search
Back to results

The Effectiveness of rTMS in Depressed VA Patients

Primary Purpose

Major Depressive Disorder

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
rTMS
Sham Device
Sponsored by
VA Office of Research and Development
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring Mood Disorder, Depression, stress disorder, post-traumatic, Depressive Disorder, Stress Disorders, Traumatic, substance related disorders, Transcranial Magnetic Stimulation, repetitive, transcranial magnetic stimulation, Veterans, mental health

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Between 18 and 80 years of age
  • Using the Structured Clinical Interview for Diagnostic and Statistical Manual (DSM) Disorders (SCID) for DSM-IV-TR (First et al. 2002) patients will be diagnosed Major Depressive Disorder (MDD).
  • Have a Hamilton Rating Scale for Depression (HRSD-24) score greater or equal to 20 no more than 7 days prior to randomization.
  • Exhibit moderate level of resistance to antidepressant treatment defined, using the Antidepressant Treatment History Form (ATHF) (Sackeim et al. 1990), as failure of at least two adequate medication trials.
  • Duration of current episode of less than or equal to 10 years.
  • Ability to obtain a Motor Threshold (MT) (should be determined at the end of the screening process).
  • Currently under the care of a VA psychiatrist.
  • If on a psychotropic medication regimen, that regimen will be stable for at least 4 weeks prior to randomization and patient will be willing to remain on a stable regimen during the acute treatment phase.
  • Has an adequately stable condition and environment to enable attendance at scheduled clinic visits.

  • For female participants, agrees to use one of the following acceptable methods of birth control

    • Complete abstinence (not having sexual intercourse with anyone)
    • An oral contraceptive (birth control pills)
    • Norplant
    • Depo-Provera
    • A condom with spermicide
    • A cervical cap with spermicide
    • A diaphragm with spermicide
    • An Intrauterine device
    • Surgical sterilization (having tubes tied)
  • Able to read, verbalize understanding and voluntarily sign the Informed Consent Form prior to performance of any study-specific procedures or assessments.

Exclusion Criteria:

  • Pregnant or lactating female (This is an FDA-required exclusion. In the future, if rTMS becomes a proven treatment for major depression, its safety in the context of pregnancy should be studied separately (Nahas et al. 1999).
  • Unable to be safely withdrawn, at least two-weeks prior to treatment commencement, from medications that substantially increase the risk of having seizures. For the purpose of this study, those medications are listed in Appendix G (for example, theophylline).
  • Have a cardiac pacemaker.
  • Have an implanted device (deep brain stimulation) or metal in the brain.
  • Have a cochlear implant.
  • Have a mass lesion, cerebral infarct, increased intracranial pressure, or other active central nervous system (CNS) disease, including a seizure disorder.
  • Known current psychosis as determined by DSM-IV or SCID (axis I, psychotic disorder, schizophrenia) or a history of a non-mood psychotic disorder.
  • Known current Bipolar I disorder as determined by SCID or a History of Bipolar I disorder.
  • Current amnestic disorders, dementia, Blessed Orientation-Memory-Concentration (BOMC) greater than 10, delirium, or other cognitive disorders.
  • Current substance abuse (not including caffeine or nicotine) as determined by positive toxicology screen, or by history via SCID, within 3 months prior to screening.
  • Patients with an elevated risk of seizure due to traumatic brain injury (TBI).
  • Participation in another concurrent clinical trial.
  • Patients with prior exposure to rTMS.
  • Active current suicidal intent or plan as evidenced by a score of 4 or 5 on the suicidal ideation portion of the Columbia Suicide Severity Rating Scale (C-SSRS) or the endorsement of an actual attempt, interrupted attempt, or an aborted attempt in the past 6 months. All patients will be required to establish a written safety plan involving their primary psychiatrist and the treatment team before entering the clinical trial (See Section X.B.8).
  • Unstable cardiac disease or recent (< 3 months previous) myocardial infarction.
  • Patient refuses to sign consent for participation in the study.

