Major Depressive DisorderNCT06203015
The Relations Among Endotoxin, Inflammatory Cytokines, Cognitive Markers and Brain MRI Changes in Subjects With Depressive Disorder
An observational study of Major Depressive Disorder and Inflammation, run by Lithuanian University of Health Sciences at 2 sites in Lithuania.
Trial summary
Major depressive disorder (MDD) is a chronic mental illness, with 60% lifetime risk of recurrence after the first MDD episode. Despite available treatment options for MDD, only about half to two-thirds of patients respond to first-line antidepressant treatment, and only 30% to 45% of patients achieve remission. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder, Inflammation, Cognitive Dysfunction
- What is being tested?
- The Cambridge Neuropsychological Test Automated Battery., Venous blood samples and brain MRI
- How many people
- 150 participants
- Where
- 2 sitesLithuania
- Study dates
- 1 Jun 2022to 1 Jun 2024
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study is being conducted at the hospital of the Lithuanian University of Health Sciences Kaunas Clinics Psychiatry Clinic (inpatient department), and the Nervous System Diseases Outpatient Department.
Who may be able to join
- ≥18 years old
- signed informed consent
- patients diagnosed with MDD (according to the WHO's [2019] International Classification of Diseases and related health problems categorization of mental disorders) for MDD group.
Who cannot join
- diagnosis of other mental disorders during the past one-year period (for MDD group).
- diagnosis of any mental disorders within the past one-year period, previous suicide attempt, or current suicide risk identified in the study (for control group).
- diagnosis of somatic diseases that may affect changes in inflammatory factors in the body (for both groups)
Trial locations and contacts
2 sites in 1 country.
Lithuania2 sites, 2 recruiting
- Recruiting
Psychiatry Department, Hospital of Lithuanian University of Health Sciences Kaunas Clinics
Kaunas, 50161
Egle Milasauskiene, MD, +37063458861, egle.milasauskiene@lsmu.lt
- Recruiting
Psychiatry Department, Hospital of Lithuanian University of Health Sciences Kaunas Clinics
Kaunas
Egle Milasauskiene, MD, egle.milasauskiene@lsmu.lt
About this study
Major depressive disorder (MDD) is a chronic mental illness, with 60% lifetime risk of recurrence after the first MDD episode. Despite available treatment options for MDD, only about half to two-thirds of patients respond to first-line antidepressant treatment, and only 30% to 45% of patients achieve remission. Scholars assume that this low remission rate and high rate of treatment resistance are due to the polyetiological nature of the disease, the heterogeneity of the clinical picture of depression, and the lack of biomarkers to stratify MDD subtypes. The aetiology of MDD, although researched extensively, remains unclear. None of the known mechanisms alone explains the pathogenesis of depression, meaning that the interplay of several factors contributes to the development of MDD. Accumulated scientific evidence has supported the importance of the immune system in the etiopathogenesis of MDD. Until now, the cause of the low-grade inflammation observed in this subgroup of MDD patients has been unclear. In the proposed study, the investigators will test a new hypothesis of the immune theory of the development of MDD: the endotoxin hypothesis of neurodegeneration. This hypothesis states that endotoxin, causes or contributes to neurodegeneration. Blood plasma levels of LPS are normally low but are elevated during infections, gut inflammation, gum disease, and neurodegenerative diseases. Dysbiosis may promote increased intestinal permeability ("leaky gut"), which leads to bacterial translocation across the intestinal barrier and into the circulation, thus forming of LPS and LPS-binding protein complex, which triggers the secretion of cytokines. Data suggest that LPS-induced peripheral inflammation can activate neuroinflammation. However, it is not known whether a low-level persistent presence of LPS in the circulatory system can cause low-grade chronic neuroinflammation leading to neurodegeneration and/or symptoms of MDD. Based on existing preclinical and clinical research data, the investigators hypothesise that an increase in blood plasma endotoxin and peripheral cytokines induce BBB dysfunction, neuroinflammation and neurodegenerative processes in specific etiologically relevant structures of the brain and cause clinical manifestation of depressive symptoms and cognitive damage. In this study the investigators are also going to investigate the effects of single nucleotide polymorphisms of four genes in relation to blood plasma endotoxin and peripheral cytokines concentrations and clinical manifestation of MDD.
