Major Depressive DisorderMRSDC1NCT02715128
Disorder-tailored Transcranial Direct Current Stimulation (tDCS) of the Prefrontal Cortex
A study testing Transcranial direct current stimulation (tDCS) in people with Major Depressive Disorder and Schizophrenia, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.
Trial summary
Major depressive disorder (MDD) is a common, recurrent, and frequent chronic disorder. Among others, deficient cognitive control over emotional distraction is a central characteristic of MDD (Ochsner \& Gross 2005; Disner et al. 2011; Beck 2008). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder, Schizophrenia
- What is being tested?
- Transcranial direct current stimulation (tDCS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteGermany
- Study dates
- Mar 2016to Jan 2022
- Phase
- Interventional
- 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
Who may be able to join
- Men and women 18-60 years of age.
- Capable and willing to provide informed consent.
- MDD: Primary ICD-10 diagnosis of Major Depression and a total HDRS-21 ≥15 and/or BDI ≥15 at the screening visit; no antidepressant medication and stable medication ≥4 days before study onset and during study period.
- SCZ: Primary ICD10 diagnosis of Schizophrenia and a stable antipsychotic medication ≥1 weeks before study onset and during study period.
Who cannot join
- Contraindications for brain stimulation, such as history of brain surgery or severe brain injury, as well as contraindications for MRI, such as metallic implants, any other non-MR safe implants, or claustrophobia.
- Investigators, site personnel directly affiliated with this study, and their immediate families (immediate family is defined as a spouse, parent, child or sibling, whether by birth or legal adoption).
- Acute risk for suicide (MADRS, item 10 score of >4 or as assessed by the C-SSRS, agree to item 4 and/or agree to item 5).
- Treatment with electroconvulsive therapy in the present episode.
- Treatment with deep brain stimulation or vagus nerve stimulation and/or any other intracranial implants (clips, cochlear implants).
- Any other relevant psychiatric axis-I- and/or axis-II-disorder.
- Any relevant instable medical condition.
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University Munich
Munich, 80336
Daniel Keeser, Dr., +40 (0)89 44005755, daniel.keeser@med.uni-muenchen.de
Lucia Bulubas, Dr. med., +40 (0)89 440055821, lucia.bulubas@med.uni-muenchen.de
About this study
Official title: Disorder-tailored Transcranial Direct Current Stimulation (tDCS) of the Prefrontal Cortex: fMRI Study in Major Depression and Schizophrenia
Major depressive disorder (MDD) is a common, recurrent, and frequent chronic disorder. Among others, deficient cognitive control over emotional distraction is a central characteristic of MDD (Ochsner \& Gross 2005; Disner et al. 2011; Beck 2008). Hypoactivation of the dorsolateral prefrontal cortex (DLPFC) has been linked with this deficit (Dolcos \& McCarthy 2006). Moreover, aberrant functional connectivity patterns have been found in MDD patients (Kaiser et al. 2015). Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method that has been largely investigated in experimental neurosciences and tDCS of the prefrontal cortex (PFC) has been proposed as novel treatment in MDD. In addition, it is increasingly investigated as treatment for negative symptoms in schizophrenia (SCZ) (Brunelin et al. 2012). So far, prefrontal tDCS has been shown to enhance cognitive control over emotional distraction in MDD patients (Wokenstein \& Plewnia 2013). Also, tDCS-induced connectivity changes found in fMRI studies comparing resting-state networks configurations before and after prefrontal tDCS may reflect a state of enhanced alertness (Keeser, Meindl, et al., 2011; Park et al., 2013).
The aim of this study is to investigate the neurophysiological correlates of tDCS effects in patients with different psychiatric disorders for which tDCS is a possible intervention, in particular MDD and SCZ, as compared to healthy individuals. For this purpose, we determine the most promising protocol in from investigations in healthy volunteers and apply this protocol in the patient sample including age- and gender-matched controls. First, functional magnetic resonance imaging (fMRI) data is collected during the execution of a cognitive control task as well as during a resting-state condition together with application of real or sham tDCS inside the scanner. It is hypothesized that prefrontal tDCS as compared to sham a) reduces distractibility by compensating for deficient DLPFC activity and b) enhances functional connectivity in networks associated with externally directed attention or cognitive engagement. Second, magnetic resonance spectroscopy (MRS) is performed to measure concentrations of GABA and glutamate in target regions of tDCS. It is hypothesized that tDCS effects are mediated via modulation of the inhibitory/excitatory systems and GABA and glutamate are used as markers of these systems.
