Transcranial Direct Current Stimulation in Major Depression
| Status: | Recruiting |
|---|---|
| Conditions: | Depression, Depression, Major Depression Disorder (MDD) |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 55 |
| Updated: | 6/16/2018 |
| Start Date: | February 2, 2018 |
| End Date: | July 31, 2022 |
| Contact: | Avery Garrett, BA |
| Email: | DGCNeurostimStudy@mednet.ucla.edu |
| Phone: | (424) 402-9051 |
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 intervention for reducing depressive
symptoms. We will investigate these questions in a two-part randomized double blind
exploratory clinical trial. The first part of the trial will compare how current flow and
functional imaging signal differs in the brain when using tDCS with more focal stimulation,
called high definition (HD) tDCS, compared to conventional tDCS (C-tDCS) or sham (non-active)
tDCS in patients with MDD.
Sixty people with depression (20 in each group) will be randomized to receive either HD-tDCS,
C-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 tDCS in the MRI scanner, which will allow us 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
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 intervention for reducing depressive
symptoms. We will investigate these questions in a two-part randomized double blind
exploratory clinical trial. The first part of the trial will compare how current flow and
functional imaging signal differs in the brain when using tDCS with more focal stimulation,
called high definition (HD) tDCS, compared to conventional tDCS (C-tDCS) or sham (non-active)
tDCS in patients with MDD.
Sixty people with depression (20 in each group) will be randomized to receive either HD-tDCS,
C-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 tDCS in the MRI scanner, which will allow us 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
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 we will test for the target engagement of the DLPFC and dACC by comparing
C-tDCS, HD-tDCS and sham tDCS applied to the left DLPFC in patients with moderate to severe
MDD before and after they complete 12 daily 20-minute sessions of C-tDCS, HD-tDCS or Sham
tDCS (n=20 randomized to each group). In-vivo electric current mapping performed at different
current intensities (0-2 mA) for 20-30 minutes, and change in regional cerebral blood flow
(rCBF) measured before and after a 12-day tDCS trial will determine acute and longer-term
modulation of DLPFC and dACC circuitry for each tDCS modality respectively.
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 we will test for the target engagement of the DLPFC and dACC by comparing
C-tDCS, HD-tDCS and sham tDCS applied to the left DLPFC in patients with moderate to severe
MDD before and after they complete 12 daily 20-minute sessions of C-tDCS, HD-tDCS or Sham
tDCS (n=20 randomized to each group). In-vivo electric current mapping performed at different
current intensities (0-2 mA) for 20-30 minutes, and change in regional cerebral blood flow
(rCBF) measured before and after a 12-day tDCS trial will determine acute and longer-term
modulation of DLPFC and dACC circuitry for each tDCS modality respectively.
Inclusion Criteria:
- Age between 18 to 55 years, inclusive
- Gender: all
- Race/ethnicity: all races and ethnic groups
- Capacity to provide informed consent
- Hamilton Rating Scale for Depression (HAMD) score of ≥14 and <24, with or without
symptoms of anxiety
- 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)
Exclusion Criteria:
- Pregnancy
- Non-English speaking
- Current Substance Use Disorder
- Neurological condition associated with brain abnormalities (e.g., traumatic brain
injury; recent stroke, tumor)
- Any contraindication to tDCS (e.g., skin disease or treatment causing irritation)
- Any condition that would contraindicate MRI scanning (metal implants, claustrophobia
or a breathing or movement disorder)
- Currently receiving any form of Cognitive Behavioral Therapy, Dialectical Behavioral
Therapy, or Acceptance and Commitment Therapy
- Change in antidepressant medication within 6-weeks of starting the trial
- Severe or treatment resistant depression - HAMD scores > 24 and a history of a major
depressive episode lasting >2-years or failure to 2 or more antidepressant trials in
the current index episode
- Any neuromodulation therapy (e.g., ECT, transcranial magnetic stimulation (rTMS),
tDCS) within the last 3-months
- Current or past (within the last 1-month) use of anticonvulsants, lithium,
psychostimulant, dexamphetamine
- Current use of decongestants or other medication including sleeping aids previously
shown to interfere with cortical excitability
- Schizophrenia Axis I disorder
- Dementia of any type
- Bipolar I disorder
- Diagnosis of seizure disorder or history of seizures
- Depression related to serious medical illness (i.e., mood disorder due to general
medical condition)
- Actively suicidal as defined by a score of 4 on item 3 of HAMD
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