Effects of Low-intensity Transcranial Magnetic Stimulation on Major Depressive Disorder, and on 5-hydroxyindoleacetic Acid and Brain-derived Neurotrophic Factor Levels

The goal of this randomised clinical trial is to evaluate the effects of transcranial magnetic stimulation (TMS) on major depressive disorder (MDD) and on the levels of 5-hydroxyindoleacetic acid (5-HIAA) and brain-derived neurotrophic factor (BDNF). TMS works to treat MDD by using low-intensity magnetic fields to modulate certain areas of the brain, activating them which can help improve the mood of those suffering from the disorder. Final metabolites of serotonin such as 5-HIAA and growth factors such as BDNF will also be studied before starting the intervention and at the end to check if there is a significant change in their concentration. Likewise, its safety will be evaluated by monitoring the symptoms that they present at the end of the intervention and one month later. The main questions that are intended to be answered are:

• Does low-intensity TMS reduce depressive symptoms in patients with MDD?
• Does low-intensity TMS significantly change the initial and final concentrations of 5-HIAA and BDNF?
• What adverse effects might patients who are exposed to low-intensity TMS experience? The researchers will compare low-intensity and accelerated TMS with sham TMS to see if low-intensity TMS works to treat MDD.

Participants:

• Will undergo an initial clinical assessment to confirm the disorder, comorbidities, and general health status.
• A 5 mL blood sample will be taken before starting the intervention.
• Low-intensity TMS will be applied for 4 days, 5 daily sessions of 200 s with 10-minute intersession intervals at a field intensity of 2-4 milliTesla (mT) and frequency of 50 Hz in theta bursts. Symptoms will be monitored daily.
• A 5 mL blood sample will be taken at the end of the intervention and general health status clinimetrics will be reapplied.

Study Overview

• Status: Recruiting
• Conditions: Transcranial Magnetic Stimulation; Placebo; Depression - Major Depressive Disorder
• Intervention / Treatment: Device: Low-intensity TMS; Device: Transcranial Magnetic Stimulation Sham

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Olga E Escobar Florez, Master of Medical Sciences; Phone Number: +524773703795; Email: oe.escobarflorez@ugto.mx
• Study Contact Backup: Name: Ma. Eugenia Garay Sevilla, Medical Sciences PhD; Phone Number: +524731414191; Email: marugaray_2000@yahoo.com

Study Locations

• Mexico
  • Guanajuato
    • León, Guanajuato, Mexico, 37328
      • Recruiting
      • High Specialty Medical Unit No. 1, Bajío. Mexican Social Security Institute
      • Contact: Olga E Escobar Florez, Master of Medical Sciences; Phone Number: +524773703795; Email: oe.escobarflorez@ugto.mx
      • Contact: Blanca O Murillo Ortíz, PhD Medical Sciences; Phone Number: 4772522013; Email: bomo907@hotmail.com
      • Principal Investigator: Blanca O Murillo Ortíz, PhD in medical sciences

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age between 18 and 60 years.
• Both sexes.
• Those who have a diagnosis of MDD previously made by the treating psychiatrist (considering time since diagnosis and recurrence of episodes).
• Those who continue with their respective treatment and attend follow-up consultations at the health facility.
• Those who do not have a history of epilepsy, schizophrenia, neurosurgeries.
• Those who do not have metal plates anywhere in the skull, neck, chest and shoulder.
• Those who do not use pacemakers.
• Those who do not take hormone substitutes.
• Those who agree to participate in the research.

Exclusion Criteria:

• Those who are pregnant.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-intensity TMS; This group will receive the real low-intensity TMS	Device: Low-intensity TMS; Low-intensity TMS will be applied for 4 days, 5 daily sessions of 200 s with 10-minute intersession intervals at a field intensity of 2-4 mT and frequency of 50 Hz in theta bursts.
Placebo Comparator: Sham low-intensity TMS; This group will receive the simulation of the low-intensity TMS	Device: Transcranial Magnetic Stimulation Sham; The control group will receive the simulation of low-intensity TMS without magnetic field induction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in symptoms of depression	Improvement in depression symptoms, assessed by the Hamilton Depression Rating Scale (HAM-D17) which measures the severity of depression symptoms.	From admission until the end of the 4 days of intervention and one month after the end of the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in serum concentrations of 5-HIAA and BDNF	5-HIAA and BDNF are neurochemical biomarkers that may correlate with response to depression treatment.	From admission until the end of the 4 days of intervention.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective changes in patient health	Evaluates the perception of patients' depressive symptoms using a self-assessment scale, complementing the primary measure	From admission until the end of the 4 days of intervention and one month after the end of the intervention
Changes in physical activity level	The International Physical Activity Questionnaire provides information about changes during the intervention week in the patient's physical activity intensity.	From admission until the end of the 4 days of intervention and one month after the end of the intervention
Changes in the Clinical Global Impression Scale (CGI)	CGI will help measure clinical changes globally.	From admission until the end of the 4 days of intervention.
Changes in sleep quality	It assesses sleep quality and detects possible improvements in sleep as an additional effect of low-intensity TMS, its improvement may indicate a secondary benefit of the treatment.	From admission and one month after the end of the intervention

Collaborators and Investigators

• Sponsor: Universidad de Guanajuato
• Collaborators: Instituto Mexicano del Seguro Social
• Investigators: Study Director: Ma. Eugenia Garay Sevilla, PhD in medical sciences, Universidad de Guanajuato; Study Director: José M De la Roca Chiapas, PhD in medical sciences, Universidad de Guanajuato; Study Director: Blanca O Murillo Ortíz, PhD in medical sciences, Universidad de Guanajuato; Study Chair: Angélica Hernández Rayas, Physics PhD, Universidad de Guanajuato; Principal Investigator: Olga E Escobar Florez, Master of Medical Sciences, Universidad de Guanajuato

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2024
• Primary Completion (Estimated): May 30, 2025
• Study Completion (Estimated): August 26, 2025

Study Registration Dates

• First Submitted: October 28, 2024
• First Submitted That Met QC Criteria: October 29, 2024
• First Posted (Actual): October 31, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2025
• Last Update Submitted That Met QC Criteria: May 5, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: depression; Major depressive disorder; brain-derived neurotrophic factor; 5-hydroxyindoleacetic acid; accelerated low-intensity transcranial magnetic stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: CEPIUG-P35-2023; R-2024-785-001 (Registry Identifier: National Committee for Scientific Research)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual Participant Data (IPD) information will not be shared to ensure the privacy and confidentiality of participants, sharing IPD could expose participants to additional risks of identification, for these reasons, and to protect the rights and confidentiality of participants, we have decided not to share IPD in this study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No