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FMRI-neurofeedback in Depression

Primary Purpose

Depression, Unipolar

Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
fMRI-based neurofeedback
Sponsored by
Maastricht University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depression, Unipolar focused on measuring Depression, Depressive Disorder, Behavioral Symptoms, Mood Disorders, Mental Disorders, fMRI Neurofeedback

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis of a depressive disorder (ICD-10: F32 or F33) Has been on stable antidepressant medication (single or combination treatment) for at least 4 weeks Current depression (QIDS >= 17) If required to meet recruitment targets the minimum entry score will be reduced QIDS >= 13 (i.e. still corresponding to a moderate level of depression) Exclusion Criteria: Exclusion criteria for MRI (e.g. cardiac pacemaker, certain metallic implants) History of psychotic disorder bipolar disorder, or psychotic depression Current use of illegal drugs (any in the last four weeks) Current excessive alcohol consumption that interferes with daily functioning History of neurological disease that could influence the fMRI signal and/or the anatomical alignment (e.g. territorial stroke, multiple sclerosis, brain tumour)

Sites / Locations

  • Mondriaan ZorggroepRecruiting
  • Maastricht UniversityRecruiting
  • Maastricht UMC+Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Emotion network up-regulation + standard care

Standard care

Arm Description

NF protocol targeting emotion networks (NFE) (plus standard care)

Continuation of treatment as usual.

Outcomes

Primary Outcome Measures

Post-intervention score for the 30 item Inventory of Depressive Symptomatology (IDS)
30 item clinician rated depression scale (Rush et al., 1986; Rush, Gullion, Basco, Jarrett, & Trivedi, 1996)

Secondary Outcome Measures

Six month follow-up score for the 30 item Inventory of Depressive Symptomatology (IDS)
30 item clinician rated depression scale (Rush et al., 1986; Rush, Gullion, Basco, Jarrett, & Trivedi, 1996)
Post-intervention score for the Beck Depression Inventory (BDI)
Self-rated depression scale (Beck, Steer, & Brown, 1996)
Six month follow-up score for the Beck Depression Inventory (BDI)
Self-rated depression scale (Beck, Steer, & Brown, 1996)
Post-intervention score for the Hospital Anxiety and Depression Scale (HADS)
Self-rated depression and anxiety scale (Zigmond & Snaith, 1983). The questionnaire comprises 7 questions for anxiety and 7 for depression. Each scale has a minumum score of 0 and a maximum score of 21. A higher score means more severe anxiety- or depression complaints.
Six month follow-up score for the Hospital Anxiety and Depression Scale (HADS)
Self-rated depression and anxiety scale (Zigmond & Snaith, 1983). The questionnaire comprises 7 questions for anxiety and 7 for depression. Each scale has a minumum score of 0 and a maximum score of 21. A higher score means more severe anxiety- or depression complaints.
Post-intervention score for the Quality Of Life scale (QOLS)
Self-rated quality of life scale. A higher score reflects a better quality of life.
Six month follow-up score for the Quality Of Life scale (QOLS)
Self-rated quality of life scale. A higher score reflects a better quality of life.
Post-intervention score for the EuroQol research foundation questionnaire (EQ-5D-5L)
Self-rated scale of five dimensions of health (Brooks & Group, 1996)
Six month follow-up score for the EuroQol research foundation questionnaire (EQ-5D-5L)
Self-rated scale of five dimensions of health (Brooks & Group, 1996)
Experience sampling of mood states, somatic symptoms and activities using the PsyMate application
One week after baseline and one week before the end of intervention measurement partic-ipants will undergo an experience sampling procedure. Experience sampling will be acquired through the PsyMate application (https://www.psymate.eu) on patients' own or provided smartphones. Participants will thereby digitally complete a brief questionnaire including current affect (positive affect and negative affect items) as well as current context and activ-ities ("daily life activities", "persons present", "physical activity", and "events")
Post-intervention score for the Self Efficacy Scale (SES)
Self-rated scale assessing self efficacy (Sherer et al., 1982). The total scores range from 10 to 40. A higher score means more self-efficacy.
Six month follow-up score for the Self Efficacy Scale (SES)
Self-rated scale assessing self efficacy (Sherer et al., 1982). The total scores range from 10 to 40. A higher score means more self-efficacy.

