- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05523817
Targeting Specific Brain Networks to Treat Specific Symptoms in Depression
May 14, 2024 updated by: Mark C. Eldaief, MD, Massachusetts General Hospital
Probing the Functional and Behavioral Impact of Precision Circuit Modulation in Neuropsychiatric Diseases
Repetitive transcranial magnetic stimulation (rTMS) is a way of non-invasively stimulating specific brain networks and is an established treatment for Major Depressive Disorder (MDD).
This proposal will reveal network mechanisms of the therapeutic effects of rTMS by investigating how stimulating each network specifically changes network connectivity and behavior.
This will be done in a highly individualized manner in depressed and healthy patients, leading to more effective and more individualized treatments for depression.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
Network models are increasingly invoked to characterize the neurobiological underpinnings of mental illnesses.
Dysfunction within specific circuits promotes the formation of specific symptoms.
This suggests an opportunity to treat specific symptoms by modulating specific circuits.
Repetitive transcranial magnetic stimulation (rTMS) is capable of circuit-specific neuromodulation.
It is also an established treatment for Major Depressive Disorder (MDD).
Clinical experience suggests that rTMS treats different symptom constructs by stimulating different circuits.
However, there remains a critical lack of mechanistic evidence to support putative network mechanisms of rTMS, limiting its ability to treat patients with more personalized and optimized approaches.
This mechanistic proposal will first use resting-state functional connectivity (FC) MRI and customized analytic pipelines to characterize functional network topography in healthy and depressed individuals at high resolution.This data will be used to derive rTMS targets functionally situated in discrete prefrontal networks (e.g., control, default, salience, limbic/reward).
Next, patients will take part in a within-subject design in which they undergo rTMS to each target on separate days.
Each target will be stimulated four times on a given day, and after each stimulation changes will be measured with: (1) REST-BOLD MRI (to assess FC changes), (2) TASK-BOLD MRI (to assess changes in BOLD activation on paradigms validated to test RDoC constructs), (3) state-based questionnaires or (4) neuropsychological tests.
This work will facilitate individualized neuromodulation approaches based on network topography.
This will pollinate large-scale clinical trials assessing the effects of differential circuit modulation.
It will also illuminate circuit-construct relationships across neuropsychiatric disorders.
Study Type
Interventional
Enrollment (Estimated)
80
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02129
- Recruiting
- Massachusetts General Hospital
-
Contact:
- Mark Eldaief, MD
- Phone Number: 617-726-1728
- Email: meldaief@partners.org
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria for healthy participants:
- 18-65 years of age
- Capacity to provide informed consent form to participate in the study
Inclusion Criteria for participants with Major Depressive Disorder (MDD):
- 18-65 years of age
- Capacity to provide informed consent form to participate in the study
- Currently in a major depressive episode. Comorbid anxiety disorders and personality disorders will be allowed provided that MDD is the primary diagnosis.
Exclusion Criteria for all participants:
- Meeting criteria, in the past or currently, for bipolar affective disorder, hypomania or mania.
- Meeting criteria, in the past or currently, for a primary psychotic disorder (e.g., schizophrenia).
- Neurological conditions with known structural brain lesions, e.g., intracranial masses, multiple sclerosis.
- Any personal history of seizures or a family history of epilepsy in a first-degree relative.
- Metal in the body that is ferromagnetic or metallic injury to the eyes.
- Implanted pacemakers, medication pumps, vagal stimulators, deep brain stimulators, or ventriculoperitoneal shunts, etc.
- Substance abuse or dependence that is current and active within the last six months, as indicated by self-report (e.g., heroin, cocaine, methamphetamines).
- Inability to meet the safety criteria for MRI scanning for any other reason.
- Severe or unstable medical illness.
- Currently pregnant, as assessed with urine pregnancy test in women of childbearing age.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Non-Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: DLPFC Salience network target
iTBS delivered four times daily to an individually defined salience network representation in left dorsolateral prefrontal cortex (DLPFC).
|
iTBS is a form of non-invasive brain stimulation used to treat depression.
It works on the principles of electromagnetic induction.
