Neuro MRI Biomarkers for Treatment Navigation in Depression

NCT05701267 | Completed

• 1 other identifier: Neurotrend_001
• Study Type: observational
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

Background of the study: Major depressive disorder is a severe neuropsychiatric condition that affects approximately 15% to 18% of people worldwide during their lifetime (Malhi \& Mann, 2018). Selection of the optimal treatment is difficult. A certain correlation (functional / structural, vascular or a mix of both) is expected between clinical data (obtained from psychometric tests such as the HDRS and psychiatric evaluations) and MRI parameters (functional activity, structural connectivity, anatomical variations, perfusion / diffusion etc.). Objective of the study: Identification of MRI-based biomarkers to predict clinical outcome of major depressive disorder in comparison with healthy controls. Outcome is defined by level of depressive and cognitive symptomatology and related comorbidity. Study design: An independent treating physician will inform a potentially eligible patient and ask whether he/she is interested in voluntary participation in the study. If he/she is interested, the independent treating physician will refer the patient to one of the clinicians from the GGz who is also involved in the Neurotrend study for further steps such as providing the information letter / informed consent and scheduling an intake interview at least one week after receiving all necessary information. Healthy controls will be recruited through public advertisement and via the website www.neurotrend.nl. Pilot subjects will be recruited from the Eindhoven University community and via the website www.neurotrend.nl. Both groups, healthy controls and pilot subjects, will have at least one week to consider and decide on participation. One week later an intake session will take place in which the inclusion and exclusion criteria will be checked. During this session, patients can also ask questions about the study and the informed consent will be signed if the participant is willing to participate voluntarily in the study. Subsequently at the end of the intake session, a starting (baseline) date will be planned for this participant . The actual participation starts at baseline. In total, 120 depressed patients and 60 healthy controls will participate in the study. Each participant visits Kempenhaeghe twice, whereby each session, is dedicated to complete questionnaires and cognitive tests, such as memory tasks and eye tracking. In the last hour, the participant will be scanned (MRI). Two weeks before each visit, the participant has to fill in some questionnaires that have been sent to the participant. Study population: 120 patients with major depressive disorder and 60 healthy controls\*. \* Inclusion of up to 30 healthy "pilot" participants for technical evaluation. See above. Primary study parameters/outcome of the study:

• Hamilton Depression Rating Scale (HDRS) scores
• Treatment / medication usage
• MRI metrics (varies per MRI modality, an example is volume per region for a T1-weighted scan and fractional anisotropy for diffusion-weighted scans). Secondary study parameters/outcome of the study (if applicable):
• Scores of psychometric assessments (e.g. STAI-DY1 - anxiety score)
• Scores of cognitive assessments (e.g. average response time for the eye-tracking task) Nature and extent of the burden and risks associated with participation, benefit and group relatedness (if applicable): The participant burden is low and is divided into an intake session and two research sessions. The MRI scan is non-invasive, and subjects can indicate that they want to stop the scan at any time during the scan by squeezing a type of balloon that will lie next to the subject in the case that they feel uncomfortable or for any other reason. Subjects with MRI contraindications (e.g. claustrophobia, pregnancy or implants not suitable for MRI) are already excluded in advance and will therefore not participate in the study at all. Mostly, the subjects will lie still during the scan, except for one affective task in which they will be asked to match different emotional faces for about 5 minutes.The cognitive tests will only consist of memory, reaction speed, attention, and processing speed tasks which in total, do not last more than 30 minutes. The risks of the MRI scanner (CE-marked) are minimal.

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (28)

• Basline brain region (subfield) volumes

  Volumes are extracted from T1w and T2w scans. Subfield volumes of the hippocampus and amygdala can be extracted from a high-resolution T2w image.

  baseline

• 1-Year brain region (subfield) volumes

  Volumes are extracted from T1w and T2w scans. Subfield volumes of the hippocampus and amygdala can be extracted from a high-resolution T2w image.

