Concurrent fMRI-guided rTMS and Cognitive Therapy for the Treatment of Major Depressive Episodes

NCT03289923 | Completed

• 2 other identifiers: 17014717-M-0147
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Repetitive transcranial magnetic stimulation (rTMS) is a treatment for depression. It stimulates the brain. Researchers want to see if using magnetic resonance imaging (MRI) scans helps locate the best area for rTMS in each person. They also want to find other ways to make it more effective. Objective: To study the effects of combining MRI- guided transcranial magnetic stimulation (TMS) and talk therapy on the brain in people with depression. Eligibility: Adults ages 18-75 with a major depressive disorder and current depression. If taking an antidepressant, should have been doing so for at least 4 weeks. Design: Participants will be screened with medical and psychiatric history, psychiatric evaluation, physical exam, and blood and urine tests. Phase 1 is 1-4 visits in 1 week. Participants will have:

• Brain MRI. Participants will lie on a table in a scanner.
• Questions about their medical history and psychology symptoms
• Tests of mood and thinking
• Tests of brain activity. Participants may do tasks during these tests:
• A cone with magnetic detectors is put on the head.
• A cap with electrodes is put on the scalp.
• TMS. A brief electrical current passes through a wire coil on the scalp.
• A metal disk will be placed on the arm. A nerve will be stimulated with a small electrical shock. Phase 2 is about 6 to 7 weeks.
• There will be 30 daily sessions of combined therapy and repetitive TMS (rTMS) for 6 weeks.
• Participants will receive rTMS and another therapy by computer.
• For rTMS, repeated pulses will pass through the coil.
• This is followed by up to 3 additional visits, when:
• Participants will repeat Phase 1 tests
• Participants will rate their depression symptoms. Phase 3 is 3 visits over 3 months. Participants will rate their depression symptoms and repeat some of the previous questionnaires and tests of mood and thinking.

Conditions

Major Depressive Disorder

Keywords

Transcranial Magnetic Stimulation (TMS); Major Depressive Disorder; Cognitive Therapy

Outcome Measures

Primary Outcomes (1)

• Change in magnitude of Bold signal

  change in magnitude of BOLD signal with fMRI bold signal from DLPFC

  6 weeks after initiating intervention

Secondary Outcomes (2)

• Electrophysiological changes using MEG and EEG measures

  6 weeks after initiating intervention

• Clinical Rating Scales: BSL, C-SSRS, CTQ, HAM-A, NIH-BFI, PANAS, RBANS, RRS, SHAPS, and TLEQ,

  Variable: some 6 weeks after initiating intervention; others weekly

Study Arms (2)

Active TMS+ Cognitive Therapy

EXPERIMENTAL

active

Device: Active TMS + Cognitive therapy

Sham TMS + Cognitive Therapy

SHAM COMPARATOR

inactive

Device: Sham TMS + Cognitive therapy

Interventions

Sham TMS + Cognitive therapy DEVICE

Placebo Transcranial Magnetic Stimulation with cognitive therapy

Sham TMS + Cognitive Therapy

Active TMS + Cognitive therapy DEVICE

Active Transcranial Magnetic Stimulation with cognitive therapy.

Active TMS+ Cognitive Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 75 years of age.
• Use of effective method of birth control for women able to become pregnant
• English speaker
• Major Depressive Episode Diagnosis, and Severity:
• Subjects will meet the DSM-IV-TR primary diagnosis of initial or recurrent Major Depressive Disorder by DSM-IV-TR criteria
• HAM-D score \> 17 and Item 1 score greater than or equal to 2. Alternatively: At the initial screening and beginning of Phase II, subjects must have a baseline score on the MADRS \>= 20 and YMRS of \< 12.
• Current or past history of lack of response to at least one adequate antidepressant trial, operationally defined using the Antidepressant Treatment History Form (ATHF); a failed adequate trial of ECT would count as an adequate antidepressant trial (unless the ECT occurred within the last year, in which case the participant will be excluded).
• If currently on a stable dose of antidepressant medication, the dosage has been unchanged for at least four weeks prior to study entry. The medication must be continued, and at the same dosage throughout study participation.
• Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
• All subjects must have undergone a screening assessment under protocol 01-M-0254, The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers .
• Subjects are willing and able to adhere to the intensive treatment schedule and all required study visits.

You may not qualify if:

• Pregnant or nursing women or women who plan to become pregnant in the next 20 weeks while in the study.
• Persons who are able to get pregnant must be willing to use at least one form of effective birth control during the entire period of study participation (or until last clinical labs and rating) and have a negative pregnancy test at screening.
• Current or recent (within the past 6 months) diagnosis of substance abuse or dependence (excluding nicotine and caffeine)
• Past or current history of tinnitus
• Non English speaker
• Unable to understand or complete study tasks and instructions
• History of seizure except those therapeutically induced by ECT (childhood febrile seizures are acceptable and these subjects may be included in the study), history of epilepsy in self or first degree relatives, stroke, brain surgery, participants with history of any head trauma within 6 months of screening, or beyond 6 months prior to screening, history of head trauma with evidence of traumatic abnormality appearing on their brain scan, or with loss of consciousness \>5 min, or with other sequelae, excluding headache, lasting \> 24 hours will not be included in the study.
• Diagnosed with the following conditions (current unless otherwise stated):
• Any other current primary Axis I mood or psychotic disorder, including bipolar disorder, with the exception of most anxiety disorders (including generalized anxiety disorder (GAD), social anxiety disorder (also known as social phobia), specific phobia, panic disorder with and without agoraphobia, posttraumatic stress disorder (PTSD), anxiety secondary to medical condition, acute stress disorder (ASD)), although with obsessive-compulsive disorder (OCD) and substance-induced anxiety disorder excluded. While these anxiety disorders can be comorbid, they must be stable and the MDD must be the primary diagnosis.
• Depression secondary to a general medical condition, or substance-induced.
• Any bipolar disorder or psychotic disorder (lifetime), including schizoaffective disorder, or major depression with psychotic features in this or previous episodes.
• Eating disorder (current or within the past year).
• Obsessive compulsive disorder (lifetime).
• Subjects meeting criteria for Axis II cluster A or B diagnosis based upon DSM-IV TR criteria, which in the judgment of the Investigator may hinder the subjects in completing the procedures required by the study protocol.
• Subjects currently engaged or planning to engage in other treatment during the course of Phases I and II of the study (including behavior therapy, or other types of individual, family, or group psychotherapy/counseling), or subjects planning to start an antidepressant medication during the course of Phases I and II.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Carlos A Zarate, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: September 21, 2017
• Study Start: May 17, 2018
• Primary Completion: November 20, 2025
• Study Completion: November 20, 2025
• Last Updated: February 11, 2026

Record last verified: 2026-02

Locations

US (1)