Disorder-tailored Transcranial Direct Current Stimulation (tDCS) of the Prefrontal Cortex (MRSDC1)

May 29, 2020 updated by: Daniel Keeser, Ludwig-Maximilians - University of Munich

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: real tDCS
anode over electrode position F3, cathode over F4, 20 min, 2mA intensity
Device: Transcranial direct current stimulation (tDCS)
non-invasive electric brain stimulation method
SHAM_COMPARATOR: sham tDCS
frequency and duration correspondent active tDCS, ramp in and ramp out periods only without intermittent stimulation
Device: Transcranial direct current stimulation (tDCS)
non-invasive electric brain stimulation method

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
2 hours
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
2 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical trajectories
Time Frame: 8 weeks
Influence of observed online modulatory effects on clinical trajectories in patients
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ludwig-Maximilians - University of Munich

Investigators

  • Principal Investigator: Frank Padberg, Prof. Dr., Ludwig-Maximilians-Universität München

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 1, 2016

Primary Completion (ANTICIPATED)

January 1, 2021

Study Completion (ANTICIPATED)

January 1, 2022

Study Registration Dates

First Submitted

March 16, 2016

First Submitted That Met QC Criteria

March 16, 2016

First Posted (ESTIMATE)

March 22, 2016

Study Record Updates

Last Update Posted (ACTUAL)

June 2, 2020

Last Update Submitted That Met QC Criteria

May 29, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 493-14

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Schizophrenia

Clinical Trials on Transcranial direct current stimulation (tDCS)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Zimbabwe

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe