Major DepressionNCT02379767
Effects of ECT on Monoamine Oxidase A in Depression Investigated With PET
An observational study of Major Depression, run by Medical University of Vienna at 1 site in Austria.
Trial summary
This study aims at evaluating the effect of electroconvulsive therapy in treatment-resistant depressed patients on the major serotonin degrading enzyme in the human brain using neuroimaging methods, the monoamine oxidase A. Electroconvulsive therapy is an effective treatment option in severe cases of depression. Read more about this study
- Who is it for?
- Ages 16 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depression
- What is being tested?
- Electroconvulsive therapy, Positron emission tomography of the brain using [11C]harmine and Structural magnetic resonance imaging
- Type of treatment
- Medical device
- How many people
- 27 participants
- Where
- 1 siteAustria
- Study dates
- Mar 2015to 25 May 2018
- 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 16 to 60 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: 18 patients with severe unipolar depression determined by a structured clinical interview for DSM-IV (SCID) and the 17-item Hamilton Rating Scale for Depression (HAM-D score ≥ 23) who did not respond to conventional pharmacological antidepressant treatment (at least two adequate trials with antidepressants of different pharmacological classes over a minimum period of one month, equivalent to 150mg of tricyclic antidepressants) will be recruited at the Department of Psychiatry and Psychotherapy at the General Hospital of Vienna. Additionally, 18 healthy age- and sex-matched controls will participate in this longitudinal study.
Who may be able to join
- Male or female
- Age 18 - 60 years
- ICD-10 diagnosis of severe unipolar depression (ICD-10: F32.2, F32.3; F33.2, F33.3)
- A score of 23 or greater on the 17-item HAM-D
- Signed informed consent form
- Negative urine pregnancy test in women at the screening visit and at PET/MRI days
Show all 15Show fewer
- Antidepressant and antipsychotic medication in a steady state for at least 10 days prior to inclusion
- Anesthesiological approval for ECT
- Relatively stable mental state which allows for a potential latency period of 10 days until inclusion as concomitant medication must be in steady-state for a minimum of 10 days prior ECT.
- Male or female
- Age 18 - 60 years
- Somatic health based on history, physical examination, ECG, and laboratory screening
- A maximum of 7 points on the 17-item HAM-D
- Signed informed consent form
- Negative urine pregnancy test in women at the screening visit and at PET/MRI days
Who cannot join
- Concomitant major internistic or neurological illness
- Clinically relevant abnormalities on a general physical examination and routine laboratory screening
- Current substance abuse, including nicotine
- Current or past history of schizophrenia or schizoaffective disorder
- For participants who participated in an earlier neuroimaging study using ionizing radiation, the total radiation exposure dose of 20 mSv over the last 10 years must not be exceeded, as specified in the legislation on radiation protection (Allg. Strahlenschutzverordnung 2010; www.ris.bka.gv.at).
- Presence of any metallic implant contraindicated for MRI
Show all 9Show fewer
- Previous treatments with electroconvulsive therapy
- Treatment (< 1 months before screening) with bright light therapy
- Treatment (< 1 months before screening) with drugs directly affecting the density and/or activity of monoamine oxidase A, e.g. moclobemid.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Electroconvulsive Therapy on Monoamine Oxidase A Distribution Volume in Treatment-Resistant Depression Investigated With PET
This study aims at evaluating the effect of electroconvulsive therapy in treatment-resistant depressed patients on the major serotonin degrading enzyme in the human brain using neuroimaging methods, the monoamine oxidase A. Electroconvulsive therapy is an effective treatment option in severe cases of depression. However, the mechanisms underlying its effect remain uncertain, though variations within the serotonergic neurotransmitter system seem to be crucially involved.
Read the detailed description
In treatment-resistant depression, electroconvulsive therapy (ECT) has been shown to effectively reduce depressive symptoms; however, the underlying neurobiological mechanisms remain to be fully understood. Recent neuroimaging findings underline the involvement of the serotonergic system in the mechanism of action of ECT, but studies in this context mainly focused on serotonin receptor and the serotonin transporter. Here, the aim of the study is to assess the effects ECT on monoamine oxidase A (MAO-A), the main serotonin degrading enzyme which is known to be involved in antidepressant action, in humans using positron emission tomography (PET) and the radiotracer [11C]harmine. Moreover, as the antidepressant effects of electroconvulsive stimulations were shown to be partly mediated via changes in neuroplasticity, a secondary aim of the present study is to assess structural alterations caused by ECT using magnetic resonance imaging (sMRI).
