo sessions
Sponsored by
Yeungnam University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Depression focused on measuring Treatment-resistant depression, Neurofeedback, Functional recovery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Diagosis with MDD according to the DSM-IV-TR criteria for MDD, and especially treatment-resistant MDD (Hamilton Rating Scale for Depression [HAM-D] score ⩾14) despite adequate antidepressant therapy)

Exclusion Criteria:

  • Psychosis
  • Bipolar disorder
  • Brain injury
  • Clinically diagnosed neurological disorder
  • Convulsive disorder
  • Pregnancy

Sites / Locations

  • Yeungnam University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

No Intervention

Arm Label

neurofeedback augmentation group

medication-only (treatment as usual, TAU) group

healthy controls

Arm Description

The neurofeedback augmentation group was asked to participate in 12 weeks of combined therapy of medication and 12-24 sessions of neurofeedback training. The neurofeedback protocol was determined considering the patient's main symptoms. Patients in the neurofeedback augmentation group received sensorimotor rhythm (SMR) beta or beta training for 30 minutes, and then alpha/theta (A/T) training for 30 minutes in each session.

To reduce the impact of confounding factors, the medication-only (treatment as usual, TAU) group visited at the same schedule as neurofeedback augmentation group and received psychotherapy placebo sessions instead of neurofeedback training sessions. These sessions included psychological assessment and supportive psychotherapy. The medication-only (treatment as usual, TAU) group maintained the same medication use as that before the study.

The healthy controls provided blood samples using the same procedure at baseline only.

Outcomes

Primary Outcome Measures

Changes in Hamilton Rating Scale for Depression [HAM-D] score at baselline and the 1-, 4-, and 12-week time points
The HAM-D is an observer rating scale and 1 of the most widely used measures of depressive disorder. This scale composed of 17 items, and it has been used to assess the therapeutic effect as well as the severity of depression. Total score is 52, where higher scores indicating more severe depression. Hamilton considered Total score of 8-13 mild range, 14-18 moderate, 18-22 severe, and 23 or higher very severe.

Secondary Outcome Measures

Changes in Beck Depression Inventory- II (BDI-II) scores at baselline and the 1-, 4-, and 12-week time points
The BDI is self-report scale designed to evaluate the presence and severity of depressive symptoms. It is consisted of 21 items including cognitive, emotional, motivative, and physical symptoms of depression. Each question is scored from 0 to 3 points, and the total score ranges from 0 to 63, indicating the higher the total scores, the more severe the depression. It is considered total score of 0-9 minimal range, 10-15 mild, 16-23 moderate, and 24-63 severe.
Changes in Sheehan Disability Scale (SDS) score at baselline and the 1-, 4-, and 12-week time points
The SDS is a self-report scale designed by Sheehan to assess the severity of functional impairment. This scale consists of 3 items, and each item is divided into 11 levels from 0 to 10 points. It is considered 0 point: none, 1-3 points: mild, 4-6 points: moderate, and 7-10 points: severe. Total score ranges from 0 to 30 and means that the higher the total scores, the more severe the functional impairment.
Changes in Clinical Global Impression-Severity (CGI-S) at baselline and the 1-, 4-, and 12-week time points
The CGI-S is a single-item scale composed of 7 levels ranging from maximum score of 7 to normal state of 1. This scale is a measure by which the evaluator comprehensively assesses the severity of mental illness regardless of diagnosis.
Comparisons of serum brain-derived neurotrophic factor (BDNF) level between baseline and the 12-week time point among groups
Brain-derived neurotrophic factor (BDNF) acts on certain neurons of the central nervous system and the peripheral nervous system. It helps support the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. Previous studies have suggested the presence of an etiological link between the development of depression and BDNF.
Type and number of adverse events
adverse events
Changes in valuation of 5 level version of European Quality of Life Questionnaire 5-Dimensional Classification (EQ-5D-5L) (converted tariff score)
The EQ-5D-5L was developed by the EuroQol Group, and is used to assess 5 dimensions: mobility, self care, usual activity, pain/discomfort, and anxiety/depression. Each dimension is consisted of 5 levels, so total 3125 health states can be evaluated. The valuation of EQ-5D-5L (converted tariff score) is an index score calculated by applying weight to each of the 5 EQ-5D-5L questionnaires to provide a comprehensive summary of health-related quality of life. The resulting set of tariff is widely used to calculate preferences for EQ-5D-5L health states. As EQ-5D-5L is translated according to the culture and situation of each country, EQ-5D-5L tariffs may differ at each country. The index score is valued from 0 to 1, and the higher scores indicate the higher quality of life for the patients. In this study, EQ-5D-5L tariffs (index values) were calculated according to the [The EQ-5D-5L valuation study in Korea.].
Changes in response and remission rate of Hamilton Rating Scale for Depression [HAM-D] score
Remission was defined as achieving a HAM-D score below 7, and response was defined as a 50% or greater reduction in HAM-D score from baseline.

