In Vivo Cortical Excitability Modulation in Major Depressive Disorder (PDM-TMS)

February 21, 2024 updated by: Albino Maia, Fundacao Champalimaud
The pathophysiology of Major Depression Disorder (MDD) is unclear, with several theories for its neurobiological mechanisms. One possible explanation is the presence of altered neuroplasticity, which can be studied by Transcranial Magnetic Stimulation (TMS). Using TMS to study these mechanisms is performed by applying electromagnetic stimuli to the motor cortex, to obtain measures of temporary cortical excitability modulation. It is known that depressed patients with higher cortical modulation are more responsive to a TMS treatment course. However, it is unknown if there are differences in cortical modulation between depressed patients and healthy subjects. Our goal is to answer this question and contribute towards clarification of the neuroplasticity mechanisms underlying MDD. Accordingly, the investigators will access cortical excitability modulation measures in both depressed patients and healthy volunteers and compare their results. The investigators will also re-assess these measures after 6 weeks of antidepressant treatment. Finally, the investigators will study the association between cortical excitability measures and cognitive processes using an innovative cognitive task.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Study objectives

The aim of this study is to evaluate differences in the modulation of cortical excitability by a repetitive Transcranial Magnetic Stimulation (rTMS) protocol between patients with Major Depressive Disorder (MDD) and healthy people. The investigators hypothesize that patients with MDD exhibit less modulation of cortical excitability when compared to healthy people.

In order to accomplish this goal the investigators will:

  • Compare measures of cortical excitability between patients with MDD and healthy individuals;
  • Compare the degree of modulation of cortical excitability in motor cortex after the application of rTMS, between healthy individuals and patients with MDD;
  • Study the progression/evolution of these measures in the group of patients with MDD after 6 weeks of antidepressant treatment, while comparing patients that respond to treatment with patients with symptoms resistant to treatment;
  • Analyze the relationship between cortical excitability measures and cortical excitability modulation. Study participants will perform a psychophysical task, on a computer game, in order to evaluate certain cognitive processes and understand if there are differences in performance between patients with depression and healthy subjects.

Data Collection

  • Clinical assessment: Clinical interview will be performed with help of psychiatric, psychological and cognitive psychometric instruments (self-report questionnaires and structured interviews) to assess the participants' health.
  • Behavioural assessment: Participants will perform a psychophysical task in the form of a computer game.
  • Neurophysiological evaluation: protocol for assessing excitability and excitability modulation of the motor cortex by EMT and EMTr (ETBi).

Procedures

The participants recruited for the present project will be patients who are already being treated by health professionals at the Champalimaud Clinical Center, as well as healthy individuals, recruited from the nearby community. One cohort will include patients with active/symptomatic MDD and a second cohort will include patients with MDD in remission that are still in treatment. The third cohort will include a control group of healthy individuals. After they are referred to participate in this study, and if consent to participate is collected, they will be assessed to confirm their eligibility and group allocation will be performed. The study participants from all three observational groups will be submitted to (1) full clinical information assessment, (2) will be asked to perform a psychophysical task, i.e. a computer game. Finally, (3) the neurophysiological evaluation protocol will be applied. This neurophysiological evaluation protocol will be performed in two visits separated by at least 48h. This will make it possible to assess cortical excitability measures in both hemispheres independently and safely, allowing the acquisition of interhemispheric asymmetry measures. The order in which the cerebral hemispheres will be assessed will be randomized between participants. The first visit should take no longer than 120 minutes, and the second will last less than 45 minutes. Participants in the study will also be asked to come for a second study visit, to the Champalimaud Clinical Center, approximately 6 weeks after the first visit, the same study protocol will be repeated, in two consecutive sessions with the same procedures.Participants will not be rewarded monetarily; they will be supported for travel to the Clinical Center that may be necessary outside their individual clinical follow-up

Study Type

Observational

Enrollment (Estimated)

