Non-invasive Brain Stimulation in Subjects with Major Depressive Disorder (NIBS_tDCS)

Antidepressant and Related Neurophysiological Effects of Non-invasive Brain Stimulation in Subjects with Major Depressive Disorder

Introduction The study involves the recruitment of outpatients suffering from Major Depressive Disorder (MDD), diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Patients are on selective serotonin reuptake inhibitors (SSRIs) for at least 4 weeks and present residual depressive symptoms, defined by a score greater than 7 on the Hamilton Depression Rating Scale (HDRS-17).

Study Objectives

Primary Objective To investigate the effects of transcranial direct current stimulation (tDCS) on depressive symptoms in patients with depression, randomized into a "test" group and a "sham" group.

Secondary Objectives

To investigate the effects of tDCS on cognitive function in patients with depression, randomized into a "test" group and a "sham" group.

To evaluate changes in blood biomarkers, neurophysiological, and neurosonological variables after tDCS treatment in the same group of patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Major Depressive Disorder (MDD)
• Intervention / Treatment: Device: Active tDCS; Device: Sham treatment

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maria Salvina Signorelli, MD PhD; Phone Number: 3498127364; Email: maria.signorelli@unict.it
• Study Contact Backup: Name: Carmen Concerto, MD PhD; Email: c.concerto@policlinico.unict.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Patients with Major Depressive Disorder (MDD), as defined by the DSM-5-TR criteria;
• Presence of residual symptoms, defined by a Hamilton Depression Rating Scale score over 7;
• Age over 18 years.

Exclusion criteria:

