Deep-brain Magnetic Stimulation (DMS) in the Treatment of Major Depressive Disorder (DTMS)

The Effectiveness of Deep-brain Magnetic Stimulation in the Treatment of Major Depressive Disorder：a Preliminary Study

Transcranial magnetic stimulation (TMS) is an effective alternative for pharmacotherapy in major depressive disorder, but the effectiveness is not clear due to stimulated region, frequency and intensity of magnet field. Standard TMS techniques only can stimulate superficial cortical areas as the electric field decreases rapidly as a function of tissue depth，while depression is also interconnected with deeper neuronal regions. Deep-brain magnetic stimulation (DSM, or deep TMS, DTMS) allows stimulation of deeper cortical regions. Previous research has demonstrated that alpha frequency (8-13 Hz) EEG activity may have particular relevance to the response to antidepressants, and reduction of alpha frequency (8-13 Hz) could lead to negative symptoms. It has been reported that both alpha frequency and low-field magnetic stimulation could improve depressive symptoms.

The objective of this study is to compare the effectiveness of the two different parameters of DMS in the treatment of major depressive disorder. The changes of brain derived neurotropic factor (BDNF) are also investigated to make a relevant analysis of the improvement of depressive symptoms.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: High frequency stimulation; Device: Low frequency stimulation

Detailed Description

The study is designed as randomized, double-blinded, active-controlled trial in major depressive disorder.

Patients will be male or female, 18 to 60 years of age, right-handed, outpatient or inpatient status, with diagnosis of major depressive episode (single or recurrent) by DSM-IV. The HAMD-17 total score is no less than 18 at enrollment. The patients should be drug free at least 30 days before entering the trial. The eligible patients are randomized to one of the two treatment groups using a 1:1 ratio for the alpha frequency (high frequency) and 0.5Hz (low frequency) groups.

Throughout the course of the study, DMS sessions are administered by trained physicians for 20 minutes at a time, with 5 sessions per week, during 6 consecutive weeks. Raters who are blinded to the treatment arm perform evaluations. The effective outcome is assessed by the HAMD-17 and HAMA every two weeks including randomization. Serum BDNF level are also tested at each visits (Week 0, 2, 4 and 6). The safety in this study will be assessed by adverse event reporting, clinical laboratory measurements and physical examinations.

Primary efficacy measure will be assessed based on the decrease of HAMD-17 from randomization to endpoint (Week 6).

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100088
      • Beijing Anding Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has given written informed consent.
• Aged from 18 to 60 years old.
• Has a diagnosis of major depressive disorder by DSM-IV criteria.
• HAMD-17 ≥ 18.
• Right-handed.
• Be drug free at least 30 days at randomization.

Exclusion Criteria:

• Current Axis I primary psychiatric diagnosis other than major depressive disorder.
• Organic mental disease, including mental retardation.
• History of clinically significant disease, including any cardiovascular, hepatic, renal, respiratory, hematologic, endocrinologic, or neurologic disease, or clinically significant laboratory abnormality that is not stabilized or is anticipated to require treatment during the study.
• Subjects receiving an investigational agent (including different formulation and generic agents of investigational drug) in the previous 3 months prior to screening.
• Women in pregnancy or lactation, or female of child bearing potential without appropriate birth control measures.
• Has received ECT or MECT within 3 months prior to screening.
• Significant risk of suicidal and/or self-harm behaviors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High frequency stimulation; alpha burst, 8~12Hz, run 2 seconds, rest 8 seconds, lasts 20 minutes each time	Device: High frequency stimulation; The parameter of DMS: alpha frequency; Other Names: Alpha frequency stimulation
ACTIVE_COMPARATOR: Low frequency stimulation; 0.5Hz, run 0.5 seconds, rest 1.5 seconds, lasts 20 minutes each time	Device: Low frequency stimulation; The parameter of DMS: 0.5Hz; Other Names: 0.5Hz stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of Depression	the Change of 17-item Hamilton Depression Scale (HAMD-17) total score	From randomization to endpoint(Week 6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of Anxiety	the Change of Hamilton Anxiety Scale (HAMA) total score	From randomization to endpoint (Week 6)
Remission rate	The proportion of subjects at endpoint with HAMD-17≤7	From randomization to endpoint (Week 6)
Response rate	The proportion of subjects at endpoint with the reduction of HAMD-17 total score>=50%	From randomization to endpoint (Week 6)
Safety outcome 1	The incidence and nature of adverse events	From enrollment to endpoint (Week 6)
Safety outcome 2	The number of subject withdrawal due to adverse events	From randomization to endpoint (Week 6)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
BDNF change	Change of serum BDNF level	From randomization to endpoint (Week 6)

Collaborators and Investigators

• Sponsor: Capital Medical University

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (ACTUAL): January 1, 2011
• Study Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: June 30, 2014
• First Submitted That Met QC Criteria: July 3, 2014
• First Posted (ESTIMATE): July 9, 2014

Study Record Updates

• Last Update Posted (ACTUAL): August 31, 2017
• Last Update Submitted That Met QC Criteria: August 30, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Effectiveness; Brain derived neurotropic factor; Deep-brain magnetic stimulation
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: DMS-2010