Sites / Locations

  • VA Palo Alto Health Care System, Palo Alto, CA
  • San Francisco VA Medical Center, San Francisco, CA
  • Cincinnati VA Medical Center, Cincinnati, OH
  • Philadelphia VA Medical Center, Philadelphia, PA
  • VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
  • Ralph H. Johnson VA Medical Center, Charleston, SC
  • Central Texas Veterans Health Care System, Temple, TX
  • VA Salt Lake City Health Care System, Salt Lake City, UT
  • White River Junction VA Medical Center, White River Junction, VT

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Active rTMS

Sham rTMS

Arm Description

Those receiving experimental treatment will receive 20 to 30 sessions of rTMS in blocks of 5 sessions. The treatment will be delivered by trained medical personnel.

Those receiving the sham rTMS will receive 20 to 30 sessions of sham rTMS in blocks of 5 sessions. The treatment will be delivered by trained medical personnel.

Outcomes

Primary Outcome Measures

The Proportion of Participants Achieving Remission From Depression as Assessed by Hamilton Rating Scale for Depression
The primary outcome is a proportion of participants achieving remission from depression based on the HRSD24 less than or equal to 10 at the end of the acute treatment phase. 24 item Instrument with overall score range from 0 - 76. High values represent a worse outcome.

Secondary Outcome Measures

Mean Suicidal Ideation Score as Assessed by Beck Scale for Suicide Ideation (BSS)
To help clinicians screen psychiatric patients for suicidal ideation, the Beck Scale for Suicide Ideation was developed, and is herein referred to as the BSS. This self-report measure consists of 21 items with overall score range from 0 - 38, with the last two items not counted in scoring. A high score represents a worse outcome.
Mean Depression Score as Assessed by Beck Depression Inventory (BDI)
This measure is a 21-item self-report test presented in a multiple choice format which measures presence and extent of depression with overall score range from 0 - 63. A higher score represents a worse outcome. Each of the 21 items addresses a specific symptom or attitude that pertains to depressed patients, and which are consistent with descriptions of the depression within the peer-reviewed literature. While generally deemed less reliable than scales score by a trained rater (for example, the HRSD), the Beck scale is easy to administer, and provides convenient means by which patients can effectively communicate their own perception of their mood state.
Mean Mental Component Score as Assessed by VR-36 Mental Component Summary (MCS)
The VR-36 is a self-administered survey that measures eight dimensions of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these eight health domains, and two summary measures of physical and mental health: the Physical Component Summary (PCS) and Mental Component Summary (MCS). MCS is analyzed in this section. Standardized scoring ranging from 0-100. A higher score represents a better outcome.
Mean Physical Component Score as Assessed by VR-36 Physical Component Summary (PCS)
The VR-36 is a self-administered survey that measures eight dimensions of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these eight health domains, and two summary measures of physical and mental health: the Physical Component Summary (PCS) and Mental Component Summary (MCS). PCS is analyzed in this section. Standardized scoring ranging from 0-100. A higher score represents a better outcome.
Mean Depression Score as Assessed by the Montgomery Asberg Depression Rating Scale (MADRS)
As another measure of depression, the Montgomery-Asberg Depression Rating Scale (MADRS) has been used with increasing frequency in recent years to measure outcome in antidepressant efficacy trials. It offers an alternative view of depressive illness, and may be sensitive to depressive symptoms that are not easily captured in the context of the HRSD, such as hypersomnia, increased appetite, and concentration/indecision. The MADRS is a 10-item clinician rating of depressive symptoms. Each item is scored on a 7-point scale (0 to 6) (range 0-60). A high score represents a worse outcome.