• MMSE under 18 and/or CDR over 2;
• Other neurological diseases (stroke, multiple sclerosis, major head trauma, epilepsy) or psychiatric disorders other than those included (schizophrenia, bipolar disorder, etc.);
• Patients with severe clinical conditions, acute or uncontrolled chronic medical diseases;
• Endocrine diseases, vitamin deficiencies, or exposure to drugs associated with cognitive impairment and/or mood deflection;
• Alcohol abuse or recreational drug use;
• Contraindications to MRI and TMS (carriers of implanted devices, patients who have undergone craniotomy, presence of metal fragments or prostheses, history of epilepsy);
• Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: sham	Device: Sham treatment; The sham-tDCS intervention consist of a placebo 15 tDCS sessions distributed over 3 weeks (5 sessions per week, from Monday to Friday), at the same time each day, administered by the same operators and under identical experimental conditions. Each session last 30 minutes, with the Anode electrode placed on the left dorsal lateral prefrontal cortex (DLPFC) and the Cathode electrode on the right DLPFC. During the sessions only a 15-second initiation current is applied, providing the patient with the sensation of receiving an electric current on the scalp. Participants will also experience sounds and stimuli similar to those produced by active tDCS.
Experimental: active	Device: Active tDCS; The active tDCS protocol consist of 15 excitatory tDCS sessions distributed over 3 weeks (5 sessions per week, from Monday to Friday), at the same time each day, administered by the same operators and under identical experimental conditions. Each session last 30 minutes, with the Anode electrode placed on the left dorsal lateral prefrontal cortex (DLPFC) and the Cathode electrode on the right DLPFC at an intensity of 2 mA. The electrodes are positioned according to the 10-20 electroencephalography system (Anode on F3 and Cathode on F4).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Rating Scale - 17 (HDRS-17)	To investigate the effects of transcranial direct current stimulation (tDCS) treatment by administering Hamilton Depression Rating Scale - 17 (HDRS-17) on depressive symptoms in patients with depression, randomized into a "test" group and a "sham" group. Higher scores indicate greater severity of depressive symptoms, and thus a worse outcome. The minimum and maximum scores and their meaning are as follows: 0-7: No clinically significant depression; 8-13: mild depression; 14-18: moderate depression; 19-22: severe depression; 23-52: very severe depression.	From enrollment to the end of treatment at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montreal Cognitive Assessment (MOCA)	To investigate the effects of tDCS treatment on cognitive function in patients with depression, randomized into a "test" group and a "sham" group. Lower scores suggest greater cognitive impairment, while higher scores indicate better cognitive performance. Below are the minimum and maximum scores and their meaning: 30-26: normal cognitive function; 25-18: mild cognitive impairment; 17-10: moderate cognitive impairment; 9-0: severe cognitive impairment.	From enrollment to the end of treatment at 6 months
Frontal Assessment Battery (FAB)	To investigate the effects of tDCS treatment on cognitive function in patients with depression, randomized into a "test" group and a "sham" group. Specifically, FAB is a tool used to evaluate frontal lobe functions, such as executive functioning. Lower scores suggest greater impairment of frontal lobe functions, while higher scores indicate better functioning. Below are the minimum and maximum scores and their meaning: 18-15: normal frontal lobe functioning; 14-12: mild impairment; 11-9: moderate impairment; 9-0: severe impairment.	From enrollment to the end of treatment at 6 months
Apathy Evaluation Scale (AS)	To investigate the effects of tDCS treatment on cognitive function in patients with depression, randomized into a "test" group and a "sham" group. AS is a tool used to assess the presence of apathy in patients. Higher scores suggest greater severity of apathy, while lower scores indicate better motivation and engagement. Below are the minimum and maximum scores and their meaning: 18-27: no clinically significant apathy; 28-41: mild apathy; 42-55: moderate apathy; 56-72: severe apathy.	From enrollment to the end of treatment at 6 months
Stroop Color Test	To investigate the effects of tDCS treatment on cognitive function in patients with depression, randomized into a "test" group and a "sham" group. Stroop Color Test is a neuropsychological tool used to assess cognitive flexibility, selective attention and processing speed. Performance is assessed by comparing raw scores to normative data adjusted for age, education and cultural background. Minimum score (0) indicates no ability to perform the task; on the other hand, there is no universal maximum score. Tipically, performance is categorized into a normal range when it is consistent with age-matched norms; mild impairment when the performance is slightly below expectations for age or education; moderate to severe impairment when patient shows significant difficulty with cognitive control or selective attention.	From enrollment to the end of treatment at 6 months
To evaluate changes in blood biomarkers after tDCS treatment	A blood sample is collected at enrollment and after tDCS/sham treatment to evaluate biomarkers, including BDNF, NGF, VEGF, IGF1, Ang, Nrg1, IL-6, and TNFα. Concentrations will be reported in pg/mL or ng/mL, as appropriate for each biomarker.	From enrollment to the end of treatment at 6 months
To evaluate changes in cerebral hemodynamics after tDCS treatment	A transcranial Doppler (TCD) exam is conducted to assess cerebral hemodynamics. Parameters including VPS (cm/s), EDV (cm/s), MBFV (cm/s), PI (unitless), and RI (unitless) are recorded bilaterally from the middle cerebral arteries and the basilar artery, both at rest and after breath-holding tests. Measurements will be reported in their respective units (e.g., cm/s for velocities, unitless for indices).	From enrollment to the end of treatment at 6 months
To evaluate changes in Cortical Excitability Using TMS	Cortical excitability is evaluated using transcranial magnetic stimulation (TMS) with single- and double-pulse protocols. Parameters include: Resting motor threshold (rMT, % of maximum stimulator output); Cortical silent period (cSP, milliseconds); Motor evoked potential (MEP, µV); Paired-pulse stimulation (BiSTIM) is used to study inhibitory and excitatory circuits, including intracortical inhibition (ICI) and intracortical facilitation (ICF). Results are reported in their respective units (e.g., % stimulator output for rMT, ms for cSP, µV for MEP).	From enrollment to the end of treatment at 6 months

Collaborators and Investigators

• Sponsor: Carmen Concerto
• Investigators: Principal Investigator: Maria Salvina Signorelli, MD PhD, University of Catania

Study record dates

Study Major Dates

• Study Start (Estimated): January 2, 2025
• Primary Completion (Estimated): January 2, 2026
• Study Completion (Estimated): January 2, 2026

Study Registration Dates

• First Submitted: September 16, 2024
• First Submitted That Met QC Criteria: November 28, 2024
• First Posted (Actual): December 3, 2024

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: November 28, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: tDCS; Biomarkers; MD
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 130/2022/PO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No