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Brief, High-dose rTMS for Depression

Primary Purpose

Depression, Anxiety

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Repetitive Transcranial Magnetic Stimulation (rTMS)

About this trial

This is an interventional treatment trial for Depression

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

A negative urine pregnancy test, if female subject of childbearing potential.
Able to speak English and complete study forms, adhere to treatment regimens, and be willing to return for regular visits.
After full explanation of the study, willingness of participant is demonstrated by signing the informed consent form.

Exclusion Criteria:

Clinically unstable medical disease:
- cardiovascular
- renal
- gastrointestinal
- pulmonary
- metabolic
- endocrine
- other
CNS disease deemed progressive
Moderate or severe traumatic brain injury (TBI)
Pregnant females or those currently breast-feeding.
Current or history of schizophrenia or other psychotic disorder, except psychosis not otherwise specified (NOS) when the presence of sensory hallucinations is clearly related to the subject's trauma, Bipolar Type I disorder, or dementia:
- vascular
- Alzheimer's disease
- other types
Repeated abuse or dependence upon drugs (excluding nicotine and caffeine) within 6 days of study entry, with the exception of alcohol use disorder, which, at the discretion of the study team, may be permitted.

See further explanation under protection from risk.

Active participation or plan for enrollment in another evidence-based psychotherapeutic clinical trial
Participation in other psychotherapeutic modalities must have been stable for 3 months prior to enrollment and must remain stable throughout participation.
Currently taking medications that have short half-lives, lower the seizure threshold, and do not have evidence of antidepressant efficacy. These include:
- high dose theophylline or stimulants such as methylphenidate patients taking bupropion must be on a stable dose and take less than or equal to 300 mg/day. Stable means the same dose for 5 half-lives.
An implanted device in subject's head (shunt, cochlear implant) and/or metal in subject's head (other than dental implant).
History of seizures or a seizure disorder.

Sites / Locations

Medical University of South CarolinaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm Type

Experimental

Arm Label

Dose 1

Dose 2

Dose 3

Dose 4

Dose 5

Dose 6

Dose 7

Dose 8

Dose 9

Dose 10

Study 2: 10 Active Doses

Arm Description

All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 1 is five sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.

All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 2 is 10 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.

All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 3 is 15 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.

All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 4 is 20 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.

All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 5 is 20 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.

All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 6 is 25 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.

All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 7 is 30 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.

All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 8 is 35 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.

All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 9 is 40 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.

All participants will be randomized to one of 10 doses of accelerated rTMS. All doses are active and within established therapeutic levels of rTMS. Dose 10 is 40 sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.

All participants will be assigned to 10 sessions (per treatment day) of accelerated rTMS for 5 treatment days. All doses are active and within established therapeutic levels of rTMS. Dose 10 is 50 active sessions of 600 pulses at 120% of resting motor threshold. Intermittent theta burst triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 seconds.

Outcomes

Primary Outcome Measures

Depression severity (change in score)

Depression severity as assessed by: 1. Hamilton Scale for Depression (HAM-D) Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. 10 - 13 mild; 14-17 mild to moderate; >17 moderate to severe.

Depression severity (change in score)

Depression severity as assessed by: 2. Montgomery-Asberg Depression Rating Scale (MADRS) Rating lies on the defined scale steps (0, 2, 4, 6) or between them (1, 3, 5). Cut-off points include: 0 to 6 - symptom absent, 7 to 19 - mild depression, 30 to 34 - moderate, 35 to 60 - severe depression.

Depression severity (change in score)

Depression severity as assessed by: 3. Beck Depression Inventory-II (BDI-II) Rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63.

Secondary Outcome Measures

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Participants would complete various questionnaires (change in score assessed): 1. Inventory of Depression and Anxious Symptoms (IDAS-II) -Questions are rated on a scale from 1-5 and covers a wide array of psychological measures

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Participants would complete various questionnaires (change in score assessed): 2. Mood and Anxiety Symptom Questionnaire -Questions designed to assess symptoms of general distress using a 5-point Likert scale ranging from 1"not at all" to 5 "extremely".