Other Names:
|
Experimental: DLPFC Control network target
iTBS delivered four times daily to an individually defined control network representation in left dorsolateral prefrontal cortex (DLPFC).
|
iTBS is a form of non-invasive brain stimulation used to treat depression.
It works on the principles of electromagnetic induction.
Other Names:
|
Experimental: DLPFC Default network A target
iTBS delivered four times daily to an individually defined default network A representation in left dorsolateral prefrontal cortex (DLPFC).
|
iTBS is a form of non-invasive brain stimulation used to treat depression.
It works on the principles of electromagnetic induction.
Other Names:
|
Experimental: dmPFC Default network B target
iTBS delivered four times daily to an individually defined default network B representation in left dorsomedial prefrontal cortex (DMPFC).
|
iTBS is a form of non-invasive brain stimulation used to treat depression.
It works on the principles of electromagnetic induction.
Other Names:
|
Experimental: vmPFC limbic-reward network target
iTBS delivered four times daily to an individually defined reward network representation in left ventromedial prefrontal cortex (vMPFC).
|
iTBS is a form of non-invasive brain stimulation used to treat depression.
It works on the principles of electromagnetic induction.
Other Names:
|
Sham Comparator: SHAM stimulation
SHAM iTBS delivered four times daily to an individually defined SHAM region in left dorsolateral prefrontal cortex (DLPFC).
|
iTBS is a form of non-invasive brain stimulation used to treat depression.
It works on the principles of electromagnetic induction.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Resting-state functional connectivity (FC)
Time Frame: 1 hour
|
Changes in connectivity within and between brain networks
|
1 hour
|
Blood oxygenation level dependent (BOLD) activation
Time Frame: 1 hour
|
Changes in activation resulting from performing a specific functional MRI (fMRI) task
|
1 hour
|
Applied Cognition-General Concerns scale
Time Frame: 10 minutes
|
Subjects rate how statements about cognition and attention apply to them, e.g., "Thinking is foggy."
Score range is 8-40, with higher scores indicating lesser cognitive concerns.
|
10 minutes
|
Profile of Mood States Tension subscale
Time Frame: 5 minutes
|
Subjects are asked to rate how much certain adjectives about their mood apply to them at that moment, e.g., "tense", "nervous", "shaky."
Score range: 0-28, higher scores indicating more tension.
|
5 minutes
|
Profile of Mood States Vigor subscale
Time Frame: 5 minutes
|
Subjects rate how much mood adjectives apply to them at that moment, e.g., "full of pep," "energetic," "vigorous."
Score range 0-28, higher scores indicating more vigor.
|
5 minutes
|
Profile of Mood States Dejection subscale
Time Frame: 5 minutes
|
Subjects rate how much mood adjectives apply to them at that moment, e.g., "unworthy."
Score range 0-28, higher scores indicating higher dejection.
|
5 minutes
|
State Shame and Guilt Scale
Time Frame: 5-10 minutes
|
Subjects rate how much certain statements apply to them, e.g., "I feel regret."
Score range is 10-50, higher scores indicate more shame/guilt.
|
5-10 minutes
|
Fawcett-Clark Pleasure Capacity Scale
Time Frame: 5-10 minutes
|
Subjects anticipate how much they would enjoy a certain scenario, e.g., "you sit watching a beautiful sunset in an isolated part of the world."
Score range is 36 to 180, higher scores indicate higher pleasure capacity.
|
5-10 minutes
|
Digit-Span Test
Time Frame: 5 minutes
|
Subjects repeat number lists in forward or reverse order (maximum score is 8 forwards and 8 backwards, higher scores indicate better performance).
|
5 minutes
|
Tower of London Task
Time Frame: 5-10 minutes
|
Subjects plan a series of moves to match a start set to a goal set.
|
5-10 minutes
|
Delayed Match to Sample Task
Time Frame: 5 minutes
|
Subjects match patterns to a recently viewed sample pattern.
Score ranges from 0-30, with higher scores indicating better performance.
|
5 minutes
|
The Simon Test
Time Frame: 5 minutes
|
Subjects press different buttons based on incongruent spatial and/or color cues.