Based on the literature, the investigators expect higher baseline MAO-A distribution volumes (DVs) in depressed patients than compared to healthy subjects.Moreover, the investigators expect overall MAO-A distribution volume (DVs) changes in the brain of depressed patients following ECT according to the individual treatment-response. Similarly, the investigators assume that depressed patients will exhibit structural changes of grey matter volume following ECT.
The investigation is designed as a longitudinal mono-centre study over a duration of 36 months. 18 subjects with therapy-resistant, severe unipolar depression, aged between 18-60 years and 18 age- and sex-matched healthy subjects will be included in the study. Patients will be recruited at the Department of Psychiatry and Psychotherapy, Medical University of Vienna, and will be offered inpatient care. Psychotropic medication (except for drugs directly binding MAO-A, e.g. moclobemid) of the patients is allowed if steady state has been reached > 10 days prior to inclusion. Healthy subject will be recruited using announcements of poster boards at the General Hospital of Vienna. Each patient will be measured three times using a GE Advance PET scanner and the radioligand [11C]harmine. The first and second measurements determine baseline changes in the MAO-A DVs while the third scan is used to quantify changes induced by ECT. Healthy subjects will be measured with PET only once. Similarly, patients will undergo three structural (T1-weighted) MRI sessions temporally coordinated to the PET scans. Healthy subjects will be measured with MRI only once.
Each patient will be treated in 6 to 14 ECT sessions within a time interval of 2 to 5 weeks. A brief pulse ECT machine (Thymatron System IVTM) will be used three times per week to administer treatments either unilaterally over the right hemisphere or, if required, bilaterally.
The MAO-A DVs will be determined using a region of interest and a whole brain voxel-wise approach. A repeated-measures analysis of variance (ANOVA) will compare the change in the MAO-A DVs before and after ECT (PET2-PET3) with the change between the baseline PET scans (PET1-PET2). Secondly, MAO-A DVs from PET1 will be compared to the scans of healthy subjects (cross-sectional part). Additionally, the correlation between treatment effects reflected in HAM-D score and changes in MAO-A DVs will be computed. Similar statistical analyses will be done with sMRI data.
This study would be the first to demonstrate an effect of ECT on MAO-A DVs in humans in vivo. Given the involvement of the MAO-A in the pathophysiology of mood disorders, the present study would be an important step towards a better understanding of antidepressant treatment and treatment response. By comparing treatment effects and the underlying biological mechanism, the study might help to identify biomarkers that distinguish patients who are likely to benefit from ECT from patients who will rather be non-responders. Finally, by investigating the role of the MAO-A DVs in ECT, its highly discussed relevance for antidepressant action will be further elucidated and might prepare the ground for new therapeutic strategies. Additionally, this study might contribute in substantiating potential effects of ECT on brain structure.
- Conditions
- Major Depression
- Being tested
- Electroconvulsive therapy, Positron emission tomography of the brain using [11C]harmine, Structural magnetic resonance imaging
- 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.
Electroconvulsive therapyDevice
Positron emission tomography of the brain using [11C]harmineOther
Structural magnetic resonance imagingOther
| Study group | Role | What they receive |
|---|---|---|
| Patients | Subjects aged between 18 and 60 years suffering from unipolar severe depression, who did not respond to conventional pharmacological antidepressant treatment (at least two adequate trials with antidepressants of different pharmacological classes over a minimum period of one month, equivalent to 150mg of tricyclic antidepressants). Concomitant psychotropic medication will be accepted during study participation, however, medication should remain stable throughout the study. Patients will undergo 6 to 14 ECT sessions in accordance with recent consensus statements and based on standard operation procedures (SOPs) of the Department of Psychiatry and Psychotherapy. Receives: Device: Electroconvulsive therapy; Other: Positron emission tomography of the brain using [11C]harmine; Other: Structural magnetic resonance imaging | |
| Healthy subjects | Subjects will be age- and sex-matched to the patients and should present no psychiatric, or major neurological or internistic illness. Receives: Other: Positron emission tomography of the brain using [11C]harmine; Other: Structural magnetic resonance imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Monoamine oxidase A distribution volume in the brain
MAOA DVs will be assessed using positron emission tomography
Measured: 5 weeks
Secondary outcomes (1)
Grey matter volume
Grey matter volume will be assessed using structural magnetic resonance imaging
Measured: 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2015 (estimated)
- Study startMar 2015
- Primary completion25 May 2018
- Study completion25 May 2018
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 DepressionStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- 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
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rupert Lanzenberger, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02379767
- Sponsor's protocol ID
- v1.2_201502
- Status last verified
- Aug 2019
- First submitted
- 1 Mar 2015
- Last updated
- 28 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gryglewski G, Baldinger-Melich P, Seiger R, Godbersen GM, Michenthaler P, Klobl M, Spurny B, Kautzky A, Vanicek T, Kasper S, Frey R, Lanzenberger R. Structural changes in amygdala nuclei, hippocampal subfields and cortical thickness following electroconvulsive therapy in treatment-resistant depression: longitudinal analysis. Br J Psychiatry. 2019 Mar;214(3):159-167. doi: 10.1192/bjp.2018.224. Epub 2018 Nov 16.