Full Information

First Posted
August 26, 2010
Last Updated
February 8, 2018
Sponsor
VA Office of Research and Development
search

1. Study Identification

Unique Protocol Identification Number
NCT01191333
Brief Title
The Effectiveness of rTMS in Depressed VA Patients
Official Title
CSP #556 - The Effectiveness of rTMS in Depressed VA Patients
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
July 2, 2012 (Actual)
Primary Completion Date
February 15, 2017 (Actual)
Study Completion Date
March 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development

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.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this multi-site trial is to determine if repetitive Transcranial Magnetic Stimulation (rTMS) helps people with depression who have not been helped by medications or who have not been helped enough by medications.
Detailed Description
Major depression occurs in about 10% of American outpatients every year and of those, approximately 20% respond incompletely or not at all to trials of antidepressants, mood stabilizers, or psychotherapy (Kaplan and Sadock, 1996; Keller et al 1992; Thase, 2004). Treatment as usual for these cases of treatment resistant major depression (TRMD) frequently involves increased risks and increased side effects, such as those seen in monoamine oxidase inhibitors (MAOIs) and electroconvulsive therapy (ECT). New TRMD treatments are needed, preferably without major safety concerns or side effects as seen with aggressive polypharmacy or ECT. Repetitive transcranial magnetic stimulation (rTMS) is a method of delivering brain stimulation without the seizures or risks associated with ECT, nor the potential side effects and risks of MAOI therapy. Systematic review and meta-analysis of the studies to date, which are typically of a small scale, appear to show a positive effect in TRMD (Martin et al. 2003). With a minimal side effect profile, and the rarity of untoward events and side-effects (Pascual-Leone et al. 1993; Wassermann 1997), safety concerns regarding the use of rTMS are considerably less than with ECT. Given this, rTMS has the potential to be a significant advance in care, if it were shown to be effective in TRMD in VA patients. The trials of rTMS performed to date have not included participants with comorbid disorders, such as substance abuse and post-traumatic stress disorder (PTSD), thus the generalizability of their findings to a VA population is not clear. Further research including Veterans with possible comorbid disorders is necessary, given the high rates of co-occurring substance abuse and PTSD that is present in the Veteran population. The present study is a randomized, controlled trial that compares active rTMS to a sham condition in Veterans with treatment resistant major depression and possible comorbid post-traumatic stress disorder (PTSD) and / or a history of substance abuse. Veterans will remain under the care of their VA primary mental health provider throughout the project. Participants will be assessed at pre-, mid- and several post-treatment time points. This is a multisite trial that will be conducted at 9 VA Medical Centers around the country.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
Keywords
Mood Disorder, Depression, stress disorder, post-traumatic, Depressive Disorder, Stress Disorders, Traumatic, substance related disorders, Transcranial Magnetic Stimulation, repetitive, transcranial magnetic stimulation, Veterans, mental health

