Treatment Resistant DepressionNCT04021823
Neurobiological Analyses Within the FORESEE III Study
An observational study of Treatment Resistant Depression, run by University Hospital Freiburg at 1 site in Germany.
Trial summary
In this observational, non-invasive clinical study different neurobiological analyses will be performed in a group of patients with severe treatment resistant major depression participating in an efficacy study of deep brain stimulation of the superolateral branch of the medial forebrain bundle (slMFB) - FORESEE III. Read more about this study
- Who is it for?
- Ages 20 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Treatment Resistant Depression
- How many people
- 50 participants
- Where
- 1 siteGermany
- Study dates
- 1 Aug 2019to Jun 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 20 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Eligible participants are patients who participate in the FORESEE III study (NCT03653858) and have provided written informed consent to take part in this additional observational study. All patients suffering from severe, treatment-resistant depression, i.e. patients who have not sufficiently improved under established antidepressant therapies (such as psychotherapy, antidepressant drug therapy, and electroconvulsive therapy). As well as age- and sex-matched healthy controls.
Who may be able to join
- All enrolled subjects of the Controlled Randomized Clinical Trial to assess Efficacy of Deep Brain Stimulation (DBS) of the slMFB in Patients with Treatment Resistant Major Depression (FORESEE III) may participate in this study.
- All healthy volunteers without any clinically significant psychiatric or somatic symptoms are eligible.
Who cannot join
- Non-Caucasian (because of requirements for genetic/epigenetic analyses)
- Somatic diseases like diabetes, cancer and severe liver- and kidney-diseases
- Healthy Controls:
- Any clinically significant psychiatric symptoms
- Conditions like diabetes, cancer or severe liver- and kidney diseases
- Drug or alcohol abuse
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University Hospital Freiburg
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Susanne Spanier, 0049 761 270 69800, susanne.spanier@uniklinik-freiburg.de
Thomas E. Schläpfer, Prof. Dr., 0049 761 270 68820, thomas.schlaepfer@uniklinik-freiburg.de
About this study
In this observational, non-invasive clinical study different neurobiological analyses will be performed in a group of patients with severe treatment resistant major depression participating in an efficacy study of deep brain stimulation of the superolateral branch of the medial forebrain bundle (slMFB) - FORESEE III.
Read the detailed description
This study is a sub-project of the FORESEE III study (Controlled Randomized Clinical Trial to assess Efficacy of Deep Brain Stimulation (DBS) of the slMFB in Patients with Treatment Resistant Major Depression). The FORESEE III study itself is a randomized, sham-controlled, double blind (patient and observer blinded) clinical trial to assess the antidepressant effect of DBS compared to sham.
The aim of this sub-project is to analyze the time-course of biological correlates of treatment resistant major depression as well as neurobiological markers of treatment response to treatment with DBS in a well-characterized patient population during 12 month of DBS.
Specific neurobiological analyses include testing of
- epigenetic markers (DNA methylation in candidate genes of depression and epigenome-wide association studies, EWAS)
- markers of neuroinflammation (cytokines, neuropeptides and other immune factors)
- micro RNAs and transcriptome signatures
- markers of neurodegeneration (neurofilament light protein)
- metabolomic analyses and
- endocrinological parameters including glucose tolerance.
All markers will be tested in blood samples (and urine samples for metaboloic profiling) before neurosurgery as well as at several time points during DBS and sham condition intervals.
Additionally hemodynamic parameters will be analysed at test stimulation of the slMFB during neurosurgery.
The results will be correlated with clinical and other biological response parameters of the FORESEE III study and are hypothesized to indicate treatment response as well as allowing prediction of response to DBS. All neurobiological analyses will be linked in a tightly integrated and comprehensive translational approach.
Further, a volunteer group of healthy controls will be recruited and tested for blood-markers of neurodegeneration (neurofilament light protein, 4.) as well as metabolomic analyses in blood and urine (5.).
- Conditions
- Treatment Resistant Depression
- Keywords
- Treatment Resistant Depression, Neurobiological correlates of treatment resistant depression, Predictors of treatment response in DBS
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| DBS patients | Patients with treatment resistant major depression participating in the FORESEE III study. | |
| Healthy controls | Age- and sex-matched healthy controls undergoing analyses of neurodegenerative markers (neurofilament light protein) in blood and metabolomic analyses in blood and urine. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in DNA methylation patterns in plasma at 1 month of deep brain stimulation (DBS)
Epigenetic mechanisms such as DNA methylation crucially govern gene function and have been shown to be temporally dynamic and responsive to environmental stress. Epigenetic patterns in blood, saliva or other peripheral material have been suggested to partly reflect central epigenetic processes.