Full Information

First Posted
November 28, 2022
Last Updated
March 9, 2023
Sponsor
Maastricht University
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1. Study Identification

Unique Protocol Identification Number
NCT05640089
Brief Title
FMRI-neurofeedback in Depression
Official Title
A Randomised Controlled Trial of fMRI-neurofeedback in Depression
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 25, 2023 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
April 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maastricht University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Previous studies with fMRI-neurofeedback in depression have demonstrated a good safety profile and considerable symptom reduction. The goal of this clinical trial is to compare fMRI-neurofeedback plus standard care with standard care in patients with depression. Participants will either receive standard care, or standard care plus a fMRI neurofeedback training, consisting of 5 neurofeedback training sessions. Symptom severity will be assessed before, immediately after and 6 months after the intervention.
Detailed Description
Rationale: Previous studies with fMRI-neurofeedback in depression have demonstrated a good safety profile and considerable symptom reduction but a comparison between standard care and standard care plus fMRI-neurofeedback has not yet been carried out. Objective: To assess the efficacy of fMRI-neurofeedback plus standard care in comparison with standard care in patients with depression. Study design: Single-blind RCT. Patients will be randomly allocated to fMRI-neurofeedback plus standard care or standard care. Assessments will be conducted by assessors who are blinded to group allocation. Patients will be randomised to the two groups using a block randomisation procedure (10 participants per block). Depression severity at baseline (IDS scores) will be used as minimisation variable to ensure equal severity in both groups. The study team will receive a code for group allocation. The study team and patient will be aware of the group allocation (by the nature of the study design), but assessors performing baseline, post-intervention and follow-up assessments will be blinded. During interim analyses, the analysts will remain blinded to the conditions. If the stopping criterion is reached before the maximal N, any patients already randomised will complete the study and their data will be included in the secondary analyses. Study population: Currently symptomatic adult patients with depression. Sample size calculation: A Sequential Bayes Factor (SBF) sampling plan will be used. SBF allows accumulating evidence for (or against) an effect until a certain threshold, i.e. a Bayes Factor (BF), or max N is reached. This is one main advantage compared to frequentist statistics (which is biased against the null hypothesis). Moreover, type-I and type-II error rates do not exist, allowing for flexible stopping rules. This property renders SBF a more resource efficient (in particular for small to medium effect sizes) compared to (traditional frequentist) fixed-N sampling plans. Since type-II errors do not exist in Bayesian statistics, there is no concept of statistical power as in traditional frequentist statistics. However, sensitivity analyses can be carried out a priori to help determining the sample size required to reach a pre-declared level of evidence (given an assumed effect size and a specific prior distribution) that serves as a stopping criterion, For the current sampling plan a BF >= 6 (for either the alternative or the null hypothesis) will be used as a stopping criterion, a value that is in line with recent recommendations. The analysis is carried out with an informed prior t-distribution (t(μ = 0.35, df = 3, r = 0.102)), which reflects a moderate effect size that the investigators would expect given the current design and is in line with suggested informed prior distributions in Psychology. The first interim analysis will be carried out with a minimum N=26 patients per group who have completed the primary endpoint. This minimum N is in line with recommendations for SBF sampling plans. If a BF of 6 for either the alternative or the null is hypothesis is not met, sequential sampling will be carried out with interim tests for every new patient who completes the primary endpoint until either the BF stopping criterion is met or a maximum N=38 is reached (max N). An effect size of Cohen's d = 0.6 was set as the smallest effect size of interest given the restricted resources and previously reported effect sizes reported by pre-registered randomised clinical trials of emotion self-regulation based fMRI neurofeedback. An N max of 38 per group yields 80% sensitivity to detect an effect size of 0.6 under flexible stopping as suggested by simulations (Monte Carlo with 10,000 iterations). Hence, such design is more resource efficient compared to a traditional frequentist fixed-N design (which requires N=45 to reach 80% sensitivity to detect an effect size Cohen's d = 0.6). Further, the false negative rate (i.e. the probability to accumulate erroneously sufficient evidence against the effect and stop the trial early) is only 0.1%, the false positive rate is 12%. The investigators accept this higher false positive rate (compared to the nominal 5%) given that the technology is safe to use. If the BF reaches a value BF>=3 (but smaller than 6) for either the alter-native or null hypothesis, the investigators will revaluate available resources for a potential third sampling phase with N max of 60 per group. The sampling plan thus follows recent recommendations of best practice. Intervention: FMRI-neurofeedback will be administered in 5 sessions of about 1 hour each, each including a visual stimulation protocol for the localisation of areas responsive to positive emotions and appr. 30 minutes of upregulation training of these areas by means of neurofeedback, using real-time fMRI signals. Main study parameters/endpoints: Primary outcome: symptom severity (measured by the clinician-administered Inventory of Depressive Symptomatology) after the intervention. Secondary outcomes: measures of depression, anxiety and general mental health (Beck Depression Inventory, Self-Efficacy Scale, Hospital Anxiety and Depression Scale, Quality Of Life scale and EuroQol research foundation questionnaire), predictive value of several trait measures (moderator analysis), changes in brain activation patterns measured by fMRI for the neurofeedback group. In the analysis, outcomes will be controlled for the measurements at baseline.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Unipolar
Keywords
Depression, Depressive Disorder, Behavioral Symptoms, Mood Disorders, Mental Disorders, fMRI Neurofeedback