- Conditions
- Major Depressive Disorder, Inflammation, Cognitive Dysfunction, Endotoxemia, Genetic Predisposition to Disease, Blood Brain Barrier Defect
- Being tested
- The Cambridge Neuropsychological Test Automated Battery., Venous blood samples, brain MRI, the Montgomery-Åsberg Depression Rating Scale, questionnaire prepared by the researchers
- Keywords
- Major depressive disorder, Inflammation, Endotoxin, Cognitive dysfunction, Genetic polymorphisms, Multiparametric Magnetic Resonance Imaging, Blood Brain Barrier
- Medical subject headings
- Depressive Disorder, Major, Inflammation, Cognitive Dysfunction, Endotoxemia, Genetic Predisposition to Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The Cambridge Neuropsychological Test Automated Battery.Diagnostic test
to determine cognitive dysfunction
Venous blood samplesDiagnostic test
to measure levels of cytokines, endotoxin, and genetic markers.
brain MRIDiagnostic test
to evaluate BBB permeability to water, brain structure volumes, white matter integrity, cerebral perfusion, and neurometabolite concentrations
the Montgomery-Åsberg Depression Rating ScaleDiagnostic test
to measure severity of depressive symptoms
questionnaire prepared by the researchersOther
collecting sociodemographic data and information about smoking status, BMI, data on the course of MDD, past treatment, comorbid diseases, and current use of medications.
| Study group | Role | What they receive |
|---|---|---|
| MDD patients | patients diagnosed with MDD (according to the WHO's [2019] International Classification of Diseases and related health problems categorization of mental disorders), diagnosed by a psychiatrist; ≥18 years old Receives: Diagnostic Test: The Cambridge Neuropsychological Test Automated Battery.; Diagnostic Test: Venous blood samples; Diagnostic Test: brain MRI; Diagnostic Test: the Montgomery-Åsberg Depression Rating Scale; Other: questionnaire prepared by the researchers | |
| Control group | Subjects who have not been diagnosed with any mental disorder in the past year; ≥18 years old Receives: Diagnostic Test: The Cambridge Neuropsychological Test Automated Battery.; Diagnostic Test: Venous blood samples; Diagnostic Test: brain MRI; Diagnostic Test: the Montgomery-Åsberg Depression Rating Scale; Other: questionnaire prepared by the researchers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Levels of blood plasma endotoxin and inflammatory cytokines between groups.
To evaluate the concentrations of blood plasma endotoxin and inflammatory cytokines among patients with MDD and in a control group. We hypothesize that an increase in blood plasma endotoxin is associated with an increase in blood inflammatory cytokines in the group of patients with MDD.
Measured: Day 1
Severity and manifestation of depressive symptoms.
Evaluate the severity and manifestation of different depressive symptoms. We hypothesize that endotoxin and inflammatory markers are associated with specific symptoms of MDD, allowing us to identify MDD patients with a specific LPS-induced/stimulated inflammatory depression subtype.
Measured: Day 1
Secondary outcomes (4)
Brain MRI
Perform a multiparametric brain MRI assessment of depressed patients and a control group. We hypothesize that, among patients with MDD, there are changes in blood-brain barrier permeability to water, levels of neuroinflammation and perfusion, and structural neurodegenerative changes that are associated with blood plasma endotoxin and cytokine concentrations.
Measured: Day 1
Cognitive dysfunction
Evaluate cognitive functions. We hypothesize that low-grade neuroinflammation negatively affects cognitive performance among patients with MDD.
Measured: Day 1
Covariates
Perform a subgroup analysis on neuroinflammation markers based on individuals' BMI and smoking status.
