Major Depressive DisorderNCT04507243
Transcranial Direct Current Stimulation (tDCS) Therapy in Major Depression
A study testing Active - HD tDCS in people with Major Depressive Disorder, run by University of California, Los Angeles at 1 site in United States.
Trial summary
Noninvasive transcranial direct current stimulation (tDCS) is a low-intensity neuromodulation technique of minimal risk that has been used as an experimental procedure for reducing depressive symptoms and symptoms of other brain disorders. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Active - HD tDCS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2020to 7 Mar 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Capacity to provide informed consent;
- Meet DSM-5 criteria for a moderate-to-severe MDE, with Hamilton Rating Scale for Depression (HAMD) score of ≥14 and <24;
- Treatment naïve or on a stable standard antidepressant regimen (including selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MOAIs) or tricyclic's (TCAs)) with no change in treatment 6-weeks prior to and during the tDCS intervention;
- Live within traveling distance to the University of California, Los Angeles (UCLA);
- Must refrain from making drastic hair-style changes throughout duration of study
Who cannot join
- Non-English speaking;
- Schizophrenia Axis I disorder;
- Primary anxiety disorder;
- Bipolar I disorder and psychotic disorders;
- Any neurological condition or major illness, including seizure disorder;
- Diagnosis of dementia of any type;
Show all 15Show fewer
- Co-morbid substance abuse in the last three months;
- Contraindications to MR scanning (including pregnancy);
- Contraindications to tDCS (e.g., skin disease or treatment causing irritation);
- Treatment-resistant depression, with a history of a major depressive episode lasting > 2 years or failure to 2 or more antidepressant trials in the current episode;
- Any neuromodulation therapy (e.g., ECT, rTMS, DBS, VNS, or tDCS) within the last 3 months;
- Active suicidality;
- Current or past (within the last 1-month) use of anticonvulsants, lithium, psychostimulants, or dexamphetamine;
- Current use of decongestants or other medication previously shown to interfere with cortical excitability;
- Currently receiving any form of Cognitive Behavioral Therapy, Dialectical Behavioral Therapy, or Acceptance and Commitment Therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Los Angeles (UCLA)
Los Angeles, California, 90095
About this study
Official title: Imaging-guided tDCS Therapy in Major Depression
Noninvasive transcranial direct current stimulation (tDCS) is a low-intensity neuromodulation technique of minimal risk that has been used as an experimental procedure for reducing depressive symptoms and symptoms of other brain disorders. Though tDCS applied to prefrontal brain areas is shown to reduce symptoms in some people with major depressive disorder (MDD), the extent of antidepressant response often differs. Methods that map current flow directly in the brain while a person is receiving tDCS and that determine how functional neuroimaging signal changes after a series of tDCS sessions may help us understand how tDCS works, how it can be optimized, and if it can be used as an effective antidepressant. Investigators will address these questions in a two-part randomized double blind exploratory clinical trial. For this part of the study, investigators will determine relationships between target engagement and clinical outcomes (mood) and functional sub-constructs of cognitive control and emotion negativity bias, and whether imaging markers at baseline predict changes in antidepressant response.
One hundred people with depression (50 in each group) will be randomized to receive either HD-tDCS or sham-tDCS for a total of 12 sessions each lasting 20 minutes occurring on consecutive weekdays. At the first and last session, subjects will receive 20-30 minutes of active or sham HD-tDCS in the MRI scanner, which will allow investigators to map tDCS currents, and track changes in regional cerebral blood flow (rCBF) pre-to- post treatment using completely non-invasive methods. At the first and last session and mid-way through the trial, participants will also complete a series of clinical ratings and neurocognitive tests.
Read the detailed description
Transcranial direct current stimulation (tDCS), a noninvasive neuromodulation technique, applied to the left dorsolateral prefrontal cortex (DLPFC) can reduce depressive symptoms and improve cognitive control in major depressive disorder (MDD). Such findings suggest modulation of top down prefrontal-limbic circuits, which are functionally distinct from ventro-limbic networks and include reciprocally connected DLPFC and dorsomedial anterior cingulate cortex (dACC). However, substantial variation in tDCS response is observed in MDD. This may be due to imprecise stimulation protocols and suboptimal engagement of the neural circuits mediating antidepressant response. Methods that optimize electrode placement and account for individual variation in anatomy and that map current flow directly in the brain may inform the mechanisms and potential clinical utility of tDCS. A new tDCS technique, high definition (HD) tDCS, offers more focal stimulation than conventional tDCS (C-tDCS). The degree to which C-tDCS or HD-tDCS engage dorsal prefrontal-limbic neural circuits is unknown, yet is vital for understanding, confirming and subsequently improving possible therapeutic effects. Innovative MRI techniques that are able to map tDCS currents in vivo and that track changes in regional cerebral blood flow occurring with tDCS over time can provide direct evidence of neural effects. Based on a) theoretical modeling of tDCS current flow, b) studies showing hypo-metabolism, decreased CBF or activity in dorsal prefrontal-limbic networks, c) modulation of these regions with treatment, and, c) our prior results showing significant relationships in between change in dACC rCBF and clinical response to electroconvulsive therapy (ECT), an established brain stimulation treatment, we will test for the tDCS engagement and modulation of the DLPFC and dACC using tDCS current mapping performed in vivo and perfusion MRI. MRI-guided neuronavigation will be used to optimize and standardize electrode placement for DLPFC stimulation.
In this trial, using HD-tDCS that optimal target engagement of DLPFC and larger rCBF changes in the DLPFC and dACC compared to C-tDCS in the first part of the trial, we will define relationships between target engagement and change in mood and behavior. Patients with moderate to severe MDD (N=100, n=50 in each group) will be randomized to Active or Sham left anodal DLPFC HD-tDCS. Patients will complete MRI scans including tDCS current mapping and pCASL as well as two functional imaging tasks probing cognitive control and emotion negativity bias, recruiting prefrontal-limbic circuitry, before and after completing a 12-day trial of 20-minute tDCS sessions.
- Conditions
- Major Depressive Disorder
- Being tested
- Active - HD tDCS, Sham - HD tDCS
- Keywords
- Transcranial direct current stimulation, MRI, Major Depression
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active - HD tDCSDevice
Non-invasive neuromodulation using HD electrodes placed on the scalp to deliver a constant, low current at 2 mA.
Sham - HD tDCSDevice
Sham neuromodulation using HD electrodes placed on the scalp to deliver a low current ramped up/down for 20 sec.
| Study group | Role | What they receive |
|---|---|---|
| Active - HD tDCS | Experimental | Participants randomized to this arm will receive 12 sessions of high definition tDCS (HD-tDCS) stimulation (Soterix Medical) delivered to the left dorsolateral prefrontal cortex for 20-30 minutes. Receives: Device: Active - HD tDCS |
| Sham - HD tDCS | Sham comparator | Participants randomized to this arm will receive 12 sessions of sham HD tDCS stimulation (Soterix Medical) delivered to the left dorsolateral prefrontal cortex for 20-30 minutes. Receives: Device: Sham - HD tDCS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measured joint longitudinal change in rCBF and mood scores over the tDCS trial
Correlation between percent change in rCBF after the tDCS trial and percent change in depressive symptoms for active versus sham tDCS conditions
Measured: 3 weeks
Secondary outcomes (2)
Measured joint longitudinal change in regional brain activation and mood scores over the tDCS trial
Correlation between percent change in regional brain activation for tasks probing cognitive control and emotion and percent change depressive symptoms for active versus sham tDCS conditions
Measured: 3 weeks
Measured magnetic fields and rCBF at baseline and change in mood scores over the tDCS trial
Correlation between variations in magnetic fields and rCBF at baseline and clinical outcomes at the end of the tDCS treatment trial
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2020
- Study start1 Dec 2020
- Primary completion7 Mar 2024
- Study completion7 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Active and Sham controlled
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Katherine Narr, University of California, Los Angeles
- Investigators
- Katherine L Narr, PhD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04507243
- Sponsor's protocol ID
- 20-001544
- Other IDs
- R33MH110526
- Status last verified
- Apr 2024
- First submitted
- 4 Aug 2020
- Last updated
- 30 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jog MA, Norris V, Pfeiffer P, Taraku B, Kozikowski S, Schneider J, Boucher M, Iacoboni M, Woods R, Narr K. Personalized High-Definition Transcranial Direct Current Stimulation for the Treatment of Depression: A Randomized Clinical Trial. JAMA Netw Open. 2025 Sep 2;8(9):e2531189. doi: 10.1001/jamanetworkopen.2025.31189.
PubMed 40932717
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging-guided tDCS Therapy in Major Depression
- ClinicalTrials.gov ID
- NCT04507243
- Acronym / sponsor ID
- 20-001544
- Conditions
- Major Depressive Disorder
- Keywords
- Transcranial direct current stimulation, MRI, Major Depression
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Mental Health (NIMH)
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 7 Mar 2024 (actual)
- Study completion
- 7 Mar 2024 (actual)
- First posted
- 11 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Noninvasive transcranial direct current stimulation (tDCS) is a low-intensity neuromodulation technique of minimal risk that has been used as an experimental procedure for reducing depressive symptoms and symptoms of other brain disorders. Though tDCS applied to prefrontal brain areas is shown to reduce symptoms in some people with major depressive disorder (MDD), the extent of antidepressant response often differs. Methods that map current flow directly in the brain while a person is receiving tDCS and that determine how functional neuroimaging signal changes after a series of tDCS sessions may help us understand how tDCS works, how it can be optimized, and if it can be used as an effective antidepressant. Investigators will address these questions in a two-part randomized double blind exploratory clinical trial. For this part of the study, investigators will determine relationships between target engagement and clinical outcomes (mood) and functional sub-constructs of cognitive control and emotion negativity bias, and whether imaging markers at baseline predict changes in antidepressant response.
One hundred people with depression (50 in each group) will be randomized to receive either HD-tDCS or sham-tDCS for a total of 12 sessions each lasting 20 minutes occurring on consecutive weekdays. At the first and last session, subjects will receive 20-30 minutes of active or sham HD-tDCS in the MRI scanner, which will allow investigators to map tDCS currents, and track changes in regional cerebral blood flow (rCBF) pre-to- post treatment using completely non-invasive methods. At the first and last session and mid-way through the trial, participants will also complete a series of clinical ratings and neurocognitive tests.
Detailed description
Transcranial direct current stimulation (tDCS), a noninvasive neuromodulation technique, applied to the left dorsolateral prefrontal cortex (DLPFC) can reduce depressive symptoms and improve cognitive control in major depressive disorder (MDD). Such findings suggest modulation of top down prefrontal-limbic circuits, which are functionally distinct from ventro-limbic networks and include reciprocally connected DLPFC and dorsomedial anterior cingulate cortex (dACC). However, substantial variation in tDCS response is observed in MDD. This may be due to imprecise stimulation protocols and suboptimal engagement of the neural circuits mediating antidepressant response. Methods that optimize electrode placement and account for individual variation in anatomy and that map current flow directly in the brain may inform the mechanisms and potential clinical utility of tDCS. A new tDCS technique, high definition (HD) tDCS, offers more focal stimulation than conventional tDCS (C-tDCS). The degree to which C-tDCS or HD-tDCS engage dorsal prefrontal-limbic neural circuits is unknown, yet is vital for understanding, confirming and subsequently improving possible therapeutic effects. Innovative MRI techniques that are able to map tDCS currents in vivo and that track changes in regional cerebral blood flow occurring with tDCS over time can provide direct evidence of neural effects. Based on a) theoretical modeling of tDCS current flow, b) studies showing hypo-metabolism, decreased CBF or activity in dorsal prefrontal-limbic networks, c) modulation of these regions with treatment, and, c) our prior results showing significant relationships in between change in dACC rCBF and clinical response to electroconvulsive therapy (ECT), an established brain stimulation treatment, we will test for the tDCS engagement and modulation of the DLPFC and dACC using tDCS current mapping performed in vivo and perfusion MRI. MRI-guided neuronavigation will be used to optimize and standardize electrode placement for DLPFC stimulation.
