In Vivo Cortical Excitability Modulation in Major Depressive Disorder

Major Depressive Disorder Clinical Trial

— PDM-TMS  

Official title:

In Vivo Cortical Excitability Modulation in Major Depressive Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05441969
• Other study ID #: PDM-TMS
• Status: Recruiting
• Start date: May 19, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: Fundacao Champalimaud
• Contact: Sofia Marques
• Phone: 00351 210480048
• Email: sofia.marques[@]research.fchampalimaud.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Other:
• No intervention/expousure
No interventions/expousure since this is an observational study.

Locations

Country	Name	City	State
Portugal	Champalimaud Foundation	Lisbon

Sponsors (1)

Lead Sponsor	Collaborator
Fundacao Champalimaud

Country where clinical trial is conducted

Portugal, 

References & Publications (33)

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* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Baseline left cortical excitability modulation	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	Left cortical excitability modulation changes according to treatment response	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.