Depressive Disorder, MajorNEUROTRENDNCT05701267
Neuro MRI Biomarkers for Treatment Navigation in Depression
An observational study of Depressive Disorder, Major, run by Eindhoven University of Technology at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Depressive Disorder, Major
- What is being tested?
- MRI research
- Type of treatment
- Medical device
- How many people
- 83 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Jul 2021to 28 Apr 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: MMD versus (controls) non-depressed
Who may be able to join
- 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
- Age: 18-65 (m/f)
- Willing and able to provide informed consent and agree that incidental findings are reported
Who cannot join
- 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
- 60 healthy controls
Show all 12Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
Read the detailed description
Limitation to research to date
Heterogeneous findings of current studies may indicate that MDD has been approached too much as a homogeneous concept, whereas analysing subtypes might be more useful. The literature supports the existence of different MDD subtypes based on biological variables and/or clinical features. Research has distinguished 3 types of MDD based on depressive, symptomatology: a severe melancholic class, a severe atypical class and a class of moderate severity. Both depression severity (moderate vs severe) and the nature of depressive symptoms (melancholic vs atypical) were found to be important differentiators between those subtypes. Other subgroups of relevance may be remission vs. non-remission, early onset vs. late onset depression. The relation with neuroimaging findings is scarce and inconsistent. As depressive symptoms may also strongly fluctuate over time, repeated MRI and clinical data acquisition at different points in time is warranted. There is a relative scarcity of longitudinal MRI studies on MDD. Large representative samples are warranted, addressing multiple factors such as sociodemographic characteristics, clinical history (incl. childhood trauma), co-morbidity and monitoring of treatment, including type and duration. This will elucidate causative mechanisms as well as the role of treatment, which may pave the path towards diagnostic subtyping and treatment navigation. Moreover, brain alterations are usually described on a structural, functional and vascular level and seldom from an integral approach, let alone in a longitudinal design. A multi-modal approach whereby the three levels are considered might thus increase the reproducibility of findings. In addition, there is an urgent need to find biomarkers that are meaningful on the individual patient level. Machine learning is a technique that can be utilized to allow imaging risk markers to be identified at the level of subtypes and ultimately on the individual level, which is crucial for clinical applicability.
Current study
The Neurotrend study will contribute to the existing literature by aiming to predict outcome in MDD using multi-modal imaging with an observational study design. Two scanning sessions with one year in between will be held for patients with MDD and controls, as well as a broad assessment of clinical, cognitive and demographic variables (at baseline and 1-year follow-up). Predicting outcome at the level of subtypes/individuals in a naturalistic clinical setting is a different approach to identify biomarkers than most studies have done so far. For this purpose, machine learning will be used, which is a powerful method to identify biomarkers from the different MRI modalities. For the first time, IVIM and T2*-weighted imaging will be included in the MRI protocol to yield more insight into the microvascularity and microbleeds of the brain. In addition, other novel techniques will be applied to increase the chance of finding meaningful biomarkers. For instance, with respect to the brain alterations on a structural level, high spatial resolutions (using multiband imaging) and better automated segmentation methods will be used to examine the substructures of brain regions with high accuracy as substructural imaging is becoming more popular and could identify more reliable biomarkers. For the brain alterations on a functional level, multiband and multi-echo imaging lead to higher spatial/temporal resolution which will help to reduce the noise and artifacts to which fMRI is very susceptible.
- Conditions
- Depressive Disorder, Major
- Being tested
- MRI research
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI researchDevice
3T MRI protocol of ~1 hour
| Study group | Role | What they receive |
|---|---|---|
| MDD | Major depressive disorder patients (unipolar) Receives: Device: MRI research | |
| CON | (Control) non-depressed Receives: Device: MRI research |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 1 year
Baseline microvascular pseudodiffusion
Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.
Measured: baseline
Baseline microvascular perfusion fraction
Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.
Measured: baseline
1-Year microvascular pseudodiffusion
Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.
Measured: 1 year
1-Year microvascular perfusion fraction
Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.
Measured: 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.