DNA will by isolated and undergo bisulfite conversion. Using pyro- and direct sequencing, samples will be analyzed for DNA methylation in candidate genes of depression.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 1 month of DBS (week 5 group A, week 21 group B)
Change from baseline in DNA methylation patterns in plasma at 4 month of deep brain stimulation (DBS)
Epigenetic mechanisms such as DNA methylation crucially govern gene function and have been shown to be temporally dynamic and responsive to environmental stress. Epigenetic patterns in blood, saliva or other peripheral material have been suggested to partly reflect central epigenetic processes.
DNA will by isolated and undergo bisulfite conversion. Using pyro- and direct sequencing, samples will be analyzed for DNA methylation in candidate genes of depression.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 4 month of DBS (week 17 group A, week 33 group B)
Change from baseline in DNA methylation patterns in plasma at 12 month of deep brain stimulation (DBS)
Epigenetic mechanisms such as DNA methylation crucially govern gene function and have been shown to be temporally dynamic and responsive to environmental stress. Epigenetic patterns in blood, saliva or other peripheral material have been suggested to partly reflect central epigenetic processes.
DNA will by isolated and undergo bisulfite conversion. Using pyro- and direct sequencing, samples will be analyzed for DNA methylation in candidate genes of depression.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 12 month of DBS (end of study both groups)
Change from baseline in neuroinflammatory and neuropeptide patterns at 1 month of deep brain stimulation (DBS)
A new method of analysis (Proseek® Multiplex Inflammation, Olink Bioscience, Uppsala, Sweden) will be used to determine any change in patterns of relevant neuropeptides and inflammatory markers. This multiplex proximity extension assay (PEA) will simultaneously analyze 92 different proteins, including cytokines, neuropeptides and other immune factors.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 1 month of DBS (week 5 group A, week 21 group B)
Change from baseline in neuroinflammatory and neuropeptide patterns at 4 month of deep brain stimulation (DBS)
A new method of analysis (Proseek® Multiplex Inflammation, Olink Bioscience, Uppsala, Sweden) will be used to determine any change in patterns of relevant neuropeptides and inflammatory markers. This multiplex proximity extension assay (PEA) will simultaneously analyze 92 different proteins, including cytokines, neuropeptides and other immune factors.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 4 month of DBS (week 17 group A, week 33 group B)
Change from baseline in neuroinflammatory and neuropeptide patterns at 12 month of deep brain stimulation (DBS)
A new method of analysis (Proseek® Multiplex Inflammation, Olink Bioscience, Uppsala, Sweden) will be used to determine any change in patterns of relevant neuropeptides and inflammatory markers. This multiplex proximity extension assay (PEA) will simultaneously analyze 92 different proteins, including cytokines, neuropeptides and other immune factors.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 12 month of DBS (end of study both groups)
Change from baseline in transcriptome profiles at 1 month of deep brain stimulation (DBS)
A massive parallel next generation deep sequencing (NGS) technology will be used followed by bioinformatic network analysis to determine intraindividual changes in exosomal miR ( (miRs, 19-22 nt long non-coding RNAs) and transcriptome profiles.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 1 month of DBS (week 5 group A, week 21 group B)
Change from baseline in exosomal Micro-RNA (miR) expression levels and transcriptome profiles at 4 month of deep brain stimulation (DBS)
A massive parallel next generation deep sequencing (NGS) technology will be used followed by bioinformatic network analysis to determine intraindividual changes in exosomal miR ( (miRs, 19-22 nt long non-coding RNAs) and transcriptome profiles.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 4 month of DBS (week 17 group A, week 33 group B)
Change from baseline in exosomal Micro-RNA (miR) expression levels and transcriptome profiles at 12 month of deep brain stimulation (DBS)
A massive parallel next generation deep sequencing (NGS) technology will be used followed by bioinformatic network analysis to determine intraindividual changes in exosomal miR ( (miRs, 19-22 nt long non-coding RNAs) and transcriptome profiles.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 12 month of DBS (end of study both groups)
Change from baseline in plasma levels of Neurofilament light protein at 2 days before surgical device implantation
Neurofilament light protein is part of the neuroaxonal cytoskeleton and can be released into plasma following neuroaxonal damage. In plasma it will be measured by single-molecule array (SiMoA) assays.