In this trial, using HD-tDCS that optimal target engagement of DLPFC and larger rCBF changes in the DLPFC and dACC compared to C-tDCS in the first part of the trial, we will define relationships between target engagement and change in mood and behavior. Patients with moderate to severe MDD (N=100, n=50 in each group) will be randomized to Active or Sham left anodal DLPFC HD-tDCS. Patients will complete MRI scans including tDCS current mapping and pCASL as well as two functional imaging tasks probing cognitive control and emotion negativity bias, recruiting prefrontal-limbic circuitry, before and after completing a 12-day trial of 20-minute tDCS sessions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Active and Sham controlled
| Arm | Type | Receives |
|---|---|---|
| Active - HD tDCS | Experimental | Device: Active - HD tDCSParticipants randomized to this arm will receive 12 sessions of high definition tDCS (HD-tDCS) stimulation (Soterix Medical) delivered to the left dorsolateral prefrontal cortex for 20-30 minutes. |
| Sham - HD tDCS | Sham comparator | Device: Sham - HD tDCSParticipants randomized to this arm will receive 12 sessions of sham HD tDCS stimulation (Soterix Medical) delivered to the left dorsolateral prefrontal cortex for 20-30 minutes. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Capacity to provide informed consent;
- Meet DSM-5 criteria for a moderate-to-severe MDE, with Hamilton Rating Scale for Depression (HAMD) score of ≥14 and <24;
- Treatment naïve or on a stable standard antidepressant regimen (including selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MOAIs) or tricyclic's (TCAs)) with no change in treatment 6-weeks prior to and during the tDCS intervention;
- Live within traveling distance to the University of California, Los Angeles (UCLA);
- Must refrain from making drastic hair-style changes throughout duration of study
Key exclusion criteria (15 listed)
- Non-English speaking;
- Schizophrenia Axis I disorder;
- Primary anxiety disorder;
- Bipolar I disorder and psychotic disorders;
- Any neurological condition or major illness, including seizure disorder;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active - HD tDCSNon-invasive neuromodulation using HD electrodes placed on the scalp to deliver a constant, low current at 2 mA. | Device | Active - HD tDCS |
| Sham - HD tDCSSham neuromodulation using HD electrodes placed on the scalp to deliver a low current ramped up/down for 20 sec. | Device | Sham - HD tDCS |
Primary outcome
Measured joint longitudinal change in rCBF and mood scores over the tDCS trial
Time frame: 3 weeks
Correlation between percent change in rCBF after the tDCS trial and percent change in depressive symptoms for active versus sham tDCS conditions
2 secondary outcomes
Measured joint longitudinal change in regional brain activation and mood scores over the tDCS trial
Time frame: 3 weeks
Measured magnetic fields and rCBF at baseline and change in mood scores over the tDCS trial
Time frame: 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2024.
- Derived from this study: PubMed 40932717Jog MA, Norris V, Pfeiffer P, Taraku B, Kozikowski S, Schneider J, Boucher M, Iacoboni M, Woods R, Narr K. Personalized High-Definition Transcranial Direct Current Stimulation for the Treatment of Depression: A Randomized Clinical Trial. JAMA Netw Open. 2025 Sep 2;8(9):e2531189. doi: 10.1001/jamanetworkopen.2025.31189.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katherine L Narr, PhD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active - HD tDCS in people with Major Depressive Disorder, run by University of California, Los Angeles at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measured joint longitudinal change in rCBF and mood scores over the tDCS trial (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04507243, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2024; AzTrials last refreshed its copy on 3 Nov 2026.