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Participants would complete various questionnaires (change in score assessed): 3. Penn State Worry Questionnaire -Questions are rated on a scale from: 1-Not at all typical of me to 5-Very typical of me. Possible range of scores is 16-80 with the algorithm of Total scores: 16-39 Low Worry, 40-59 Moderate Worry, and 60-80 High Worry

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Participants would complete various questionnaires (change in score assessed): 4. PTSD Checklist (PCL-5) The PCL-5 is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. The PCL-5 has a variety of purposes, including: Monitoring symptom change during and after treatment Screening individuals for PTSD Making a provisional PTSD diagnosis -Questions are rated on a 5-point Likert scale (0 = "Not at all" to 4 = "Extremely")

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Participants would complete various questionnaires (change in score assessed): 5. Life Events Checklist (LEC-5) The Life Events Checklist for DSM-5 (LEC-5) is a self-report measure designed to screen for potentially traumatic events in a respondent's lifetime. The LEC-5 assesses exposure to 16 events known to potentially result in PTSD or distress and includes one additional item assessing any other extraordinarily stressful event not captured in the first 16 items. -Responses are as followed: Happened to me; Witnessed it; Learned about it; Part of my job; Not sure; Doesn't apply

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Participants would complete various questionnaires (change in score assessed): 6. Childhood Trauma Questionnaire -The Childhood Trauma Questionnaire is a brief survey of six early traumatic experiences (death, divorce, violence, sexual abuse, illness or other), and assesses individual's understanding of their childhood trauma.

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Participants would complete various questionnaires (change in score assessed): 7. Fagerstrom Test for Nicotine Dependence -Yes/no items are scored from 0 to 1 and multiple-choice items are scored from 0 to 3. The items are summed to yield a total score of 0-10. The higher the total Fagerström score, the more intense is the patient's physical dependence on nicotine.

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Participants would complete various questionnaires (change in score assessed): 8. Alcohol Use Disorders Identification Test (AUDIT) -The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item screening tool developed by the World Health Organization (WHO) to assess alcohol consumption, drinking behaviors, and alcohol-related problems.

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Participants would complete various questionnaires (change in score assessed): 9. World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) -Questions are rated on a a 5 point scale (from 0-4) Likert scale

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Participants would complete various questionnaires (change in score assessed): 10. World Health Organization Quality of Life - Brief Form (WHOQOL-BF) -Questions are rated on a a 5 point scale (from 1-5) Likert scale

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Participants would complete various questionnaires (change in score assessed): 11. Illness Intrusive Rating Scale (IIRS) -Questions are rated on a a 7 point scale (from 1-7) Likert scale which is a measure of the psychosocial impact of chronic disease

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Participants would complete various questionnaires (change in score assessed): 12. Quality of Life and Enjoyment and Satisfaction Questionnaire -Short Form (Q-LES-Q-SF) -Questions are rated on a 5 point scale (from 1-5) Likert scale. The minimum raw score on the Q-LES-Q-SF is 14, and the maximum score is 70.

Full Information

NCT ID

NCT04657432

First Posted

December 1, 2020

Last Updated

November 11, 2022

Sponsor

Medical University of South Carolina

Collaborators

National Alliance for Research on Schizophrenia & Depression

1. Study Identification

Unique Protocol Identification Number

NCT04657432

Brief Title

Brief, High-dose rTMS for Depression

Official Title

Accelerated Repetitive TMS for Affective Dysfunction: Establishing the Dose-Response Curve

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Recruiting

Study Start Date

May 25, 2021 (Actual)

Primary Completion Date

October 14, 2023 (Anticipated)

Study Completion Date

December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Medical University of South Carolina

Collaborators

National Alliance for Research on Schizophrenia & Depression

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

High frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to be safe, feasible, and acceptable. Conventionally, rTMS investigations have relied on rational decision trees for dosage determination. The purpose of this study is to systematically examine an accelerated protocol of intermittent theta burst (iTBS). Study 1 aims to provide a quantifiable dose-response curve for iTBS and depressive symptom reduction in major depression. Study 2 aims to determine the role of individual variations of their functional networks compared to the site of stimulation and clinical outcomes.

6. Conditions and Keywords

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

Depression, Anxiety

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Study 1: Participants will be randomized to 10 different doses of accelerated intermittent theta burst rTMS for remediation of depression symptoms. The goal is to determine the optimal dose in terms of efficacy while minimizing burden and side effects. Study 2: Participants will be assigned to 10 active sessions (per treatment day) of accelerated rTMS for 5 treatment days. All doses are active and within established therapeutic levels of rTMS. The goal is to determine the role of individual variations of their functional networks compared to the site of stimulation.

Masking

Participant

Masking Description

Study 1: All participants will be randomized to 10 different active doses of accelerated, intermittent theta burst rTMS.