Measured: At baseline (up to 10 to 7 weeks before surgical device implantation) and at 2 days before surgical device implantation
Change from baseline in plasma levels of Neurofilament light protein at 1 month of deep brain stimulation (DBS)
Neurofilament light protein is part of the neuroaxonal cytoskeleton and can be released into plasma following neuroaxonal damage. In plasma it will be measured by single-molecule array (SiMoA) assays.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 1 month of DBS (week 5 group A, week 21 group B)
Change from baseline in plasma levels of Neurofilament light protein at 4 month of deep brain stimulation (DBS)
Neurofilament light protein is part of the neuroaxonal cytoskeleton and can be released into plasma following neuroaxonal damage. In plasma it will be measured by single-molecule array (SiMoA) assays.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 4 month of DBS (week 17 group A, week 33 group B)
Change from baseline in plasma levels of Neurofilament light protein at 12 month of deep brain stimulation (DBS)
Neurofilament light protein is part of the neuroaxonal cytoskeleton and can be released into plasma following neuroaxonal damage. In plasma it will be measured by single-molecule array (SiMoA) assays.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 12 month of DBS (end of study both groups)
Change from baseline in metabolite profiles in plasma and urine at 1 month of deep brain stimulation (DBS)
Metabolite profiles of plasma and urine samples will be analysed by chromatographic separation techniques, different mass spectrometric ionization modes and mass analyzers in order to assess molecular changes in the metabolome. The metabolomic methodologies may include fingerprinting, nontargeted, and targeted approaches, metabolic profiling and metabolic flux analysis.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 1 month of DBS (week 5 group A, week 21 group B)
Change from baseline in metabolite profiles in plasma and urine at 4 month of deep brain stimulation (DBS)
Metabolite profiles of plasma and urine samples will be analysed by chromatographic separation techniques, different mass spectrometric ionization modes and mass analyzers in order to assess molecular changes in the metabolome. The metabolomic methodologies may include fingerprinting, nontargeted, and targeted approaches, metabolic profiling and metabolic flux analysis.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 4 month of DBS (week 17 group A, week 33 group B)
Change from baseline in metabolite profiles in plasma and urine at 12 month of deep brain stimulation (DBS)
Metabolite profiles of plasma and urine samples will be analysed by chromatographic separation techniques, different mass spectrometric ionization modes and mass analyzers in order to assess molecular changes in the metabolome. The metabolomic methodologies may include fingerprinting, nontargeted, and targeted approaches, metabolic profiling and metabolic flux analysis.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at 12 month of DBS (end of study both groups)
Change from baseline in insuline resistance at week 41
An oral glucose tolerance test with blood measures of glucose, insulin and c-peptide at several time points during a period of 3 hours after oral intake of 75g glucose will be performed.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at week 41 (both groups)
Change from baseline in systemic metabolic parameters at week 41
Different systemic metabolic parameters will be measured in blood.
Measured: At baseline (up to 10 weeks before surgical device implantation) and at week 41 (both groups)
Cardiac stroke volume (ml)
Measured with ClearSight System, Edwards Lifesciences (allowing non-invasive and real-time continuous hemodynamic monitoring).
Measured: At test stimulation of the slMFB during neurosurgery
Non-invasive blood pressure (mmHG)
Measured with ClearSight System, Edwards Lifesciences (allowing non-invasive and real-time continuous hemodynamic monitoring).
Measured: At test stimulation of the slMFB during neurosurgery
Cardiac stroke volume variation (%)
Measured with ClearSight System, Edwards Lifesciences (allowing non-invasive and real-time continuous hemodynamic monitoring)
Measured: At teststimulation of the slMFB during neurosurgery
Systemic vascular resistance (mmHg⋅min⋅mL-1)
Measured with ClearSight System, Edwards Lifesciences (allowing non-invasive and real-time continuous hemodynamic monitoring).
Measured: At test stimulation of the slMFB during neurosurgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2019
- Study start1 Aug 2019
- Primary completionJun 2022 (estimated)
- Study completionJun 2023 (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 Treatment Resistant DepressionStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Freiburg
- Sponsor type
- University, hospital or other
- Collaborators
- German Center for Neurodegenerative Diseases (DZNE), University Medical Center Freiburg, University Hospital, Bonn, University of Freiburg
- Responsible party
- Principal investigator, Thomas E. Schlaepfer, Prof. Dr., University Hospital Freiburg
- Investigators
- Thomas E. Schläpfer, Prof. Dr., Principal investigator, University of Freiburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04021823
- Sponsor's protocol ID
- 40418
- Status last verified
- Nov 2020
- First submitted
- 24 Jun 2019
- Last updated
- 10 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Spanier S, Kilian HM, Meyer DM, Schlaepfer TE. Treatment resistance in major depression is correlated with increased plasma levels of neurofilament light protein reflecting axonal damage. Med Hypotheses. 2019 Jun;127:159-161. doi: 10.1016/j.mehy.2019.03.022. Epub 2019 Mar 23.