Full Information

First Posted
August 22, 2019
Last Updated
June 29, 2020
Sponsor
Yeungnam University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04078438
Brief Title
Neurofeedback In Treatment Resistant Depression
Official Title
Neurofeedback Treatment on Depressive Symptoms and Functional Recovery in Treatment-resistant Patients With Major Depressive Disorder: an Open-label Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Terminated
Why Stopped
Because of researcher foreign training
Study Start Date
June 27, 2014 (Actual)
Primary Completion Date
December 27, 2019 (Actual)
Study Completion Date
February 8, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Yeungnam University Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The investigators evaluate the effects of neurofeedback as an augmentation treatment on depressive symptoms and functional recovery in patients with treatment-resistant depression (TRD). TRD patients are assigned to the neurofeedback augmentation group and the medication-only (treatment as usual, TAU) group. The neurofeedback augmentation group underwent combined therapy comprising medication and 12-24 sessions of neurofeedback training for 12 weeks. To assess the serum levels of brain-derived neurotrophic factor (BDNF) in both groups, a pre- and post-treatment blood samples are obtained. Patients are evaluated using the Hamilton Depression Rating Scale (HAM-D), Beck Depression Inventory (BDI), Clinical Global Impression-Severity (CGI-S), 5-level version of European Quality of Life Questionnaire 5-Dimensional Classification (EQ-5D-5L), and Sheehan Disability Scale (SDS) at baseline, and at the 1-, 4-, and 12-week.
Detailed Description
Major depressive disorder (MDD) is a severely disabling disorder resulting in the deterioration of daily function and lowering quality of life. The lifetime prevalence of depression is 10-15%, and the annual prevalence of MDD in the United States is approximately 7%. The World Health Organization has reported that MDD is expected to be the top disease in terms of global burden by 2030. Fifty percent of patients with depressive disorder have a chronic disease course, and 20% of such patients have insufficient responses to treatment despite the use of antidepressant medication. In addition, although antidepressants have been shown to be effective, residual symptoms may continue by stopping the medication early due to inconvenient side effects of the medication. Sixty percent of patients with depressive disorder have poorer executive function. Patients with depressive disorder are continuously affected by deficits in social functioning, such as interpersonal relationships and job adaptation, even if some of their symptoms are improved by medication. Therefore, various additional treatments other than antidepressant treatment have been tried to improve residual depressive symptoms and the remission rate. Brain waves have been used to measure brain activity and previous studies have reported that different brain waves reflect different brain states, including moods. Neurofeedback is a type of electroencephalography (EEG) training that allows individuals to change the levels of particular types of brain waves displayed on a computer by operational conditioning. EEG studies showed that the neurofeedback is capable of generating long term changes in the spectral EEG topography, while neuroimaging studies represented the neuroplastic effects from neurofeedback treatment. Neurofeedback is an alternative approach that aims to help individuals alter brain activation without introducing electrical or magnetic activity, or pharmacological compounds into the brain, hence preventing the brain from becoming dependent on outside influences for better functioning. It is noninvasive method and there's no report of even minor side effects. Neurofeedback may be considered a new augmentation treatment for patients with treatment-resistant depression (TRD), even after the use of antidepressants. Some studies have reported improvements in both depressive symptoms and executive function following neurofeedback treatment. A recent article insisted that neurofeedback treatment for depression as having "revealed promising effects in recent clinical trials". However, most such studies have been case reports or uncontrolled studies, and the mechanism underlying the treatment effects of neurofeedback are still unclear. In addition, there has been no study of neurofeedback on depressive symptoms and functional recovery in patients with TRD. Brain-derived neurotrophic factor (BDNF) acts on certain neurons of the central nervous system and the peripheral nervous system. It helps support the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. Previous studies have suggested the presence of an etiological link between the development of depression and BDNF. However, no studies have examined the association between neurofeedback and changes in BDNF level. The purpose of this pilot study was to evaluate the effects of neurofeedback as an augmentation treatment on depressive symptoms and functional recovery in patients with TRD. The investigators also aimed to identify the usefulness of BDNF as a biomarker for neurofeedback by examining changes in the BDNF level before vs. after treatment in the neurofeedback treatment and medication-only (treatment as usual, TAU) groups.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Neurofeedback
Keywords
Treatment-resistant depression, Neurofeedback, Functional recovery