In this placebo-controlled study healthy volunteers and patients with a diagnosis of MDD or SCZ receive a single treatment with prefrontal tDCS (anode over electrode position F3, cathode over F4, 20 min, 2mA intensity) or sham tDCS (frequency and duration correspondent active tDCS, ramp in and ramp out periods only without intermittent stimulation). We conduct resting-state and MRS measurements combined with application of tDCS in the fMRI scanner. Subsequently, participants perform the cognitive control task (in dependence of Plewnia, C., Schroeder, P. A., \& Wolkenstein, L. (2015)) in the scanner. The participants are assigned to either the real or sham tDCS condition according to a randomised, double-blind parallel design.
- Conditions
- Major Depressive Disorder, Schizophrenia
- Being tested
- Transcranial direct current stimulation (tDCS)
- Medical subject headings
- Depressive Disorder, Major, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial direct current stimulation (tDCS)Device
non-invasive electric brain stimulation method
| Study group | Role | What they receive |
|---|---|---|
| real tDCS | Active comparator | anode over electrode position F3, cathode over F4, 20 min, 2mA intensity Receives: Device: Transcranial direct current stimulation (tDCS) |
| sham tDCS | Sham comparator | frequency and duration correspondent active tDCS, ramp in and ramp out periods only without intermittent stimulation Receives: Device: Transcranial direct current stimulation (tDCS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
FMRI modulations
differences in the cognitive control task (performance and activations) between the sham and real group as well as changes in resting-state connectivity between and within (following stimulation compared to baseline) groups
Measured: 2 hours
GABA and Glutamate modulations
differences in excitatory and inhibitory system modulation visualised via GABA and Glutamate concentrations determined by H1-MRS measurements
Measured: 2 hours
Secondary outcomes (1)
Clinical trajectories
Influence of observed online modulatory effects on clinical trajectories in patients
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2016 (estimated)
- Study startMar 2016
- Primary completionJan 2021 (estimated)
- Study completionJan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ludwig-Maximilians - University of Munich
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Keeser, Ludwig-Maximilians - University of Munich
- Investigators
- Frank Padberg, Prof. Dr., Principal investigator, Ludwig-Maximilians-Universität München
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02715128
- Sponsor's protocol ID
- 493-14
- Acronym
- MRSDC1
- Status last verified
- May 2020
- First submitted
- 16 Mar 2016
- Last updated
- 2 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Keeser D, Meindl T, Bor J, Palm U, Pogarell O, Mulert C, Brunelin J, Moller HJ, Reiser M, Padberg F. Prefrontal transcranial direct current stimulation changes connectivity of resting-state networks during fMRI. J Neurosci. 2011 Oct 26;31(43):15284-93. doi: 10.1523/JNEUROSCI.0542-11.2011.
PubMed 22031874Park CH, Chang WH, Park JY, Shin YI, Kim ST, Kim YH. Transcranial direct current stimulation increases resting state interhemispheric connectivity. Neurosci Lett. 2013 Feb 28;539:7-10. doi: 10.1016/j.neulet.2013.01.047. Epub 2013 Feb 13.
PubMed 23416318Kaiser RH, Andrews-Hanna JR, Wager TD, Pizzagalli DA. Large-Scale Network Dysfunction in Major Depressive Disorder: A Meta-analysis of Resting-State Functional Connectivity. JAMA Psychiatry. 2015 Jun;72(6):603-11. doi: 10.1001/jamapsychiatry.2015.0071.
PubMed 25785575Ochsner KN, Gross JJ. The cognitive control of emotion. Trends Cogn Sci. 2005 May;9(5):242-9. doi: 10.1016/j.tics.2005.03.010.
PubMed 15866151Disner SG, Beevers CG, Haigh EA, Beck AT. Neural mechanisms of the cognitive model of depression. Nat Rev Neurosci. 2011 Jul 6;12(8):467-77. doi: 10.1038/nrn3027.
PubMed 21731066Beck AT. The evolution of the cognitive model of depression and its neurobiological correlates. Am J Psychiatry. 2008 Aug;165(8):969-77. doi: 10.1176/appi.ajp.2008.08050721. Epub 2008 Jul 15.
PubMed 18628348Dolcos F, McCarthy G. Brain systems mediating cognitive interference by emotional distraction. J Neurosci. 2006 Feb 15;26(7):2072-9. doi: 10.1523/JNEUROSCI.5042-05.2006.
PubMed 16481440Wolkenstein L, Plewnia C. Amelioration of cognitive control in depression by transcranial direct current stimulation. Biol Psychiatry. 2013 Apr 1;73(7):646-51. doi: 10.1016/j.biopsych.2012.10.010. Epub 2012 Dec 6.
PubMed 23219367Plewnia C, Schroeder PA, Wolkenstein L. Targeting the biased brain: non-invasive brain stimulation to ameliorate cognitive control. Lancet Psychiatry. 2015 Apr;2(4):351-6. doi: 10.1016/S2215-0366(15)00056-5. Epub 2015 Mar 31.