PubMed 31088642
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurobiological Analyses Within the FORESEE III Study
- ClinicalTrials.gov ID
- NCT04021823
- Acronym / sponsor ID
- 40418
- Conditions
- Treatment Resistant Depression
- Keywords
- Treatment Resistant Depression, Neurobiological correlates of treatment resistant depression, Predictors of treatment response in DBS
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University Hospital FreiburgUniversity, hospital or other
- Collaborators
- German Center for Neurodegenerative Diseases (DZNE), University Medical Center Freiburg, University Hospital, Bonn, University of Freiburg
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- Jun 2022 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 16 Jul 2019 (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.
In this observational, non-invasive clinical study different neurobiological analyses will be performed in a group of patients with severe treatment resistant major depression participating in an efficacy study of deep brain stimulation of the superolateral branch of the medial forebrain bundle (slMFB) - FORESEE III.
Detailed description
This study is a sub-project of the FORESEE III study (Controlled Randomized Clinical Trial to assess Efficacy of Deep Brain Stimulation (DBS) of the slMFB in Patients with Treatment Resistant Major Depression). The FORESEE III study itself is a randomized, sham-controlled, double blind (patient and observer blinded) clinical trial to assess the antidepressant effect of DBS compared to sham.
The aim of this sub-project is to analyze the time-course of biological correlates of treatment resistant major depression as well as neurobiological markers of treatment response to treatment with DBS in a well-characterized patient population during 12 month of DBS.
Specific neurobiological analyses include testing of
- epigenetic markers (DNA methylation in candidate genes of depression and epigenome-wide association studies, EWAS)
- markers of neuroinflammation (cytokines, neuropeptides and other immune factors)
- micro RNAs and transcriptome signatures
- markers of neurodegeneration (neurofilament light protein)
- metabolomic analyses and
- endocrinological parameters including glucose tolerance.
All markers will be tested in blood samples (and urine samples for metaboloic profiling) before neurosurgery as well as at several time points during DBS and sham condition intervals.
Additionally hemodynamic parameters will be analysed at test stimulation of the slMFB during neurosurgery.
The results will be correlated with clinical and other biological response parameters of the FORESEE III study and are hypothesized to indicate treatment response as well as allowing prediction of response to DBS. All neurobiological analyses will be linked in a tightly integrated and comprehensive translational approach.
Further, a volunteer group of healthy controls will be recruited and tested for blood-markers of neurodegeneration (neurofilament light protein, 4.) as well as metabolomic analyses in blood and urine (5.).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DBS patients | – | –Patients with treatment resistant major depression participating in the FORESEE III study. |
| Healthy controls | – | –Age- and sex-matched healthy controls undergoing analyses of neurodegenerative markers (neurofilament light protein) in blood and metabolomic analyses in blood and urine. |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Eligible participants are patients who participate in the FORESEE III study (NCT03653858) and have provided written informed consent to take part in this additional observational study. All patients suffering from severe, treatment-resistant depression, i.e. patients who have not sufficiently improved under established antidepressant therapies (such as psychotherapy, antidepressant drug therapy, and electroconvulsive therapy). As well as age- and sex-matched healthy controls.
Key inclusion criteria (2 listed)
- All enrolled subjects of the Controlled Randomized Clinical Trial to assess Efficacy of Deep Brain Stimulation (DBS) of the slMFB in Patients with Treatment Resistant Major Depression (FORESEE III) may participate in this study.
- All healthy volunteers without any clinically significant psychiatric or somatic symptoms are eligible.
Key exclusion criteria (6 listed)
- Non-Caucasian (because of requirements for genetic/epigenetic analyses)
- Somatic diseases like diabetes, cancer and severe liver- and kidney-diseases
- Any clinically significant psychiatric symptoms
- Conditions like diabetes, cancer or severe liver- and kidney diseases
- Drug or alcohol abuse
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change from baseline in DNA methylation patterns in plasma at 1 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 1 month of DBS (week 5 group A, week 21 group B)
Epigenetic mechanisms such as DNA methylation crucially govern gene function and have been shown to be temporally dynamic and responsive to environmental stress. Epigenetic patterns in blood, saliva or other peripheral material have been suggested to partly reflect central epigenetic processes. DNA will by isolated and undergo bisulfite conversion. Using pyro- and direct sequencing, samples will be analyzed for DNA methylation in candidate genes of depression.