Measured: 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.
Measured: 1 year
Baseline structural connectivity (DTI) fractional anisotropy
This T2*-weighted scan will measure the anatomical connections between brain areas.
Measured: baseline
Baseline structural connectivity (DTI) vessel density
This T2*-weighted scan will measure the anatomical connections between brain areas.
Measured: baseline
1-Year structural connectivity (DTI) fractional anisotropy
This T2*-weighted scan will measure the anatomical connections between brain areas.
Measured: 1 year
1-Year structural connectivity (DTI) vessel density
This T2*-weighted scan will measure the anatomical connections between brain areas.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 1 year
Baseline cerebral blood flow
Arterial spin labeling measures blood flow from which cerebral blood flow can be extracted
Measured: baseline
1-Year cerebral blood flow
Arterial spin labeling measures blood flow from which cerebral blood flow can be extracted
Measured: 1 year
Baseline total volume microbleeds (susceptibility-weighted imaging)
This T2*-weighted scan is used to detect brain microbleeds
Measured: baseline
Baseline total number of microbleeds (susceptibility-weighted imaging)
This T2*-weighted scan is used to detect brain microbleeds
Measured: baseline
1-Year total volume microbleeds (susceptibility-weighted imaging)
This T2*-weighted scan is used to detect brain microbleeds
Measured: 1 year
1-Year total number of microbleeds (susceptibility-weighted imaging)
This T2*-weighted scan is used to detect brain microbleeds
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At baseline
Secondary outcomes (10)
Sleep score
As assessed from the insomnia severity index questionnaire. 7 items are scored from 0-4. Range scores: 0-28. Higher score ---> More insomnia-related symptoms.
Measured: At baseline and after 1 year
Anxiety score
As assessed from the State-Trait Anxiety Inventory Dutch Y 1 (STAI-DY1) questionnaire. 20 items are scored from 1-5. Range scores: 20-100. Higher score --> More anxiety-related symptoms
Measured: At baseline and after 1 year
Neuroticism score
As assessed from the Neuroticism, Extraversion, Openness to Experiences Five-Factor Inventory (NEO-FFI) questionnaire. 60 items can be scored from 1-5. Range scores: 60-300. Higher scores ---> more symptoms related to neuroticism.
Measured: At baseline and after 1 year
Childhood trauma score
As assessed from the Childhood trauma questionnaire (Dutch: JTV) - long version. 28 items can be scored from 1-5. Range scores: 28-140. Higher score --> More traumatic experience during childhood.
Measured: At baseline and after 1 year
Psychosis score
As assessed from the Community Assessment of Psychic Experience (CAPE) questionnaire. 42 items range from 0-3. If an item is scored from 1-3, a more detailed question should be filled in ranging from 0-3. Range scores: 0-252 (42 * (3 * 2)). Higher scores --> more psychotic symptoms.
Measured: At baseline and after 1 year
Comorbidities
As assessed from the MINI neuropsychiatric interview. No scores/scale. Labels indicate different comorbidities that might be crucial for biological subtype identification.
Measured: At baseline and after 1 year
Medication and treatment
Custom questionnaire to assess type and dose of medication and types of treatments received. No scores and no scale.
Measured: Every 3 months for MDD - At baseline and 1 year follow-up for healthy controls
Psychomotor speed and reaction time
As assessed by an eye-tracker camera and custom task in Tobii software Subjects have to focus on a white block appearing multiple times on a black background. It is an indication of medication influence on cognition. No scale; faster reaction times indicate higher performance.
Measured: At baseline and after 1 year
Attention and processing speed
As assessed by FEPSY software. Includes visual reaction times and pattern recognition tasks. No scale; faster reaction times indicate higher performance.
Measured: At baseline and after 1 year
Long and short-term verbal memory
As assessed by the RVALT (15 words memory and recall test). Each repetition a score from 1-15 can be achieved; higher scores indicate higher performance.