Measured: Day 1
Genetic markers
Determine possible genetic markers among MDD subjects in relation to blood plasma endotoxin and inflammatory cytokines concentrations that could predict a genetic predisposition to neuroinflammation, neurodegeneration and the development of MDD.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2024
- Study start1 Jun 2022
- Primary completion1 Jun 2024 (estimated)
- Study completion1 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies 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
- Cross-sectional
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lithuanian University of Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vesta Steibliene, Lithuanian University of Health Sciences
- Investigators
- Vesta Steibliene, PhD, MD, Principal investigator, Proffesor, Lithuanian University of Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06203015
- Sponsor's protocol ID
- DEPRINFLAMATION-Versija 3
- Status last verified
- Jan 2024
- First submitted
- 2 Jan 2024
- Last updated
- 12 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Milasauskiene E, Burkauskas J, Jesmanas S, Gleizniene R, Borutaite V, Skemiene K, Vaitkiene P, Adomaitiene V, Lukosevicius S, Gradauskiene B, Brown G, Steibliene V. The links between neuroinflammation, brain structure and depressive disorder: A cross-sectional study protocol. PLoS One. 2024 Nov 20;19(11):e0311218. doi: 10.1371/journal.pone.0311218. eCollection 2024.
PubMed 39565757
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Relations Among Endotoxin, Inflammatory Cytokines, Cognitive Markers and Brain MRI Changes in Subjects With Depressive Disorder
- ClinicalTrials.gov ID
- NCT06203015
- Acronym / sponsor ID
- DEPRINFLAMATION-Versija 3
- Conditions
- Major Depressive Disorder, Inflammation, Cognitive Dysfunction, Endotoxemia, Genetic Predisposition to Disease, Blood Brain Barrier Defect
- Keywords
- Major depressive disorder, Inflammation, Endotoxin, Cognitive dysfunction, Genetic polymorphisms, Multiparametric Magnetic Resonance Imaging, Blood Brain Barrier
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Lithuanian University of Health SciencesUniversity, hospital or other
- Study start
- 1 Jun 2022 (actual)
- Primary completion
- 1 Jun 2024 (estimated)
- Study completion
- 1 Jun 2024 (estimated)
- First posted
- 12 Jan 2024 (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.
Major depressive disorder (MDD) is a chronic mental illness, with 60% lifetime risk of recurrence after the first MDD episode. Despite available treatment options for MDD, only about half to two-thirds of patients respond to first-line antidepressant treatment, and only 30% to 45% of patients achieve remission. Scholars assume that this low remission rate and high rate of treatment resistance are due to the polyetiological nature of the disease, the heterogeneity of the clinical picture of depression, and the lack of biomarkers to stratify MDD subtypes. The aetiology of MDD, although researched extensively, remains unclear. None of the known mechanisms alone explains the pathogenesis of depression, meaning that the interplay of several factors contributes to the development of MDD. Accumulated scientific evidence has supported the importance of the immune system in the etiopathogenesis of MDD. Until now, the cause of the low-grade inflammation observed in this subgroup of MDD patients has been unclear. In the proposed study, the investigators will test a new hypothesis of the immune theory of the development of MDD: the endotoxin hypothesis of neurodegeneration. This hypothesis states that endotoxin, causes or contributes to neurodegeneration. Blood plasma levels of LPS are normally low but are elevated during infections, gut inflammation, gum disease, and neurodegenerative diseases. Dysbiosis may promote increased intestinal permeability ("leaky gut"), which leads to bacterial translocation across the intestinal barrier and into the circulation, thus forming of LPS and LPS-binding protein complex, which triggers the secretion of cytokines. Data suggest that LPS-induced peripheral inflammation can activate neuroinflammation. However, it is not known whether a low-level persistent presence of LPS in the circulatory system can cause low-grade chronic neuroinflammation leading to neurodegeneration and/or symptoms of MDD. Based on existing preclinical and clinical research data, the investigators hypothesise that an increase in blood plasma endotoxin and peripheral cytokines induce BBB dysfunction, neuroinflammation and neurodegenerative processes in specific etiologically relevant structures of the brain and cause clinical manifestation of depressive symptoms and cognitive damage. In this study the investigators are also going to investigate the effects of single nucleotide polymorphisms of four genes in relation to blood plasma endotoxin and peripheral cytokines concentrations and clinical manifestation of MDD.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MDD patients | – | Diagnostic Test: The Cambridge Neuropsychological Test Automated Battery., Diagnostic Test: Venous blood samples, Diagnostic Test: brain MRI, Diagnostic Test: the Montgomery-Åsberg Depression Rating Scale, Other: questionnaire prepared by the researcherspatients diagnosed with MDD (according to the WHO's [2019] International Classification of Diseases and related health problems categorization of mental disorders), diagnosed by a psychiatrist; ≥18 years old |
| Control group | – | Diagnostic Test: The Cambridge Neuropsychological Test Automated Battery., Diagnostic Test: Venous blood samples, Diagnostic Test: brain MRI, Diagnostic Test: the Montgomery-Åsberg Depression Rating Scale, Other: questionnaire prepared by the researchersSubjects who have not been diagnosed with any mental disorder in the past year; ≥18 years old |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study is being conducted at the hospital of the Lithuanian University of Health Sciences Kaunas Clinics Psychiatry Clinic (inpatient department), and the Nervous System Diseases Outpatient Department.