PubMed 26360088Brunelin J, Mondino M, Gassab L, Haesebaert F, Gaha L, Suaud-Chagny MF, Saoud M, Mechri A, Poulet E. Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Am J Psychiatry. 2012 Jul;169(7):719-24. doi: 10.1176/appi.ajp.2012.11071091.
PubMed 22581236
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Disorder-tailored Transcranial Direct Current Stimulation (tDCS) of the Prefrontal Cortex: fMRI Study in Major Depression and Schizophrenia
- ClinicalTrials.gov ID
- NCT02715128
- Acronym / sponsor ID
- MRSDC1 / 493-14
- Conditions
- Major Depressive Disorder, Schizophrenia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Ludwig-Maximilians - University of MunichUniversity, hospital or other
- Study start
- Mar 2016 (actual)
- Primary completion
- Jan 2021 (estimated)
- Study completion
- Jan 2022 (estimated)
- First posted
- 22 Mar 2016 (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.
Major depressive disorder (MDD) is a common, recurrent, and frequent chronic disorder. Among others, deficient cognitive control over emotional distraction is a central characteristic of MDD (Ochsner \& Gross 2005; Disner et al. 2011; Beck 2008). Hypoactivation of the dorsolateral prefrontal cortex (DLPFC) has been linked with this deficit (Dolcos \& McCarthy 2006). Moreover, aberrant functional connectivity patterns have been found in MDD patients (Kaiser et al. 2015). Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method that has been largely investigated in experimental neurosciences and tDCS of the prefrontal cortex (PFC) has been proposed as novel treatment in MDD. In addition, it is increasingly investigated as treatment for negative symptoms in schizophrenia (SCZ) (Brunelin et al. 2012). So far, prefrontal tDCS has been shown to enhance cognitive control over emotional distraction in MDD patients (Wokenstein \& Plewnia 2013). Also, tDCS-induced connectivity changes found in fMRI studies comparing resting-state networks configurations before and after prefrontal tDCS may reflect a state of enhanced alertness (Keeser, Meindl, et al., 2011; Park et al., 2013).
The aim of this study is to investigate the neurophysiological correlates of tDCS effects in patients with different psychiatric disorders for which tDCS is a possible intervention, in particular MDD and SCZ, as compared to healthy individuals. For this purpose, we determine the most promising protocol in from investigations in healthy volunteers and apply this protocol in the patient sample including age- and gender-matched controls. First, functional magnetic resonance imaging (fMRI) data is collected during the execution of a cognitive control task as well as during a resting-state condition together with application of real or sham tDCS inside the scanner. It is hypothesized that prefrontal tDCS as compared to sham a) reduces distractibility by compensating for deficient DLPFC activity and b) enhances functional connectivity in networks associated with externally directed attention or cognitive engagement. Second, magnetic resonance spectroscopy (MRS) is performed to measure concentrations of GABA and glutamate in target regions of tDCS. It is hypothesized that tDCS effects are mediated via modulation of the inhibitory/excitatory systems and GABA and glutamate are used as markers of these systems.
In this placebo-controlled study healthy volunteers and patients with a diagnosis of MDD or SCZ receive a single treatment with prefrontal tDCS (anode over electrode position F3, cathode over F4, 20 min, 2mA intensity) or sham tDCS (frequency and duration correspondent active tDCS, ramp in and ramp out periods only without intermittent stimulation). We conduct resting-state and MRS measurements combined with application of tDCS in the fMRI scanner. Subsequently, participants perform the cognitive control task (in dependence of Plewnia, C., Schroeder, P. A., \& Wolkenstein, L. (2015)) in the scanner. The participants are assigned to either the real or sham tDCS condition according to a randomised, double-blind parallel design.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| real tDCS | Active comparator | Device: Transcranial direct current stimulation (tDCS)anode over electrode position F3, cathode over F4, 20 min, 2mA intensity |
| sham tDCS | Sham comparator | Device: Transcranial direct current stimulation (tDCS)frequency and duration correspondent active tDCS, ramp in and ramp out periods only without intermittent stimulation |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men and women 18-60 years of age.
- Capable and willing to provide informed consent.
- MDD: Primary ICD-10 diagnosis of Major Depression and a total HDRS-21 ≥15 and/or BDI ≥15 at the screening visit; no antidepressant medication and stable medication ≥4 days before study onset and during study period.
- SCZ: Primary ICD10 diagnosis of Schizophrenia and a stable antipsychotic medication ≥1 weeks before study onset and during study period.
Key exclusion criteria (8 listed)
- Contraindications for brain stimulation, such as history of brain surgery or severe brain injury, as well as contraindications for MRI, such as metallic implants, any other non-MR safe implants, or claustrophobia.