PubMed 30442205
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Electroconvulsive Therapy on Monoamine Oxidase A Distribution Volume in Treatment-Resistant Depression Investigated With PET
- ClinicalTrials.gov ID
- NCT02379767
- Acronym / sponsor ID
- v1.2_201502
- Conditions
- Major Depression
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- 25 May 2018 (actual)
- Study completion
- 25 May 2018 (actual)
- First posted
- 5 Mar 2015 (estimated)
- 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.
This study aims at evaluating the effect of electroconvulsive therapy in treatment-resistant depressed patients on the major serotonin degrading enzyme in the human brain using neuroimaging methods, the monoamine oxidase A. Electroconvulsive therapy is an effective treatment option in severe cases of depression. However, the mechanisms underlying its effect remain uncertain, though variations within the serotonergic neurotransmitter system seem to be crucially involved.
Detailed description
In treatment-resistant depression, electroconvulsive therapy (ECT) has been shown to effectively reduce depressive symptoms; however, the underlying neurobiological mechanisms remain to be fully understood. Recent neuroimaging findings underline the involvement of the serotonergic system in the mechanism of action of ECT, but studies in this context mainly focused on serotonin receptor and the serotonin transporter. Here, the aim of the study is to assess the effects ECT on monoamine oxidase A (MAO-A), the main serotonin degrading enzyme which is known to be involved in antidepressant action, in humans using positron emission tomography (PET) and the radiotracer [11C]harmine. Moreover, as the antidepressant effects of electroconvulsive stimulations were shown to be partly mediated via changes in neuroplasticity, a secondary aim of the present study is to assess structural alterations caused by ECT using magnetic resonance imaging (sMRI).
Based on the literature, the investigators expect higher baseline MAO-A distribution volumes (DVs) in depressed patients than compared to healthy subjects.Moreover, the investigators expect overall MAO-A distribution volume (DVs) changes in the brain of depressed patients following ECT according to the individual treatment-response. Similarly, the investigators assume that depressed patients will exhibit structural changes of grey matter volume following ECT.
The investigation is designed as a longitudinal mono-centre study over a duration of 36 months. 18 subjects with therapy-resistant, severe unipolar depression, aged between 18-60 years and 18 age- and sex-matched healthy subjects will be included in the study. Patients will be recruited at the Department of Psychiatry and Psychotherapy, Medical University of Vienna, and will be offered inpatient care. Psychotropic medication (except for drugs directly binding MAO-A, e.g. moclobemid) of the patients is allowed if steady state has been reached > 10 days prior to inclusion. Healthy subject will be recruited using announcements of poster boards at the General Hospital of Vienna. Each patient will be measured three times using a GE Advance PET scanner and the radioligand [11C]harmine. The first and second measurements determine baseline changes in the MAO-A DVs while the third scan is used to quantify changes induced by ECT. Healthy subjects will be measured with PET only once. Similarly, patients will undergo three structural (T1-weighted) MRI sessions temporally coordinated to the PET scans. Healthy subjects will be measured with MRI only once.
Each patient will be treated in 6 to 14 ECT sessions within a time interval of 2 to 5 weeks. A brief pulse ECT machine (Thymatron System IVTM) will be used three times per week to administer treatments either unilaterally over the right hemisphere or, if required, bilaterally.
The MAO-A DVs will be determined using a region of interest and a whole brain voxel-wise approach. A repeated-measures analysis of variance (ANOVA) will compare the change in the MAO-A DVs before and after ECT (PET2-PET3) with the change between the baseline PET scans (PET1-PET2). Secondly, MAO-A DVs from PET1 will be compared to the scans of healthy subjects (cross-sectional part). Additionally, the correlation between treatment effects reflected in HAM-D score and changes in MAO-A DVs will be computed. Similar statistical analyses will be done with sMRI data.