Change from baseline in DNA methylation patterns in plasma at 4 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 4 month of DBS (week 17 group A, week 33 group B)
Epigenetic mechanisms such as DNA methylation crucially govern gene function and have been shown to be temporally dynamic and responsive to environmental stress. Epigenetic patterns in blood, saliva or other peripheral material have been suggested to partly reflect central epigenetic processes. DNA will by isolated and undergo bisulfite conversion. Using pyro- and direct sequencing, samples will be analyzed for DNA methylation in candidate genes of depression.
Change from baseline in DNA methylation patterns in plasma at 12 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 12 month of DBS (end of study both groups)
Epigenetic mechanisms such as DNA methylation crucially govern gene function and have been shown to be temporally dynamic and responsive to environmental stress. Epigenetic patterns in blood, saliva or other peripheral material have been suggested to partly reflect central epigenetic processes. DNA will by isolated and undergo bisulfite conversion. Using pyro- and direct sequencing, samples will be analyzed for DNA methylation in candidate genes of depression.
Change from baseline in neuroinflammatory and neuropeptide patterns at 1 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 1 month of DBS (week 5 group A, week 21 group B)
A new method of analysis (Proseek® Multiplex Inflammation, Olink Bioscience, Uppsala, Sweden) will be used to determine any change in patterns of relevant neuropeptides and inflammatory markers. This multiplex proximity extension assay (PEA) will simultaneously analyze 92 different proteins, including cytokines, neuropeptides and other immune factors.
Change from baseline in neuroinflammatory and neuropeptide patterns at 4 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 4 month of DBS (week 17 group A, week 33 group B)
A new method of analysis (Proseek® Multiplex Inflammation, Olink Bioscience, Uppsala, Sweden) will be used to determine any change in patterns of relevant neuropeptides and inflammatory markers. This multiplex proximity extension assay (PEA) will simultaneously analyze 92 different proteins, including cytokines, neuropeptides and other immune factors.
Change from baseline in neuroinflammatory and neuropeptide patterns at 12 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 12 month of DBS (end of study both groups)
A new method of analysis (Proseek® Multiplex Inflammation, Olink Bioscience, Uppsala, Sweden) will be used to determine any change in patterns of relevant neuropeptides and inflammatory markers. This multiplex proximity extension assay (PEA) will simultaneously analyze 92 different proteins, including cytokines, neuropeptides and other immune factors.
Change from baseline in transcriptome profiles at 1 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 1 month of DBS (week 5 group A, week 21 group B)
A massive parallel next generation deep sequencing (NGS) technology will be used followed by bioinformatic network analysis to determine intraindividual changes in exosomal miR ( (miRs, 19-22 nt long non-coding RNAs) and transcriptome profiles.
Change from baseline in exosomal Micro-RNA (miR) expression levels and transcriptome profiles at 4 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 4 month of DBS (week 17 group A, week 33 group B)
A massive parallel next generation deep sequencing (NGS) technology will be used followed by bioinformatic network analysis to determine intraindividual changes in exosomal miR ( (miRs, 19-22 nt long non-coding RNAs) and transcriptome profiles.
Change from baseline in exosomal Micro-RNA (miR) expression levels and transcriptome profiles at 12 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 12 month of DBS (end of study both groups)
A massive parallel next generation deep sequencing (NGS) technology will be used followed by bioinformatic network analysis to determine intraindividual changes in exosomal miR ( (miRs, 19-22 nt long non-coding RNAs) and transcriptome profiles.
Change from baseline in plasma levels of Neurofilament light protein at 2 days before surgical device implantation
Time frame: At baseline (up to 10 to 7 weeks before surgical device implantation) and at 2 days before surgical device implantation
Neurofilament light protein is part of the neuroaxonal cytoskeleton and can be released into plasma following neuroaxonal damage. In plasma it will be measured by single-molecule array (SiMoA) assays.
Change from baseline in plasma levels of Neurofilament light protein at 1 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 1 month of DBS (week 5 group A, week 21 group B)
Neurofilament light protein is part of the neuroaxonal cytoskeleton and can be released into plasma following neuroaxonal damage. In plasma it will be measured by single-molecule array (SiMoA) assays.