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
164 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active rTMS
Arm Type
Experimental
Arm Description
Those receiving experimental treatment will receive 20 to 30 sessions of rTMS in blocks of 5 sessions. The treatment will be delivered by trained medical personnel.
Arm Title
Sham rTMS
Arm Type
Placebo Comparator
Arm Description
Those receiving the sham rTMS will receive 20 to 30 sessions of sham rTMS in blocks of 5 sessions. The treatment will be delivered by trained medical personnel.
Intervention Type
Device
Intervention Name(s)
rTMS
Intervention Description
Repetitive Transcranial Magnetic Stimulation
Intervention Type
Device
Intervention Name(s)
Sham Device
Intervention Description
Placebo Device that simulates active rTMS treatment
Primary Outcome Measure Information:
Title
The Proportion of Participants Achieving Remission From Depression as Assessed by Hamilton Rating Scale for Depression
Description
The primary outcome is a proportion of participants achieving remission from depression based on the HRSD24 less than or equal to 10 at the end of the acute treatment phase. 24 item Instrument with overall score range from 0 - 76. High values represent a worse outcome.
Time Frame
End of acute treatment 4-6 weeks
Secondary Outcome Measure Information:
Title
Mean Suicidal Ideation Score as Assessed by Beck Scale for Suicide Ideation (BSS)
Description
To help clinicians screen psychiatric patients for suicidal ideation, the Beck Scale for Suicide Ideation was developed, and is herein referred to as the BSS. This self-report measure consists of 21 items with overall score range from 0 - 38, with the last two items not counted in scoring. A high score represents a worse outcome.
Time Frame
End of acute treatment 4-6 weeks, then end of F/U 6 months
Title
Mean Depression Score as Assessed by Beck Depression Inventory (BDI)
Description
This measure is a 21-item self-report test presented in a multiple choice format which measures presence and extent of depression with overall score range from 0 - 63. A higher score represents a worse outcome. Each of the 21 items addresses a specific symptom or attitude that pertains to depressed patients, and which are consistent with descriptions of the depression within the peer-reviewed literature. While generally deemed less reliable than scales score by a trained rater (for example, the HRSD), the Beck scale is easy to administer, and provides convenient means by which patients can effectively communicate their own perception of their mood state.
Time Frame
Baseline - end of acute treatment 4-6 weeks, then end of F/U 6 months
Title
Mean Mental Component Score as Assessed by VR-36 Mental Component Summary (MCS)
Description
The VR-36 is a self-administered survey that measures eight dimensions of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these eight health domains, and two summary measures of physical and mental health: the Physical Component Summary (PCS) and Mental Component Summary (MCS). MCS is analyzed in this section. Standardized scoring ranging from 0-100. A higher score represents a better outcome.
Time Frame
End of acute treatment 4-6 weeks, then end of F/U 6 months
Title
Mean Physical Component Score as Assessed by VR-36 Physical Component Summary (PCS)
Description
The VR-36 is a self-administered survey that measures eight dimensions of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these eight health domains, and two summary measures of physical and mental health: the Physical Component Summary (PCS) and Mental Component Summary (MCS). PCS is analyzed in this section. Standardized scoring ranging from 0-100. A higher score represents a better outcome.
Time Frame
End of acute treatment 4-6 weeks, then end of F/U 6 months
Title
Mean Depression Score as Assessed by the Montgomery Asberg Depression Rating Scale (MADRS)
Description
As another measure of depression, the Montgomery-Asberg Depression Rating Scale (MADRS) has been used with increasing frequency in recent years to measure outcome in antidepressant efficacy trials. It offers an alternative view of depressive illness, and may be sensitive to depressive symptoms that are not easily captured in the context of the HRSD, such as hypersomnia, increased appetite, and concentration/indecision. The MADRS is a 10-item clinician rating of depressive symptoms. Each item is scored on a 7-point scale (0 to 6) (range 0-60). A high score represents a worse outcome.
Time Frame
End of acute treatment 4-6 weeks, then end of F/U 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Between 18 and 80 years of age Using the Structured Clinical Interview for Diagnostic and Statistical Manual (DSM) Disorders (SCID) for DSM-IV-TR (First et al. 2002) patients will be diagnosed Major Depressive Disorder (MDD). Have a Hamilton Rating Scale for Depression (HRSD-24) score greater or equal to 20 no more than 7 days prior to randomization. Exhibit moderate level of resistance to antidepressant treatment defined, using the Antidepressant Treatment History Form (ATHF) (Sackeim et al. 1990), as failure of at least two adequate medication trials. Duration of current episode of less than or equal to 10 years. Ability to obtain a Motor Threshold (MT) (should be determined at the end of the screening process). Currently under the care of a VA psychiatrist. If on