90

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

  • Portugal
      • Lisbon, Portugal, 1400-038
        • Recruiting
        • Champalimaud Foundation
        • Contact:
        • Principal Investigator:
          • Albino J Oliveira-Maia, MD, MPH, PhD
        • Sub-Investigator:
          • Gonçalo Cotovio, MD
        • Sub-Investigator:
          • Daniel Rodrigues da Silva, MSc
        • Sub-Investigator:
          • Francisco Faro Viano
        • Sub-Investigator:
          • Patricia Pereira, MSc
        • Sub-Investigator:
          • Carolina Seybert, PhD

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

Sampling Method

Probability Sample

Study Population

Participants in this study will be adults, aged 18 to 65 years, that will be recruited either for the clinical groups or healthy subjects group. The clinical population will include individuals with MDE diagnosis, and will be divided into two clinical groups:

  1. Patients in the acute phase of MDE, at the time they start a new antidepressant treatment (n≈30);
  2. Patients with symptomatic improvement, on continuation or maintenance antidepressant treatment (n≈30).

All groups, including healthy subjects, will be paired by age and sex.

Description

Inclusion criteria (clinical groups):

1. Diagnosis of major depressive episode or disorder as provided in the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) (American Psychiatric Association. 2013).

Exclusion criteria (clinical groups):

  1. Moderate to severe suicide risk;
  2. Known personal history of bipolar disorder or psychotic disorder;
  3. Alcohol or other substance abuse and/or dependence;
  4. Developmental disorder;
  5. Dementia;
  6. Presence of uncontrolled active medical illness;
  7. Known structural lesion of the central nervous system;
  8. Electrical or metallic brain implants;
  9. Cardiac implants;
  10. Epilepsy;
  11. Active use of medication known to cause seizures;
  12. Pregnancy;
  13. Breastfeeding.

For the healthy control group, participants will also be recruited at the Champalimaud Clinical Center, by advertisement in places of public circulation. The recruitment of this population will be done in order to generate a pairing with both clinical groups in terms of age and sex. The same exclusion criteria will be applied, as well as the presence of any history of neuropsychiatric disease. The total number of participants for this study will be approximately 90 volunteers. Exclusion criteria will be assessed through self-report and/or MINI.

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Current major depressive episode group
Adult individuals (18-65 yrs) diagnosed with current major depressive episode (MDE), under treatment or medication naif, starting a new antidperessant strategy (n≈30).
Other: No intervention/expousure
No interventions/expousure since this is an observational study.
Maintenance antidepressant treatment group
Adult individuals (18-65 yrs) previously diagnosed with major depressive episode (MDE) currently remitted under continuation or maintenance antidepressant treatment (n≈30).
Other: No intervention/expousure
No interventions/expousure since this is an observational study.
Healthy subjects group
Adult individuals (18-65 yrs) without current diagnosis of major neuropsychiatric disorders, inlcluding MDE, hence not under any antidepressant medication. The same exclusion criteria will be applied as in the two clincial groups.
Other: No intervention/expousure
No interventions/expousure since this is an observational study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Baseline left cortical excitability modulation
Time Frame: Baseline
Differences between groups in left cortical excitability modulation at baseline. Left cortical excitability modulation will be computed by assessing motor evoked potentials (MEP) before and after left-sided TMS modulation protocol.
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Left cortical excitability modulation changes according to treatment response
Time Frame: Baseline and after ~6 weeks.
Differences between responders and non responders to a new antidepressant treatment of left cortical excitability modulation changes between baseline and after 6 weeks.
Baseline and after ~6 weeks.

Collaborators and Investigators

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

Sponsor

Fundacao Champalimaud

Investigators

  • Principal Investigator: Albino J Oliveira-Maia, MD, MPH, PhD, Champalimaud Foundation

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

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)

May 19, 2020

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

June 28, 2022

First Submitted That Met QC Criteria

June 28, 2022

First Posted (Actual)

July 1, 2022

Study Record Updates

Last Update Posted (Actual)

February 23, 2024

Last Update Submitted That Met QC Criteria

February 21, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PDM-TMS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to make individual participant data (IPD) available to other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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