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dose 1

Arm Type

Experimental

Arm Description

Arm Title

Dose 2

Arm Type

Experimental

Arm Description

Arm Title

Dose 3

Arm Type

Experimental

Arm Description

Arm Title

Dose 4

Arm Type

Experimental

Arm Description

Arm Title

Dose 5

Arm Type

Experimental

Arm Description

Arm Title

Dose 6

Arm Type

Experimental

Arm Description

Arm Title

Dose 7

Arm Type

Experimental

Arm Description

Arm Title

Dose 8

Arm Type

Experimental

Arm Description

Arm Title

Dose 9

Arm Type

Experimental

Arm Description

Arm Title

Dose 10

Arm Type

Experimental

Arm Description

Arm Title

Study 2: 10 Active Doses

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

Repetitive Transcranial Magnetic Stimulation (rTMS)

Intervention Description

MagVenture MagPro TMS System would be utilized to deliver 3-minute sessions of intermittent theta burst to left dorsolateral prefrontal cortex.

Primary Outcome Measure Information:

Title

Depression severity (change in score)

Description

Time Frame

Day 1, post-treatment point of 1 month

Title

Depression severity (change in score)

Description

Time Frame

Day 1, post-treatment point of 1 month

Title

Depression severity (change in score)

Description

Depression severity as assessed by: 3. Beck Depression Inventory-II (BDI-II) Rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63.

Time Frame

Day 1, post-treatment point of 1 month

Secondary Outcome Measure Information:

Title

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Description

Time Frame

Day 1, post-treatment point of 1 month

Title

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Description

Time Frame

Day 1, post-treatment point of 1 month

Title

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Description

Time Frame

Day 1, post-treatment point of 1 month

Title

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Description

Time Frame

Day 1, post-treatment point of 1 month

Title

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Description

Time Frame

Day 1, post-treatment point of 1 month

Title

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Description

Time Frame

Day 1, post-treatment point of 1 month

Title

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Description

Time Frame

Day 1, post-treatment point of 1 month

Title

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Description

Time Frame

Day 1, post-treatment point of 1 month

Title

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Description

Time Frame

Day 1, post-treatment point of 1 month

Title

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Description

Time Frame

Day 1, post-treatment point of 1 month

Title

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Description

Time Frame

Day 1, post-treatment point of 1 month

Title

Comorbid symptom severity, functional impairment, acceptability, and tolerability

Description

Time Frame

Day 1, post-treatment point of 1 month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: A negative urine pregnancy test, if female subject of childbearing potential. Able to speak English and complete study forms, adhere to treatment regimens, and be willing to return for regular visits. After full explanation of the study, willingness of participant is demonstrated by signing the informed consent form. Exclusion Criteria: Clinically unstable medical disease: cardiovascular renal gastrointestinal pulmonary metabolic endocrine other CNS disease deemed progressive Moderate or severe traumatic brain injury (TBI) Pregnant females or those currently breast-feeding. Current or history of schizophrenia or other psychotic disorder, except psychosis not otherwise specified (NOS) when the presence of sensory hallucinations is clearly related to the subject's trauma, Bipolar Type I disorder, or dementia: vascular Alzheimer's disease other types Repeated abuse or dependence upon drugs (excluding nicotine and caffeine) within 6 days of study entry, with the exception of alcohol use disorder, which, at the discretion of the study team, may be permitted. See further explanation under protection from risk. Active participation or plan for enrollment in another evidence-based psychotherapeutic clinical trial Participation in other psychotherapeutic modalities must have been stable for 3 months prior to enrollment and must remain stable throughout participation. Currently taking medications that have short half-lives, lower the seizure threshold, and do not have evidence of antidepressant efficacy. These include: high dose theophylline or stimulants such as methylphenidate patients taking bupropion must be on a stable dose and take less than or equal to 300 mg/day. Stable means the same dose for 5 half-lives. An implanted device in subject's head (shunt, cochlear implant) and/or metal in subject's head (other than dental implant). History of seizures or a seizure disorder.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Claire Cox, BA

Phone

(843)792-6282

coxcl@musc.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Lisa M McTeague, PhD

Phone

(843) 792-8274

mcteague@musc.edu

Facility Information:

Facility Name

Medical University of South Carolina

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lisa M McTeague, PhD

Phone

843-792-8274

mcteague@musc.edu

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Brief, High-dose rTMS for Depression

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