- Investigators, site personnel directly affiliated with this study, and their immediate families (immediate family is defined as a spouse, parent, child or sibling, whether by birth or legal adoption).
- Acute risk for suicide (MADRS, item 10 score of >4 or as assessed by the C-SSRS, agree to item 4 and/or agree to item 5).
- Treatment with electroconvulsive therapy in the present episode.
- Treatment with deep brain stimulation or vagus nerve stimulation and/or any other intracranial implants (clips, cochlear implants).
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 |
|---|---|---|
| Transcranial direct current stimulation (tDCS)non-invasive electric brain stimulation method | Device | real tDCS, sham tDCS |
Primary outcome
FMRI modulations
Time frame: 2 hours
differences in the cognitive control task (performance and activations) between the sham and real group as well as changes in resting-state connectivity between and within (following stimulation compared to baseline) groups
GABA and Glutamate modulations
Time frame: 2 hours
differences in excitatory and inhibitory system modulation visualised via GABA and Glutamate concentrations determined by H1-MRS measurements
1 secondary outcome
Clinical trajectories
Time frame: 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2020.
- Background: PubMed 22031874Keeser D, Meindl T, Bor J, Palm U, Pogarell O, Mulert C, Brunelin J, Moller HJ, Reiser M, Padberg F. Prefrontal transcranial direct current stimulation changes connectivity of resting-state networks during fMRI. J Neurosci. 2011 Oct 26;31(43):15284-93. doi: 10.1523/JNEUROSCI.0542-11.2011.
- Background: PubMed 23416318Park CH, Chang WH, Park JY, Shin YI, Kim ST, Kim YH. Transcranial direct current stimulation increases resting state interhemispheric connectivity. Neurosci Lett. 2013 Feb 28;539:7-10. doi: 10.1016/j.neulet.2013.01.047. Epub 2013 Feb 13.
- Background: PubMed 25785575Kaiser RH, Andrews-Hanna JR, Wager TD, Pizzagalli DA. Large-Scale Network Dysfunction in Major Depressive Disorder: A Meta-analysis of Resting-State Functional Connectivity. JAMA Psychiatry. 2015 Jun;72(6):603-11. doi: 10.1001/jamapsychiatry.2015.0071.
- Background: PubMed 15866151Ochsner KN, Gross JJ. The cognitive control of emotion. Trends Cogn Sci. 2005 May;9(5):242-9. doi: 10.1016/j.tics.2005.03.010.
- Background: PubMed 21731066Disner SG, Beevers CG, Haigh EA, Beck AT. Neural mechanisms of the cognitive model of depression. Nat Rev Neurosci. 2011 Jul 6;12(8):467-77. doi: 10.1038/nrn3027.
- Background: PubMed 18628348Beck AT. The evolution of the cognitive model of depression and its neurobiological correlates. Am J Psychiatry. 2008 Aug;165(8):969-77. doi: 10.1176/appi.ajp.2008.08050721. Epub 2008 Jul 15.
- Background: PubMed 16481440Dolcos F, McCarthy G. Brain systems mediating cognitive interference by emotional distraction. J Neurosci. 2006 Feb 15;26(7):2072-9. doi: 10.1523/JNEUROSCI.5042-05.2006.
- Background: PubMed 23219367Wolkenstein L, Plewnia C. Amelioration of cognitive control in depression by transcranial direct current stimulation. Biol Psychiatry. 2013 Apr 1;73(7):646-51. doi: 10.1016/j.biopsych.2012.10.010. Epub 2012 Dec 6.
- Background: PubMed 26360088Plewnia C, Schroeder PA, Wolkenstein L. Targeting the biased brain: non-invasive brain stimulation to ameliorate cognitive control. Lancet Psychiatry. 2015 Apr;2(4):351-6. doi: 10.1016/S2215-0366(15)00056-5. Epub 2015 Mar 31.
- Background: PubMed 22581236Brunelin J, Mondino M, Gassab L, Haesebaert F, Gaha L, Suaud-Chagny MF, Saoud M, Mechri A, Poulet E. Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Am J Psychiatry. 2012 Jul;169(7):719-24. doi: 10.1176/appi.ajp.2012.11071091.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Frank Padberg, Prof. Dr. principal investigator
Ludwig-Maximilians-Universität München
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial direct current stimulation (tDCS) in people with Major Depressive Disorder and Schizophrenia, run by Ludwig-Maximilians - University of Munich 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 4 inclusion and 8 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 2 Jun 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. Some participants in this study may receive a placebo. 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 Frank Padberg, Prof. Dr. (+40 (0)89 440053358, frank.padberg@med.uni-muenchen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FMRI modulations (time frame: 2 hours). 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 NCT02715128, which also lists 10 linked publications.
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 Jun 2020.