  1 year

• Baseline microvascular pseudodiffusion

  Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.

  baseline

• Baseline microvascular perfusion fraction

  Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.

  baseline

• 1-Year microvascular pseudodiffusion

  Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.

  1 year

• 1-Year microvascular perfusion fraction

  Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.

  1 year

• Baseline white matter hyperintensity volumes

  The FLAIR scan attenuates the CSF signal and therefore, it is excellent in distinguishing white-matter abnormalities surrounding the CSF.

  baseline

• 1-Year white matter hyperintensity volumes

  The FLAIR scan attenuates the CSF signal and therefore, it is excellent in distinguishing white-matter abnormalities surrounding the CSF.

  1 year

• Baseline structural connectivity (DTI) fractional anisotropy

  This T2\*-weighted scan will measure the anatomical connections between brain areas.

  baseline

• Baseline structural connectivity (DTI) vessel density

  This T2\*-weighted scan will measure the anatomical connections between brain areas.

  baseline

• 1-Year structural connectivity (DTI) fractional anisotropy

  This T2\*-weighted scan will measure the anatomical connections between brain areas.

  1 year

• 1-Year structural connectivity (DTI) vessel density

  This T2\*-weighted scan will measure the anatomical connections between brain areas.

  1 year

• Baseline activity in regions involved in emotion processing

  Task-based fMRI will assess activity in, amongst others, the amygdala and anterior cingulate cortex. Activity is expressed in t-values between activity (average measured BOLD signal in region-of-interest) in two conditions/contrasts: Faces versus Rest Faces versus Shapes

  baseline

• 1-Year activity in regions involved in emotion processing

  Task-based fMRI will assess activity in, amongst others, the amygdala and anterior cingulate cortex. Activity is expressed in t-values between activity (average measured BOLD signal in region-of-interest) in two conditions/contrasts: Faces versus Rest Faces versus Shapes

  1 year

• Baseline functional connectivity and derivatives thereof

  Resting-state fMRI will assess functional connectivity between brain regions and networks. Derivations include e.g. directed or time varying functional connectivity.

  baseline

• 1-Year functional connectivity and derivatives thereof

  Resting-state fMRI will assess functional connectivity between brain regions and networks. Derivations include e.g. directed or time varying functional connectivity.

  1 year

• Baseline cerebral blood flow

  Arterial spin labeling measures blood flow from which cerebral blood flow can be extracted

  baseline

• 1-Year cerebral blood flow

  Arterial spin labeling measures blood flow from which cerebral blood flow can be extracted

  1 year

• Baseline total volume microbleeds (susceptibility-weighted imaging)

  This T2\*-weighted scan is used to detect brain microbleeds

  baseline

• Baseline total number of microbleeds (susceptibility-weighted imaging)

  This T2\*-weighted scan is used to detect brain microbleeds

  baseline

• 1-Year total volume microbleeds (susceptibility-weighted imaging)

  This T2\*-weighted scan is used to detect brain microbleeds

  1 year

• 1-Year total number of microbleeds (susceptibility-weighted imaging)

  This T2\*-weighted scan is used to detect brain microbleeds

  1 year

• Baseline depression severity score

  Full spectrum of symptoms assessed via the Hamilton Depression Rating Scale (HDRS) 17 questionnaire. 17 items are rated from 0-4 or 0-2. Total scores ranges from 0-51. The HDRS includes questions regarding symptoms such as: depressed mood, feelings of guilt, suicide, anxiety and more.

  baseline

• 3-Months depression severity score

  Full spectrum of symptoms assessed via the Hamilton Depression Rating Scale (HDRS) 17 questionnaire. 17 items are rated from 0-4 or 0-2. Total scores ranges from 0-51. The HDRS includes questions regarding symptoms such as: depressed mood, feelings of guilt, suicide, anxiety and more.