Measured: At baseline and after 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2023
- Study start1 Jul 2021
- Primary completion28 Apr 2023
- Study completion28 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depressive Disorder, MajorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eindhoven University of Technology
- Sponsor type
- University, hospital or other
- Collaborators
- Clinical Trial Center Maastricht B.V.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05701267
- Sponsor's protocol ID
- Neurotrend_001
- Acronym
- NEUROTREND
- Status last verified
- Mar 2025
- First submitted
- 22 Feb 2022
- Last updated
- 2 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: No plan available yet
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuro MRI Biomarkers for Treatment Navigation in Depression
- ClinicalTrials.gov ID
- NCT05701267
- Acronym / sponsor ID
- NEUROTREND / Neurotrend_001
- Conditions
- Depressive Disorder, Major
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Eindhoven University of TechnologyUniversity, hospital or other
- Collaborators
- Clinical Trial Center Maastricht B.V.
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 28 Apr 2023 (actual)
- Study completion
- 28 Apr 2023 (actual)
- First posted
- 27 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Limitation to research to date
Heterogeneous findings of current studies may indicate that MDD has been approached too much as a homogeneous concept, whereas analysing subtypes might be more useful. The literature supports the existence of different MDD subtypes based on biological variables and/or clinical features. Research has distinguished 3 types of MDD based on depressive, symptomatology: a severe melancholic class, a severe atypical class and a class of moderate severity. Both depression severity (moderate vs severe) and the nature of depressive symptoms (melancholic vs atypical) were found to be important differentiators between those subtypes. Other subgroups of relevance may be remission vs. non-remission, early onset vs. late onset depression. The relation with neuroimaging findings is scarce and inconsistent. As depressive symptoms may also strongly fluctuate over time, repeated MRI and clinical data acquisition at different points in time is warranted. There is a relative scarcity of longitudinal MRI studies on MDD. Large representative samples are warranted, addressing multiple factors such as sociodemographic characteristics, clinical history (incl. childhood trauma), co-morbidity and monitoring of treatment, including type and duration. This will elucidate causative mechanisms as well as the role of treatment, which may pave the path towards diagnostic subtyping and treatment navigation. Moreover, brain alterations are usually described on a structural, functional and vascular level and seldom from an integral approach, let alone in a longitudinal design. A multi-modal approach whereby the three levels are considered might thus increase the reproducibility of findings. In addition, there is an urgent need to find biomarkers that are meaningful on the individual patient level. Machine learning is a technique that can be utilized to allow imaging risk markers to be identified at the level of subtypes and ultimately on the individual level, which is crucial for clinical applicability.
Current study
The Neurotrend study will contribute to the existing literature by aiming to predict outcome in MDD using multi-modal imaging with an observational study design. Two scanning sessions with one year in between will be held for patients with MDD and controls, as well as a broad assessment of clinical, cognitive and demographic variables (at baseline and 1-year follow-up). Predicting outcome at the level of subtypes/individuals in a naturalistic clinical setting is a different approach to identify biomarkers than most studies have done so far. For this purpose, machine learning will be used, which is a powerful method to identify biomarkers from the different MRI modalities. For the first time, IVIM and T2*-weighted imaging will be included in the MRI protocol to yield more insight into the microvascularity and microbleeds of the brain. In addition, other novel techniques will be applied to increase the chance of finding meaningful biomarkers. For instance, with respect to the brain alterations on a structural level, high spatial resolutions (using multiband imaging) and better automated segmentation methods will be used to examine the substructures of brain regions with high accuracy as substructural imaging is becoming more popular and could identify more reliable biomarkers. For the brain alterations on a functional level, multiband and multi-echo imaging lead to higher spatial/temporal resolution which will help to reduce the noise and artifacts to which fMRI is very susceptible.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MDD | – | Device: MRI researchMajor depressive disorder patients (unipolar) |
| CON | – | Device: MRI research(Control) non-depressed |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- MMD versus (controls) non-depressed
Key inclusion criteria (6 listed)
- 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
- Age: 18-65 (m/f)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRI research3T MRI protocol of ~1 hour | Device | CON, MDD |
Primary outcome
Basline brain region (subfield) volumes
Time frame: baseline
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 brain region (subfield) volumes
Time frame: 1 year
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 microvascular pseudodiffusion
Time frame: baseline
Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.