Key inclusion criteria (3 listed)
- ≥18 years old
- signed informed consent
- patients diagnosed with MDD (according to the WHO's [2019] International Classification of Diseases and related health problems categorization of mental disorders) for MDD group.
Key exclusion criteria (3 listed)
- diagnosis of other mental disorders during the past one-year period (for MDD group).
- diagnosis of any mental disorders within the past one-year period, previous suicide attempt, or current suicide risk identified in the study (for control group).
- diagnosis of somatic diseases that may affect changes in inflammatory factors in the body (for both groups)
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 |
|---|---|---|
| The Cambridge Neuropsychological Test Automated Battery.to determine cognitive dysfunction | Diagnostic test | Control group, MDD patients |
| Venous blood samplesto measure levels of cytokines, endotoxin, and genetic markers. | Diagnostic test | Control group, MDD patients |
| brain MRIto evaluate BBB permeability to water, brain structure volumes, white matter integrity, cerebral perfusion, and neurometabolite concentrations | Diagnostic test | Control group, MDD patients |
| the Montgomery-Åsberg Depression Rating Scaleto measure severity of depressive symptoms | Diagnostic test | Control group, MDD patients |
| questionnaire prepared by the researcherscollecting sociodemographic data and information about smoking status, BMI, data on the course of MDD, past treatment, comorbid diseases, and current use of medications. | Other | Control group, MDD patients |
Primary outcome
Levels of blood plasma endotoxin and inflammatory cytokines between groups.
Time frame: Day 1
To evaluate the concentrations of blood plasma endotoxin and inflammatory cytokines among patients with MDD and in a control group. We hypothesize that an increase in blood plasma endotoxin is associated with an increase in blood inflammatory cytokines in the group of patients with MDD.
Severity and manifestation of depressive symptoms.
Time frame: Day 1
Evaluate the severity and manifestation of different depressive symptoms. We hypothesize that endotoxin and inflammatory markers are associated with specific symptoms of MDD, allowing us to identify MDD patients with a specific LPS-induced/stimulated inflammatory depression subtype.
4 secondary outcomes
Brain MRI
Time frame: Day 1
Cognitive dysfunction
Time frame: Day 1
Covariates
Time frame: Day 1
Genetic markers
Time frame: Day 1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2024.
- Derived from this study: PubMed 39565757Milasauskiene E, Burkauskas J, Jesmanas S, Gleizniene R, Borutaite V, Skemiene K, Vaitkiene P, Adomaitiene V, Lukosevicius S, Gradauskiene B, Brown G, Steibliene V. The links between neuroinflammation, brain structure and depressive disorder: A cross-sectional study protocol. PLoS One. 2024 Nov 20;19(11):e0311218. doi: 10.1371/journal.pone.0311218. eCollection 2024.
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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.
Vesta Steibliene, PhD, MD principal investigator
Proffesor, Lithuanian University of Health Sciences
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Major Depressive Disorder and Inflammation, run by Lithuanian University of Health Sciences at 2 sites in Lithuania.
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 3 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 12 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Lithuania. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Egle Milasauskiene, MD (+37063458861, egle.milasauskiene@lsmu.lt), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Levels of blood plasma endotoxin and inflammatory cytokines between groups. (time frame: Day 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06203015, which also lists 1 linked publication.
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 12 Jan 2024.