  3 months

• 6-Months depression severity score

  Full spectrum of symptoms assessed via the Hamilton Depression Rating Scale (HDRS) 17 questionnaire. 17 items are rated from 0-4 or 0-2. Total scores ranges from 0-51. The HDRS includes questions regarding symptoms such as: depressed mood, feelings of guilt, suicide, anxiety and more.

  6 months

• 9-Months depression severity score

  Full spectrum of symptoms assessed via the Hamilton Depression Rating Scale (HDRS) 17 questionnaire. 17 items are rated from 0-4 or 0-2. Total scores ranges from 0-51. The HDRS includes questions regarding symptoms such as: depressed mood, feelings of guilt, suicide, anxiety and more.

  9 months

• 1-Year depression severity score

  Full spectrum of symptoms assessed via the Hamilton Depression Rating Scale (HDRS) 17 questionnaire. 17 items are rated from 0-4 or 0-2. Total scores ranges from 0-51. The HDRS includes questions regarding symptoms such as: depressed mood, feelings of guilt, suicide, anxiety and more.

  1 year

• Baseline depression severity score

  Full spectrum of symptoms assessed via the Hamilton Depression Rating Scale (HDRS) 17 questionnaire. 17 items are rated from 0-4 or 0-2. Total scores ranges from 0-51. The HDRS includes questions regarding symptoms such as: depressed mood, feelings of guilt, suicide, anxiety and more.

  At baseline

Secondary Outcomes (10)

• Sleep score

  At baseline and after 1 year

• Anxiety score

  At baseline and after 1 year

• Neuroticism score

  At baseline and after 1 year

• Childhood trauma score

  At baseline and after 1 year

• Psychosis score

  At baseline and after 1 year

Study Arms (2)

MDD

Major depressive disorder patients (unipolar)

Device: MRI research

CON

(Control) non-depressed

Device: MRI research

Interventions

MRI research DEVICE

3T MRI protocol of \~1 hour

CON; MDD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

MMD versus (controls) non-depressed

You may qualify if:

• Satisfy DSM-5 clinical criteria for MDD (acute and subacute duration)
• Unipolar depression (i.e. no bipolar depression/mania)
• Age: 18-65 (m/f)
• Willing and able to provide informed consent and agree that incidental findings are reported

You may not qualify if:

• Concurrent neurological disorder (e.g. epilepsy, stroke, head trauma, etc.)
• Current substance or alcohol abuse
• History of psychosis, bipolar depression, autism spectrum disorder, attention deficit hyperactivity disorder or (mild) intellectual disability
• Contra-indication for MRI (see MRI safety form), includes implants, tattoos non-compatible with brain MRI, pregnancy, claustrophobia) Previous or current treatment with electroconvulsive therapy (ECT), deep-brain stimulation (DBS) or transcranial magnetic stimulation (TMS)
• More than 3 depressive episodes in the past
• healthy controls
• Age: 18-65 (m/f)
• Willing and able to provide informed consent and agree that incidental findings are reported
• A neurological disorder (e.g. epilepsy, stroke, head trauma, etc.)
• Current substance or alcohol abuse
• History of psychosis, bipolar depression, autism spectrum disorder, attention deficit and hyperactivity disorder or (mild) intellectual disability
• Contra-indication for MRI (see MRI safety form), includes implants, tattoos non-compatible with brain MRI, pregnancy, claustrophobia)
• Has a current episode of a MDD or ever had an MDD
• Previous or current treatment with electroconvulsive therapy (ECT), deep-brain stimulation (DBS) or transcranial magnetic stimulation (TMS)

Sponsors & Collaborators

• Eindhoven University of Technology: lead
• Clinical Trial Center Maastricht B.V.: collaborator

Study Sites (1)

Stichting Kempenhaeghe

Heeze, North Brabant, 5612 AZ, Netherlands

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2022
• First Posted: January 27, 2023
• Study Start: July 1, 2021
• Primary Completion: April 28, 2023
• Study Completion: April 28, 2023
• Last Updated: April 2, 2025

Record last verified: 2025-03

Locations

NL (1)