This study would be the first to demonstrate an effect of ECT on MAO-A DVs in humans in vivo. Given the involvement of the MAO-A in the pathophysiology of mood disorders, the present study would be an important step towards a better understanding of antidepressant treatment and treatment response. By comparing treatment effects and the underlying biological mechanism, the study might help to identify biomarkers that distinguish patients who are likely to benefit from ECT from patients who will rather be non-responders. Finally, by investigating the role of the MAO-A DVs in ECT, its highly discussed relevance for antidepressant action will be further elucidated and might prepare the ground for new therapeutic strategies. Additionally, this study might contribute in substantiating potential effects of ECT on brain structure.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | – | Device: Electroconvulsive therapy, Other: Positron emission tomography of the brain using [11C]harmine, Other: Structural magnetic resonance imagingSubjects aged between 18 and 60 years suffering from unipolar severe depression, who did not respond to conventional pharmacological antidepressant treatment (at least two adequate trials with antidepressants of different pharmacological classes over a minimum period of one month, equivalent to 150mg of tricyclic antidepressants). Concomitant psychotropic medication will be accepted during study participation, however, medication should remain stable throughout the study. Patients will undergo 6 to 14 ECT sessions in accordance with recent consensus statements and based on standard operation procedures (SOPs) of the Department of Psychiatry and Psychotherapy. |
| Healthy subjects | – | Other: Positron emission tomography of the brain using [11C]harmine, Other: Structural magnetic resonance imagingSubjects will be age- and sex-matched to the patients and should present no psychiatric, or major neurological or internistic illness. |
Who may qualify
- Ages
- 16 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- 18 patients with severe unipolar depression determined by a structured clinical interview for DSM-IV (SCID) and the 17-item Hamilton Rating Scale for Depression (HAM-D score ≥ 23) who did not respond to conventional pharmacological antidepressant treatment (at least two adequate trials with antidepressants of different pharmacological classes over a minimum period of one month, equivalent to 150mg of tricyclic antidepressants) will be recruited at the Department of Psychiatry and Psychotherapy at the General Hospital of Vienna. Additionally, 18 healthy age- and sex-matched controls will participate in this longitudinal study.
Key inclusion criteria (15 listed)
- Male or female
- Age 18 - 60 years
- ICD-10 diagnosis of severe unipolar depression (ICD-10: F32.2, F32.3; F33.2, F33.3)
- A score of 23 or greater on the 17-item HAM-D
- Signed informed consent form
Key exclusion criteria (9 listed)
- Concomitant major internistic or neurological illness
- Clinically relevant abnormalities on a general physical examination and routine laboratory screening
- Current substance abuse, including nicotine
- Current or past history of schizophrenia or schizoaffective disorder
- For participants who participated in an earlier neuroimaging study using ionizing radiation, the total radiation exposure dose of 20 mSv over the last 10 years must not be exceeded, as specified in the legislation on radiation protection (Allg. Strahlenschutzverordnung 2010; www.ris.bka.gv.at).
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 |
|---|---|---|
| Electroconvulsive therapy | Device | Patients |
| Positron emission tomography of the brain using [11C]harmine | Other | Healthy subjects, Patients |
| Structural magnetic resonance imaging | Other | Healthy subjects, Patients |
Primary outcome
Monoamine oxidase A distribution volume in the brain
Time frame: 5 weeks
MAOA DVs will be assessed using positron emission tomography
1 secondary outcome
Grey matter volume
Time frame: 5 weeks
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 28 Aug 2019.
- Derived from this study: PubMed 30442205Gryglewski G, Baldinger-Melich P, Seiger R, Godbersen GM, Michenthaler P, Klobl M, Spurny B, Kautzky A, Vanicek T, Kasper S, Frey R, Lanzenberger R. Structural changes in amygdala nuclei, hippocampal subfields and cortical thickness following electroconvulsive therapy in treatment-resistant depression: longitudinal analysis. Br J Psychiatry. 2019 Mar;214(3):159-167. doi: 10.1192/bjp.2018.224. Epub 2018 Nov 16.
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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 Major Depression, run by Medical University of Vienna at 1 site in Austria.
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 15 inclusion and 9 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 28 Aug 2019. 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 Austria. 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?
Monoamine oxidase A distribution volume in the brain (time frame: 5 weeks). 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 NCT02379767, 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 28 Aug 2019.