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
neurofeedback augmentation group
Arm Type
Experimental
Arm Description
The neurofeedback augmentation group was asked to participate in 12 weeks of combined therapy of medication and 12-24 sessions of neurofeedback training. The neurofeedback protocol was determined considering the patient's main symptoms. Patients in the neurofeedback augmentation group received sensorimotor rhythm (SMR) beta or beta training for 30 minutes, and then alpha/theta (A/T) training for 30 minutes in each session.
Arm Title
medication-only (treatment as usual, TAU) group
Arm Type
Active Comparator
Arm Description
To reduce the impact of confounding factors, the medication-only (treatment as usual, TAU) group visited at the same schedule as neurofeedback augmentation group and received psychotherapy placebo sessions instead of neurofeedback training sessions. These sessions included psychological assessment and supportive psychotherapy. The medication-only (treatment as usual, TAU) group maintained the same medication use as that before the study.
Arm Title
healthy controls
Arm Type
No Intervention
Arm Description
The healthy controls provided blood samples using the same procedure at baseline only.
Intervention Type
Device
Intervention Name(s)
neurofeedback augmentation
Intervention Description
Neurofeedback training was performed using a Neurocybernetics EEG Biofeedback system (Neurocybernetics Inc., Encino, CA, USA). The neurofeedback protocol was determined by the neurofeedback team, which included 3 psychiatrists, in consideration of the patient's main symptoms. The neurofeedback augmentation group was asked to participate in 12 weeks of combined therapy of medication and 12-24 sessions of neurofeedback training. Patients in the neurofeedback augmentation group received sensorimotor rhythm (SMR) beta or beta training for 30 minutes, and then alpha/theta (A/T) training for 30 minutes in each session. To reduce the impact of confounding factors, the medication-only (treatment as usual, TAU) group visited at the same schedule as neurofeedback augmentation group and received psychotherapy placebo sessions. The medication-only (treatment as usual, TAU) group maintained the same medication use as that before the study.
Intervention Type
Drug
Intervention Name(s)
treatment as usual
Other Intervention Name(s)
medication
Intervention Description
The neurofeedback augmentation group and the medication-only group maintained the same medication use as that before the study.
Intervention Type
Other
Intervention Name(s)
psychotherapy placebo sessions
Intervention Description
To reduce the impact of confounding factors, the medication-only (treatment as usual, TAU) group visited at the same schedule as neurofeedback augmentation group and received psychotherapy placebo sessions instead of neurofeedback training sessions. These sessions included psychological assessment and supportive psychotherapy.
Primary Outcome Measure Information:
Title
Changes in Hamilton Rating Scale for Depression [HAM-D] score at baselline and the 1-, 4-, and 12-week time points
Description
The HAM-D is an observer rating scale and 1 of the most widely used measures of depressive disorder. This scale composed of 17 items, and it has been used to assess the therapeutic effect as well as the severity of depression. Total score is 52, where higher scores indicating more severe depression. Hamilton considered Total score of 8-13 mild range, 14-18 moderate, 18-22 severe, and 23 or higher very severe.
Time Frame
at baseline, and at the 1-, 4-, and 12-week time points.
Secondary Outcome Measure Information:
Title
Changes in Beck Depression Inventory- II (BDI-II) scores at baselline and the 1-, 4-, and 12-week time points
Description
The BDI is self-report scale designed to evaluate the presence and severity of depressive symptoms. It is consisted of 21 items including cognitive, emotional, motivative, and physical symptoms of depression. Each question is scored from 0 to 3 points, and the total score ranges from 0 to 63, indicating the higher the total scores, the more severe the depression. It is considered total score of 0-9 minimal range, 10-15 mild, 16-23 moderate, and 24-63 severe.
Time Frame
at baseline, and at the 1-, 4-, and 12-week time points.