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Emotion network up-regulation + standard care
Arm Type
Experimental
Arm Description
NF protocol targeting emotion networks (NFE) (plus standard care)
Arm Title
Standard care
Arm Type
No Intervention
Arm Description
Continuation of treatment as usual.
Intervention Type
Other
Intervention Name(s)
fMRI-based neurofeedback
Intervention Description
Participants use fMRI-based neurofeedback to train the upregulation of brain areas that respond to positive affective pictures (as identified during a functional localiser scan).
Primary Outcome Measure Information:
Title
Post-intervention score for the 30 item Inventory of Depressive Symptomatology (IDS)
Description
30 item clinician rated depression scale (Rush et al., 1986; Rush, Gullion, Basco, Jarrett, & Trivedi, 1996)
Time Frame
End of intervention: appr. 2 months after baseline
Secondary Outcome Measure Information:
Title
Six month follow-up score for the 30 item Inventory of Depressive Symptomatology (IDS)
Description
30 item clinician rated depression scale (Rush et al., 1986; Rush, Gullion, Basco, Jarrett, & Trivedi, 1996)
Time Frame
6-month follow-up
Title
Post-intervention score for the Beck Depression Inventory (BDI)
Description
Self-rated depression scale (Beck, Steer, & Brown, 1996)
Time Frame
End of intervention: appr. 2 months after baseline
Title
Six month follow-up score for the Beck Depression Inventory (BDI)
Description
Self-rated depression scale (Beck, Steer, & Brown, 1996)
Time Frame
6-month follow-up
Title
Post-intervention score for the Hospital Anxiety and Depression Scale (HADS)
Description
Self-rated depression and anxiety scale (Zigmond & Snaith, 1983). The questionnaire comprises 7 questions for anxiety and 7 for depression. Each scale has a minumum score of 0 and a maximum score of 21. A higher score means more severe anxiety- or depression complaints.
Time Frame
End of intervention: appr. 2 months after baseline
Title
Six month follow-up score for the Hospital Anxiety and Depression Scale (HADS)
Description
Self-rated depression and anxiety scale (Zigmond & Snaith, 1983). The questionnaire comprises 7 questions for anxiety and 7 for depression. Each scale has a minumum score of 0 and a maximum score of 21. A higher score means more severe anxiety- or depression complaints.
Time Frame
6-month follow-up
Title
Post-intervention score for the Quality Of Life scale (QOLS)
Description
Self-rated quality of life scale. A higher score reflects a better quality of life.
Time Frame
End of intervention: appr. 2 months after baseline
Title
Six month follow-up score for the Quality Of Life scale (QOLS)
Description
Self-rated quality of life scale. A higher score reflects a better quality of life.
Time Frame
6-month follow-up
Title
Post-intervention score for the EuroQol research foundation questionnaire (EQ-5D-5L)
Description
Self-rated scale of five dimensions of health (Brooks & Group, 1996)
Time Frame
End of intervention: appr. 2 months after baseline
Title
Six month follow-up score for the EuroQol research foundation questionnaire (EQ-5D-5L)
Description
Self-rated scale of five dimensions of health (Brooks & Group, 1996)
Time Frame
6-month follow-up
Title
Experience sampling of mood states, somatic symptoms and activities using the PsyMate application
Description
One week after baseline and one week before the end of intervention measurement partic-ipants will undergo an experience sampling procedure. Experience sampling will be acquired through the PsyMate application (https://www.psymate.eu) on patients' own or provided smartphones. Participants will thereby digitally complete a brief questionnaire including current affect (positive affect and negative affect items) as well as current context and activ-ities ("daily life activities", "persons present", "physical activity", and "events")
