search
Back to results

Cortical rTMS as a Treatment for Depression

Primary Purpose

Major Depressive Disorder

Status
Enrolling by invitation
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Repetitive Transcranial Magnetic Stimulation
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Be male or female aged 18-60 years old
  • Meets MDD criteria
  • Has depressive symptoms according to the Patients Health Questionnaire (PHQ)-9 or Hamilton Depression Rating Scale (HDRS) or Snaith-Hamilton Pleasure Scale (SHAPS)
  • Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures
  • Female subjects must be non-nursing and not pregnant at the times of fMRI experiments and TMS treatment
  • Has no contraindications to MRI (pacemaker, cochlear implants, metal in eyes, other metal implants, etc.); Meets the pre- screening MRI questions provided by the Center for Advanced MR Imaging (CAMRI)
  • Has no contraindications to TMS (any types of non-removable metal in their head except the mouth, or within 12 inches of the coil, etc.); Meets the pre-screening TMS safety questionnaire (Transcranial Magnetic Stimulation Adult Safety Screen - TASS)

Exclusion Criteria:

  • In the opinion of the clinician and/or the research team, be expected to fail to complete the study protocol due to not tolerable to receive TMS
  • Unable to understand the design and requirements of the study
  • Unable to sign informed consent for any reason
  • Has an unstable medical condition, including AIDS, acute hepatitis, active TB, unstable cardiac disease, unstable diabetes, hepatic or renal insufficiency
  • Female subjects who are pregnant or nursing
  • Contraindications to MRI (pacemaker, cochlear implants, metal in the eye, other metal implants, etc.): Do not meet the pre-screening MRI questions provided by the CAMRI at BCM
  • Contraindications to TMS (any types of non-removable metal in their head except the mouth, or within 12 inches of the coil, etc.): Do not meet the pre-screening TMS safety questionnaire (TASS). Additional exclusion criteria for the TMS experiments are based on the recommendations described by the international consensus panel on brain stimulation.
  • Non-English speaking subjects (we do not have the staff and/or resources to include other language).

Sites / Locations

  • The Menninger Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

rTMS

Arm Description

20 sessions of rTMS

Outcomes

Primary Outcome Measures

Functional connectivity of orbital frontal cortex (OFC)
Functional connectivity of OFC changes after receiving TMS treatment
Outcome Changes in MDD subjects
The relationship between the functional connectivity changes and clinical outcome changes in MDD

Secondary Outcome Measures

Full Information

First Posted
June 27, 2022
Last Updated
June 14, 2023
Sponsor
Baylor College of Medicine
search