Change from baseline in plasma levels of Neurofilament light protein at 4 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 4 month of DBS (week 17 group A, week 33 group B)
Neurofilament light protein is part of the neuroaxonal cytoskeleton and can be released into plasma following neuroaxonal damage. In plasma it will be measured by single-molecule array (SiMoA) assays.
Change from baseline in plasma levels of Neurofilament light protein at 12 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 12 month of DBS (end of study both groups)
Neurofilament light protein is part of the neuroaxonal cytoskeleton and can be released into plasma following neuroaxonal damage. In plasma it will be measured by single-molecule array (SiMoA) assays.
Change from baseline in metabolite profiles in plasma and urine at 1 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 1 month of DBS (week 5 group A, week 21 group B)
Metabolite profiles of plasma and urine samples will be analysed by chromatographic separation techniques, different mass spectrometric ionization modes and mass analyzers in order to assess molecular changes in the metabolome. The metabolomic methodologies may include fingerprinting, nontargeted, and targeted approaches, metabolic profiling and metabolic flux analysis.
Change from baseline in metabolite profiles in plasma and urine at 4 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 4 month of DBS (week 17 group A, week 33 group B)
Metabolite profiles of plasma and urine samples will be analysed by chromatographic separation techniques, different mass spectrometric ionization modes and mass analyzers in order to assess molecular changes in the metabolome. The metabolomic methodologies may include fingerprinting, nontargeted, and targeted approaches, metabolic profiling and metabolic flux analysis.
Change from baseline in metabolite profiles in plasma and urine at 12 month of deep brain stimulation (DBS)
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at 12 month of DBS (end of study both groups)
Metabolite profiles of plasma and urine samples will be analysed by chromatographic separation techniques, different mass spectrometric ionization modes and mass analyzers in order to assess molecular changes in the metabolome. The metabolomic methodologies may include fingerprinting, nontargeted, and targeted approaches, metabolic profiling and metabolic flux analysis.
Change from baseline in insuline resistance at week 41
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at week 41 (both groups)
An oral glucose tolerance test with blood measures of glucose, insulin and c-peptide at several time points during a period of 3 hours after oral intake of 75g glucose will be performed.
Change from baseline in systemic metabolic parameters at week 41
Time frame: At baseline (up to 10 weeks before surgical device implantation) and at week 41 (both groups)
Different systemic metabolic parameters will be measured in blood.
Cardiac stroke volume (ml)
Time frame: At test stimulation of the slMFB during neurosurgery
Measured with ClearSight System, Edwards Lifesciences (allowing non-invasive and real-time continuous hemodynamic monitoring).
Non-invasive blood pressure (mmHG)
Time frame: At test stimulation of the slMFB during neurosurgery
Measured with ClearSight System, Edwards Lifesciences (allowing non-invasive and real-time continuous hemodynamic monitoring).
Cardiac stroke volume variation (%)
Time frame: At teststimulation of the slMFB during neurosurgery
Measured with ClearSight System, Edwards Lifesciences (allowing non-invasive and real-time continuous hemodynamic monitoring)
Systemic vascular resistance (mmHg⋅min⋅mL-1)
Time frame: At test stimulation of the slMFB during neurosurgery
Measured with ClearSight System, Edwards Lifesciences (allowing non-invasive and real-time continuous hemodynamic monitoring).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2020.
- Background: PubMed 31088642Spanier S, Kilian HM, Meyer DM, Schlaepfer TE. Treatment resistance in major depression is correlated with increased plasma levels of neurofilament light protein reflecting axonal damage. Med Hypotheses. 2019 Jun;127:159-161. doi: 10.1016/j.mehy.2019.03.022. Epub 2019 Mar 23.
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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.
Thomas E. Schläpfer, Prof. Dr. principal investigator
University of Freiburg
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 Treatment Resistant Depression, run by University Hospital Freiburg at 1 site in Germany.
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 2 inclusion and 6 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 10 Nov 2020. 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 Germany. 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 Susanne Spanier (+49 761 270 69800, susanne.spanier@uniklinik-freiburg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in DNA methylation patterns in plasma at 1 month of deep brain stimulation (DBS) (time frame: At baseline (up to 10 weeks before surgical device implantation) and at 1 month of DBS (week 5 group A, week 21 group B)). The study lists 22 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 NCT04021823, 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 10 Nov 2020.