Time Frame
1 week after baseline, 1 week before the end of intervention measurement
Title
Post-intervention score for the Self Efficacy Scale (SES)
Description
Self-rated scale assessing self efficacy (Sherer et al., 1982). The total scores range from 10 to 40. A higher score means more self-efficacy.
Time Frame
End of intervention: appr. 2 months after baseline
Title
Six month follow-up score for the Self Efficacy Scale (SES)
Description
Self-rated scale assessing self efficacy (Sherer et al., 1982). The total scores range from 10 to 40. A higher score means more self-efficacy.
Time Frame
6-month follow-up
Other Pre-specified Outcome Measures:
Title
Ability to self-regulate the target region-of-interest during neurofeedback training
Description
Determine whether participants are able to modulate their BOLD activity in keeping with the neurofeedback
Time Frame
Each scanning session (appr. 2 months: session 1: week 1; session 2: week 2; session 3: week 3; session 4: week 4; session 5: week 8)
Title
Changes in functional parameters (as measured by fMRI) of emotion networks over the course of the intervention
Description
Analysis of fMRI data
Time Frame
Each scanning session (appr. 2 months: session 1: week 1; session 2: week 2; session 3: week 3; session 4: week 4; session 5: week 8)
Title
Brain network activity during neurofeedback training (fMRI analysis)
Description
Determining changes in brain networks (e.g. default mode network)
Time Frame
Each scanning session (appr. 2 months: session 1: week 1; session 2: week 2; session 3: week 3; session 4: week 4; session 5: week 8)
Title
Changes in Profile of Mood States (POMS) after neurofeedback sessions
Description
Measure to address any imminent changes in mood state
Time Frame
Before and after each scanning session (appr. 2 months: session 1: week 1; session 2: week 2; session 3: week 3; session 4: week 4; session 5: week 8)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of a depressive disorder (ICD-10: F32 or F33) Has been on stable antidepressant medication (single or combination treatment) for at least 4 weeks Current depression (QIDS >= 17) If required to meet recruitment targets the minimum entry score will be reduced QIDS >= 13 (i.e. still corresponding to a moderate level of depression) Exclusion Criteria: Exclusion criteria for MRI (e.g. cardiac pacemaker, certain metallic implants) History of psychotic disorder bipolar disorder, or psychotic depression Current use of illegal drugs (any in the last four weeks) Current excessive alcohol consumption that interferes with daily functioning History of neurological disease that could influence the fMRI signal and/or the anatomical alignment (e.g. territorial stroke, multiple sclerosis, brain tumour)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David E Linden, Prof.
Phone
+31 43 3881021
Email
david.linden@maastrichtuniversity.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David E Linden, Prof.
Organizational Affiliation
Professor of Translational Neuroscience
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mondriaan Zorggroep
City
Maastricht
ZIP/Postal Code
6226NB
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rob Havermans, Dr.
Facility Name
Maastricht University
City
Maastricht
ZIP/Postal Code
6229ER
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Maastricht UMC+
City
Maastricht
ZIP/Postal Code
6229HX
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bart Rutten, Professor

12. IPD Sharing Statement

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FMRI-neurofeedback in Depression

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