Scores range from 0-30, with higher scores indicating better performance.
|
5 minutes
|
Face-name Associative Paradigm
Time Frame: 30 minutes
|
Subjects must remember names paired with certain faces (DN-A).
Scores range from 0-32, with higher scores indicating better performance.
|
30 minutes
|
Reading the Mind Through the Eyes Test
Time Frame: 10 minutes
|
Subjects judge another person's mental state by looking at pictures of only their eyes.
Score ranges from 0-41, higher scores indicate better performance.
|
10 minutes
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Eldaief MC, Halko MA, Buckner RL, Pascual-Leone A. Transcranial magnetic stimulation modulates the brain's intrinsic activity in a frequency-dependent manner. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21229-34. doi: 10.1073/pnas.1113103109. Epub 2011 Dec 12.
- Fox MD, Halko MA, Eldaief MC, Pascual-Leone A. Measuring and manipulating brain connectivity with resting state functional connectivity magnetic resonance imaging (fcMRI) and transcranial magnetic stimulation (TMS). Neuroimage. 2012 Oct 1;62(4):2232-43. doi: 10.1016/j.neuroimage.2012.03.035. Epub 2012 Mar 19.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 12, 2024
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2028
Study Registration Dates
First Submitted
August 14, 2022
First Submitted That Met QC Criteria
August 30, 2022
First Posted (Actual)
August 31, 2022
Study Record Updates
Last Update Posted (Estimated)
May 15, 2024
Last Update Submitted That Met QC Criteria
May 14, 2024
Last Verified
May 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2022P002110
- 1R01MH129367-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
IPD Plan Description
This project will adhere to the NIH Grant Policy on Sharing of Unique Research Resources including the Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources.
The results of this research will be made available via publication in scientific journals and through scientific meetings where our findings are reported.
Publication of data shall occur during the project, if appropriate, or at the end of the project, consistent with normal scientific practices.
All publications will be made publicly available consistent with NIH policies.
Such research data will be redacted to prevent the disclosure of personal identifiers.
Drug and device information, study documents
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Major Depressive Disorder
-
Shalvata Mental Health CenterUnknownMAjor Depressive DisorderIsrael
-
York UniversityCentre for Addiction and Mental HealthSuspendedDisorder, Major DepressiveCanada
-
Seasons Biotechnology (Taizhou) Co., Ltd.CompletedMajor Depressive Disorder (MDDIndia
-
Gangnam Severance HospitalCompletedMajor Depressive Disorder(MDD)Korea, Republic of
-
University College, LondonCompletedUnipolar Major Depressive DisorderUnited Kingdom
-
Fundació Institut de Recerca de l'Hospital de la...Fondo de Investigacion SanitariaUnknown
-
Seasons Biotechnology (Taizhou) Co., Ltd.CompletedMajor Depressive Disorder (MDD)India
-
Repurposed Therapeutics, Inc.Unknown
-
GlaxoSmithKlineCompletedMajor Depressive Disorder (MDD)United States
-
AccexibleRecruitingMajor Depressive Disorder (MDD)Spain
Clinical Trials on Intermittent Theta Burst Stimulation (iTBS)
-
University of NottinghamRecruitingFeasibility of Neuromodulation With Connectivity-Guided iTBS for Cognitive Impairment in MS (TMS4MS)Multiple Sclerosis | Cognitive ImpairmentUnited Kingdom
-
The Hong Kong Polytechnic UniversityCompleted
-
VA Office of Research and DevelopmentNot yet recruitingSuicidal Ideation | Mild Traumatic Brain Injury | ImpulsivityUnited States
-
University of California, Los AngelesTerminated
-
King's College LondonSouth London and Maudsley NHS Foundation TrustWithdrawnBinge-Eating DisorderUnited Kingdom
-
Fabio FerrarelliNational Institute of Mental Health (NIMH)RecruitingSchizophreniaUnited States
-
Vastra Gotaland RegionUppsala University; Göteborg University; The Gothenburg Society of MedicineRecruiting
-
Stanford UniversityEnrolling by invitationTreatment Resistant DepressionUnited States
-
Jean-Marie AnnoniCompleted
-
Hôpital le VinatierTerminated