Title
Changes in Sheehan Disability Scale (SDS) score at baselline and the 1-, 4-, and 12-week time points
Description
The SDS is a self-report scale designed by Sheehan to assess the severity of functional impairment. This scale consists of 3 items, and each item is divided into 11 levels from 0 to 10 points. It is considered 0 point: none, 1-3 points: mild, 4-6 points: moderate, and 7-10 points: severe. Total score ranges from 0 to 30 and means that the higher the total scores, the more severe the functional impairment.
Time Frame
at baseline, and at the 1-, 4-, and 12-week time points.
Title
Changes in Clinical Global Impression-Severity (CGI-S) at baselline and the 1-, 4-, and 12-week time points
Description
The CGI-S is a single-item scale composed of 7 levels ranging from maximum score of 7 to normal state of 1. This scale is a measure by which the evaluator comprehensively assesses the severity of mental illness regardless of diagnosis.
Time Frame
at baseline, and at the 1-, 4-, and 12-week time points.
Title
Comparisons of serum brain-derived neurotrophic factor (BDNF) level between baseline and the 12-week time point among groups
Description
Brain-derived neurotrophic factor (BDNF) acts on certain neurons of the central nervous system and the peripheral nervous system. It helps support the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. Previous studies have suggested the presence of an etiological link between the development of depression and BDNF.
Time Frame
at baseline, and 12-week time points.
Title
Type and number of adverse events
Description
adverse events
Time Frame
through study completion, an average of 12 weeks
Title
Changes in valuation of 5 level version of European Quality of Life Questionnaire 5-Dimensional Classification (EQ-5D-5L) (converted tariff score)
Description
The EQ-5D-5L was developed by the EuroQol Group, and is used to assess 5 dimensions: mobility, self care, usual activity, pain/discomfort, and anxiety/depression. Each dimension is consisted of 5 levels, so total 3125 health states can be evaluated. The valuation of EQ-5D-5L (converted tariff score) is an index score calculated by applying weight to each of the 5 EQ-5D-5L questionnaires to provide a comprehensive summary of health-related quality of life. The resulting set of tariff is widely used to calculate preferences for EQ-5D-5L health states. As EQ-5D-5L is translated according to the culture and situation of each country, EQ-5D-5L tariffs may differ at each country. The index score is valued from 0 to 1, and the higher scores indicate the higher quality of life for the patients. In this study, EQ-5D-5L tariffs (index values) were calculated according to the [The EQ-5D-5L valuation study in Korea.].
Time Frame
at baseline, and at the 1-, 4-, and 12-week time points.
Title
Changes in response and remission rate of Hamilton Rating Scale for Depression [HAM-D] score
Description
Remission was defined as achieving a HAM-D score below 7, and response was defined as a 50% or greater reduction in HAM-D score from baseline.
Time Frame
at baseline, and at the 1-, 4-, and 12-week time points.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Diagosis with MDD according to the DSM-IV-TR criteria for MDD, and especially treatment-resistant MDD (Hamilton Rating Scale for Depression [HAM-D] score ⩾14) despite adequate antidepressant therapy) Exclusion Criteria: Psychosis Bipolar disorder Brain injury Clinically diagnosed neurological disorder Convulsive disorder Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eun-Jin Cheon, M.D., Ph.D
Organizational Affiliation
Yeungnam University Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Yeungnam University Hospital
City
Daegu
ZIP/Postal Code
42415
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
31674161
Citation
Lee YJ, Lee GW, Seo WS, Koo BH, Kim HG, Cheon EJ. Neurofeedback Treatment on Depressive Symptoms and Functional Recovery in Treatment-Resistant Patients with Major Depressive Disorder: an Open-Label Pilot Study. J Korean Med Sci. 2019 Nov 4;34(42):e287. doi: 10.3346/jkms.2019.34.e287.
Results Reference
derived

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Neurofeedback In Treatment Resistant Depression

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