1. Study Identification

Unique Protocol Identification Number
NCT05487911
Brief Title
Cortical rTMS as a Treatment for Depression
Official Title
Cortical rTMS as a Treatment for Depression
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
June 14, 2023 (Anticipated)
Primary Completion Date
August 4, 2025 (Anticipated)
Study Completion Date
August 4, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Major depressive disorder (MDD) is a leading cause of disability worldwide with a 19% lifetime prevalence in the United States. Dysfunctional reward processing (e.g., the loss of pleasure) is one of the core features of MDD. Common treatments of MDD include psychological therapies (e.g., cognitive behavioral therapy), medication (e.g., bupropion, sertraline), and psychological therapies and medication combined, but they may not address the function of the reward circuit in MDD. These treatments often do not improve depressive symptoms in MDD patients who are classified as having treatment-resistant depression, and they may be unlikely to respond to further medication trials. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation that enables us to selectively excite or inhibit neural activity. Multiple TMS pulses given consecutively are known as repetitive TMS (rTMS), and the primary clinical location for applying rTMS is the left dorsolateral prefrontal cortex (dlPFC) for treatment of MDD. Many of these studies have shown that rTMS to the dlPFC may result in decreased depressive symptoms, but is only partially effective (response and remission rates of 41.2 and 35.3%, respectively). This evidence supports the importance of evaluating the efficacy of rTMS in other brain regions, such as the orbitofrontal cortex (OFC), in the treatment of MDD rather than in the dlPFC.
Detailed Description
The OFC is functionally connected to other cortical brain regions (e.g., prefrontal and parietal cortices) but also to subcortical areas in the dorsal striatum, a core reward circuitry region. The OFC is structurally connected to the medial forebrain bundle (MFB), deep brain stimulation (DBS) target for MDD, and the OFC may in fact be the mediator of anti-depressant effect. The functional connectivity between the OFC and those subcortical brain regions also plays an important role in addiction and suicide behaviors, which are MDD's most common comorbidities. Thus, it is clear that investigators need a better understanding of the therapeutic mechanisms using non-invasive brain stimulation (e.g., TMS) treatment to the OFC as applied to MDD patients. As such, the investigators propose to use a combination of interleaved TMS-fMRI, a novel method to observe and characterize causal manipulations of functional neural circuits, targeting the OFC and resting state fMRI to longitudinally study depressive symptoms and depression-related symptoms (e.g., addiction, suicidal behaviors) changes in MDD patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
MDD subjects enrolled will receive TMS
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
rTMS
Arm Type
Experimental
Arm Description
20 sessions of rTMS
Intervention Type
Device
Intervention Name(s)
Repetitive Transcranial Magnetic Stimulation
Intervention Description
4 weeks of active rTMS (total of up to 20 sessions)
Primary Outcome Measure Information:
Title
Functional connectivity of orbital frontal cortex (OFC)
Description
Functional connectivity of OFC changes after receiving TMS treatment
Time Frame
20 days
Title
Outcome Changes in MDD subjects
Description
The relationship between the functional connectivity changes and clinical outcome changes in MDD
Time Frame
20 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Be male or female aged 18-60 years old Meets MDD criteria Has depressive symptoms according to the Patients Health Questionnaire (PHQ)-9 or Hamilton Depression Rating Scale (HDRS) or Snaith-Hamilton Pleasure Scale (SHAPS) Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures Female subjects must be non-nursing and not pregnant at the times of fMRI experiments and TMS treatment Has no contraindications to MRI (pacemaker, cochlear implants, metal in eyes, other metal implants, etc.); Meets the pre- screening MRI questions provided by the Center for Advanced MR Imaging (CAMRI) Has no contraindications to TMS (any types of non-removable metal in their head except the mouth, or within 12 inches of the coil, etc.); Meets the pre-screening TMS safety questionnaire (Transcranial Magnetic Stimulation Adult Safety Screen - TASS) Exclusion Criteria: In the opinion of the clinician and/or the research team, be expected to fail to complete the study protocol due to not tolerable to receive TMS Unable to understand the design and requirements of the study Unable to sign informed consent for any reason Has an unstable medical condition, including AIDS, acute hepatitis, active TB, unstable cardiac disease, unstable diabetes, hepatic or renal insufficiency Female subjects who are pregnant or nursing Contraindications to MRI (pacemaker, cochlear implants, metal in the eye, other metal implants, etc.): Do not meet the pre-screening MRI questions provided by the CAMRI at BCM Contraindications to TMS (any types of non-removable metal in their head except the mouth, or within 12 inches of the coil, etc.): Do not meet the pre-screening TMS safety questionnaire (TASS). Additional exclusion criteria for the TMS experiments are based on the recommendations described by the international consensus panel on brain stimulation. Non-English speaking subjects (we do not have the staff and/or resources to include other language).
Facility Information:
Facility Name
The Menninger Clinic
City
Houston
State/Province
Texas
ZIP/Postal Code
77035
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23514317
Citation
Kessler RC, Bromet EJ. The epidemiology of depression across cultures. Annu Rev Public Health. 2013;34:119-38. doi: 10.1146/annurev-publhealth-031912-114409.
Results Reference
background
PubMed Identifier
26258159
Citation
Admon R, Pizzagalli DA. Dysfunctional Reward Processing in Depression. Curr Opin Psychol. 2015 Aug 1;4:114-118. doi: 10.1016/j.copsyc.2014.12.011.
Results Reference
background
PubMed Identifier
17073982
Citation
Forbes EE, Christopher May J, Siegle GJ, Ladouceur CD, Ryan ND, Carter CS, Birmaher B, Axelson DA, Dahl RE. Reward-related decision-making in pediatric major depressive disorder: an fMRI study. J Child Psychol Psychiatry. 2006 Oct;47(10):1031-40. doi: 10.1111/j.1469-7610.2006.01673.x.
Results Reference
background
PubMed Identifier
10446738
Citation
Nutt DJ. Care of depressed patients with anxiety symptoms. J Clin Psychiatry. 1999;60 Suppl 17:23-7; discussion 46-8.
Results Reference
background
PubMed Identifier
10333980
Citation
Horst WD, Preskorn SH. Mechanisms of action and clinical characteristics of three atypical antidepressants: venlafaxine, nefazodone, bupropion. J Affect Disord. 1998 Dec;51(3):237-54. doi: 10.1016/s0165-0327(98)00222-5.
Results Reference
background
PubMed Identifier
16554525
Citation
Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, Ritz L, Biggs MM, Warden D, Luther JF, Shores-Wilson K, Niederehe G, Fava M; STAR*D Study Team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006 Mar 23;354(12):1231-42. doi: 10.1056/NEJMoa052963.
Results Reference
background
PubMed Identifier
17640522
Citation
Hallett M. Transcranial magnetic stimulation: a primer. Neuron. 2007 Jul 19;55(2):187-99. doi: 10.1016/j.neuron.2007.06.026.
Results Reference
background

Learn more about this trial

Cortical rTMS as a Treatment for Depression

We'll reach out to this number within 24 hrs