Disorder-tailored Transcranial Direct Current Stimulation (tDCS) of the Prefrontal Cortex

NCT02715128 | Unknown

• 1 other identifier: 493-14
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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). 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

Outcome Measures

Primary Outcomes (2)

• 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

  2 hours

• GABA and Glutamate modulations

  differences in excitatory and inhibitory system modulation visualised via GABA and Glutamate concentrations determined by H1-MRS measurements

  2 hours

Secondary Outcomes (1)

• Clinical trajectories

  8 weeks

Study Arms (2)

real tDCS

ACTIVE COMPARATOR

anode over electrode position F3, cathode over F4, 20 min, 2mA intensity

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

Device: Transcranial direct current stimulation (tDCS)

Interventions

Transcranial direct current stimulation (tDCS) DEVICE

non-invasive electric brain stimulation method

real tDCS; sham tDCS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead

Study Sites (1)

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University Munich

Munich, 80336, Germany

RECRUITING

Related Publications (10)

• 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.

  PMID: 22031874 BACKGROUND

• Park 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.

  PMID: 23416318 BACKGROUND

• Kaiser 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.

  PMID: 25785575 BACKGROUND

• Ochsner 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.

  PMID: 15866151 BACKGROUND

• Disner 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.

  PMID: 21731066 BACKGROUND

• Beck 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.

  PMID: 18628348 BACKGROUND

• Dolcos 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.

  PMID: 16481440 BACKGROUND

• Wolkenstein 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.

  PMID: 23219367 BACKGROUND

• Plewnia 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.

  PMID: 26360088 BACKGROUND

• Brunelin 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.

  PMID: 22581236 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Depressive Disorder, Major; Schizophrenia

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Frank Padberg, Prof. Dr.

  Ludwig-Maximilians-Universität München

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frank Padberg, Prof. Dr.

CONTACT

+40 (0)89 440053358; frank.padberg@med.uni-muenchen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. rer. biol. hum.

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 22, 2016
• Study Start: March 1, 2016
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2022
• Last Updated: June 2, 2020

Record last verified: 2020-05

Locations

DE (1)