Baseline microvascular perfusion fraction
Time frame: baseline
Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.
1-Year microvascular pseudodiffusion
Time frame: 1 year
Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.
1-Year microvascular perfusion fraction
Time frame: 1 year
Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.
Baseline white matter hyperintensity volumes
Time frame: baseline
The FLAIR scan attenuates the CSF signal and therefore, it is excellent in distinguishing white-matter abnormalities surrounding the CSF.
1-Year white matter hyperintensity volumes
Time frame: 1 year
The FLAIR scan attenuates the CSF signal and therefore, it is excellent in distinguishing white-matter abnormalities surrounding the CSF.
Baseline structural connectivity (DTI) fractional anisotropy
Time frame: baseline
This T2*-weighted scan will measure the anatomical connections between brain areas.
Baseline structural connectivity (DTI) vessel density
Time frame: baseline
This T2*-weighted scan will measure the anatomical connections between brain areas.
1-Year structural connectivity (DTI) fractional anisotropy
Time frame: 1 year
This T2*-weighted scan will measure the anatomical connections between brain areas.
1-Year structural connectivity (DTI) vessel density
Time frame: 1 year
This T2*-weighted scan will measure the anatomical connections between brain areas.
Baseline activity in regions involved in emotion processing
Time frame: baseline
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 activity in regions involved in emotion processing
Time frame: 1 year
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 functional connectivity and derivatives thereof
Time frame: baseline
Resting-state fMRI will assess functional connectivity between brain regions and networks. Derivations include e.g. directed or time varying functional connectivity.
1-Year functional connectivity and derivatives thereof
Time frame: 1 year
Resting-state fMRI will assess functional connectivity between brain regions and networks. Derivations include e.g. directed or time varying functional connectivity.
Baseline cerebral blood flow
Time frame: baseline
Arterial spin labeling measures blood flow from which cerebral blood flow can be extracted
1-Year cerebral blood flow
Time frame: 1 year
Arterial spin labeling measures blood flow from which cerebral blood flow can be extracted
Baseline total volume microbleeds (susceptibility-weighted imaging)
Time frame: baseline
This T2*-weighted scan is used to detect brain microbleeds
Baseline total number of microbleeds (susceptibility-weighted imaging)
Time frame: baseline
This T2*-weighted scan is used to detect brain microbleeds
1-Year total volume microbleeds (susceptibility-weighted imaging)
Time frame: 1 year
This T2*-weighted scan is used to detect brain microbleeds
1-Year total number of microbleeds (susceptibility-weighted imaging)
Time frame: 1 year
This T2*-weighted scan is used to detect brain microbleeds
Baseline depression severity score
Time frame: baseline
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 depression severity score
Time frame: 3 months
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 depression severity score
Time frame: 6 months
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 depression severity score
Time frame: 9 months
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 depression severity score
Time frame: 1 year
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 depression severity score
Time frame: At baseline
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.
10 secondary outcomes
Sleep score
Time frame: At baseline and after 1 year
Anxiety score
Time frame: At baseline and after 1 year
Neuroticism score
Time frame: At baseline and after 1 year
Childhood trauma score
Time frame: At baseline and after 1 year
Psychosis score
Time frame: At baseline and after 1 year
Comorbidities
Time frame: At baseline and after 1 year
Medication and treatment
Time frame: Every 3 months for MDD - At baseline and 1 year follow-up for healthy controls
Psychomotor speed and reaction time
Time frame: At baseline and after 1 year
Attention and processing speed
Time frame: At baseline and after 1 year
Long and short-term verbal memory
Time frame: At baseline and after 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2025.
- Individual participant dataSharing planned: Undecided. No plan available yet
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Depressive Disorder, Major, run by Eindhoven University of Technology at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Basline brain region (subfield) volumes (time frame: baseline). The study lists 28 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2025.