a psychotropic medication regimen, that regimen will be stable for at least 4 weeks prior to randomization and patient will be willing to remain on a stable regimen during the acute treatment phase. Has an adequately stable condition and environment to enable attendance at scheduled clinic visits. For female participants, agrees to use one of the following acceptable methods of birth control Complete abstinence (not having sexual intercourse with anyone) An oral contraceptive (birth control pills) Norplant Depo-Provera A condom with spermicide A cervical cap with spermicide A diaphragm with spermicide An Intrauterine device Surgical sterilization (having tubes tied) Able to read, verbalize understanding and voluntarily sign the Informed Consent Form prior to performance of any study-specific procedures or assessments. Exclusion Criteria: Pregnant or lactating female (This is an FDA-required exclusion. In the future, if rTMS becomes a proven treatment for major depression, its safety in the context of pregnancy should be studied separately (Nahas et al. 1999). Unable to be safely withdrawn, at least two-weeks prior to treatment commencement, from medications that substantially increase the risk of having seizures. For the purpose of this study, those medications are listed in Appendix G (for example, theophylline). Have a cardiac pacemaker. Have an implanted device (deep brain stimulation) or metal in the brain. Have a cochlear implant. Have a mass lesion, cerebral infarct, increased intracranial pressure, or other active central nervous system (CNS) disease, including a seizure disorder. Known current psychosis as determined by DSM-IV or SCID (axis I, psychotic disorder, schizophrenia) or a history of a non-mood psychotic disorder. Known current Bipolar I disorder as determined by SCID or a History of Bipolar I disorder. Current amnestic disorders, dementia, Blessed Orientation-Memory-Concentration (BOMC) greater than 10, delirium, or other cognitive disorders. Current substance abuse (not including caffeine or nicotine) as determined by positive toxicology screen, or by history via SCID, within 3 months prior to screening. Patients with an elevated risk of seizure due to traumatic brain injury (TBI). Participation in another concurrent clinical trial. Patients with prior exposure to rTMS. Active current suicidal intent or plan as evidenced by a score of 4 or 5 on the suicidal ideation portion of the Columbia Suicide Severity Rating Scale (C-SSRS) or the endorsement of an actual attempt, interrupted attempt, or an aborted attempt in the past 6 months. All patients will be required to establish a written safety plan involving their primary psychiatrist and the treatment team before entering the clinical trial (See Section X.B.8). Unstable cardiac disease or recent (< 3 months previous) myocardial infarction. Patient refuses to sign consent for participation in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jerome A. Yesavage, MD
Organizational Affiliation
VA Palo Alto Health Care System, Palo Alto, CA
Official's Role
Study Chair
Facility Information:
Facility Name
VA Palo Alto Health Care System, Palo Alto, CA
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304-1290
Country
United States
Facility Name
San Francisco VA Medical Center, San Francisco, CA
City
San Francisco
State/Province
California
ZIP/Postal Code
94121
Country
United States
Facility Name
Cincinnati VA Medical Center, Cincinnati, OH
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45220
Country
United States
Facility Name
Philadelphia VA Medical Center, Philadelphia, PA
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15240
Country
United States
Facility Name
Ralph H. Johnson VA Medical Center, Charleston, SC
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29401-5799
Country
United States
Facility Name
Central Texas Veterans Health Care System, Temple, TX
City
Temple
State/Province
Texas
ZIP/Postal Code
76504
Country
United States
Facility Name
VA Salt Lake City Health Care System, Salt Lake City, UT
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84148
Country
United States
Facility Name
White River Junction VA Medical Center, White River Junction, VT
City
White River Junction
State/Province
Vermont
ZIP/Postal Code
05009-0001
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28865495
Citation
Mi Z, Biswas K, Fairchild JK, Davis-Karim A, Phibbs CS, Forman SD, Thase M, Georgette G, Beale T, Pittman D, McNerney MW, Rosen A, Huang GD, George M, Noda A, Yesavage JA. Repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depression (TRMD) Veteran patients: study protocol for a randomized controlled trial. Trials. 2017 Sep 2;18(1):409. doi: 10.1186/s13063-017-2125-y.
Results Reference
background
PubMed Identifier
29955803
Citation
Yesavage JA, Fairchild JK, Mi Z, Biswas K, Davis-Karim A, Phibbs CS, Forman SD, Thase M, Williams LM, Etkin A, O'Hara R, Georgette G, Beale T, Huang GD, Noda A, George MS; VA Cooperative Studies Program Study Team. Effect of Repetitive Transcranial Magnetic Stimulation on Treatment-Resistant Major Depression in US Veterans: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Sep 1;75(9):884-893. doi: 10.1001/jamapsychiatry.2018.1483.
Results Reference
derived

Learn more about this trial

The Effectiveness of rTMS in Depressed VA Patients

We'll reach out to this number within 24 hrs