Antenatal Depression
Conditions
Keywords
Non-invasive brain stimulation, tACS, Neurostimulation, Mood Disorders, Depression, Transcranial Alternating Current Stimulation, EEG, IAF-tACS, Individual Alpha Frequency tACS, Antenatal
Brief summary
The purpose of this pilot trial is to primarily assess safety, feasibility, and tolerability of PandA-tACS in antenatal depression and determine whether a single PandA-tACS session produces greater left dlPFC aperiodic slope flattening (reduction) from pre- to post-stimulation than IAF-tACS and sham.
Detailed description
The purpose of this study is to evaluate the safety, feasibility, tolerability, and brain effects of a single session of a personalized form of non-invasive brain stimulation called PandA-tACS in individuals with antenatal depression. PandA-tACS uses each participant's own EEG activity to create an individualized stimulation waveform. Participants will be females aged 18-45 years who are 14-32 weeks pregnant with a viable, low-risk singleton pregnancy and meet criteria for unipolar, non-psychotic major depressive disorder. Participants must be at low suicide risk, and be able to complete study procedures. Participants will complete screening, informed consent, clinical assessments, pregnancy safety review, and high-density EEG recordings. Eligible participants will attend one in-person stimulation visit and will be randomized to receive PandA-tACS, individualized alpha-frequency tACS, or sham stimulation. Stimulation will be delivered through scalp electrodes while participants are monitored by trained study staff. EEG, symptom ratings, blood pressure, pre-natal safety checks, and adverse event monitoring will be completed before and/or after stimulation. Optional MRI may be completed for electric-field modeling. Pregnancy and birth outcomes will be reviewed through the medical record.
Interventions
OTHERSham (placebo) tACS
Participants will be fitted with the same electrode setup and receive sham (placebo) tACS delivered using the neuroConn DC Stimulator MC.
OTHERIAF-tACS
Participants will be fitted with the same electrode setup and receive IAF-tACS delivered using the neuroConn DC Stimulator MC.
OTHERPandA-tACS
Participants will be fitted with the same electrode setup and receive PandA-tACS delivered using the neuroConn DC Stimulator MC.
Sponsors
University of North Carolina, Chapel Hill
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
After informed consent, participants, intervention staff, and outcome assessors will all be blind to participant allocation.
Intervention model description
Study design is a parallel arm design in which participants will be randomized 1:1:1 to receive PandA-tACS, IAF-tACS or sham (placebo)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18 - 45 * Capacity to understand all relevant risks and potential benefits of the study as determined by study staff (provision of informed consent) Stated willingness to comply with all study procedures and availability for the duration of the study * Low suicide risk (defined for this study as no active suicidal ideation in the past month and no suicide attempts, preparatory actions, or significant non-suicidal self-harm in the previous 2 years). Risk will be assessed utilizing the C-SSRS screen and triage version with further exploration of positive responses. * Between weeks 14-32 of viable singleton pregnancy * Currently meet DSM-5 criteria of unipolar, non-psychotic MDD which is confirmed by the DIAMOND * HDRS-17 score ≥8
Exclusion criteria
* DSM-5 diagnosis of severe alcohol use disorder (AUD) within the last 12 months, as evidenced by the DIAMOND * DSM-5 diagnosis of moderate to severe substance use disorder (excluding tobacco) within the last 12 months, as evidenced by the DIAMOND * Lifetime history of bipolar disorder, as evidenced by DIAMOND * Schizophrenia spectrum and other psychotic disorders, as evidenced by DIAMOND * History of autism spectrum disorder * Initiated any new psychotropic medication in the 6 weeks prior to screening or had a dose change or discontinuation in the preceding 6 weeks * Initiated a new course of psychotherapy in the 6 weeks preceding screening * Received any neurostimulation treatment in the 6 weeks preceding screening * History of seizures (excluding febrile seizures in childhood or Electroconvulsive Therapy (ECT) induced seizures) * Neurological disorders that would increase risk of participation or present a significant confounder in the opinion of the investigator (for example, dementia, history of stroke, Parkinson's disease, multiple sclerosis, history of traumatic brain injury with prolonged loss of consciousness, ruptured cerebral aneurysm, previous CNS radiation) * Previously failed to respond to ECT or transcranial magnetic stimulation (TMS) * Prior brain surgery and/or brain implants * Implanted medical device that uses electricity * Currently enrolled in another clinical trial for depression History of any of the following conditions: * Diabetes (gestational or general history) * Pre-term delivery (\<37 weeks) * Eclampsia * Pre-eclampsia with severe features * Asthma requiring daily medication * Chronic hypertension * Immune thrombocytopenia (ITP) * Hyperthyroidism requiring medication * Pre-pregnancy BMI 40 or more * In vitro fertilization (IVF) * Mullerian anomaly of uterus * Organ transplant * Prior history of deep vein thrombosis/pulmonary embolism (DVT/PE) or plan for anticoagulation during pregnancy * Fetus with autoimmune hydrops * Abnormal placenta Current pregnancy: * HIV/Hep B/Hep C with detectable viral loads * Anemia \[Hemoglobin under 11.0\] upon entry to pre-natal care * No scheduled pre-natal visits by 15 weeks * Placenta previa * Placenta accreta spectrum (PAS) * Pre-eclampsia * Gestational diabetes * Gestational hypertension * Fetus with abnormal chromosomes * Cervical length \< 2.5 cm * Presence of cerclage or vaginal progesterone to decrease chance of pre-term labor * Fetal growth restriction * Macrosomia * Polyhydramnios * Oligohydramnios * Rupture of membranes * Hyperemesis Gravidarum (HEG) * Confirmation testing for Tri 13/18/21 * Congenital anomalies on anatomy ultrasound that do not resolve with follow-up ultrasound
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety via the presence of any serious AEs | Day 1 to within 90 days of expected delivery date. | The number of serious adverse events (SAEs) deemed at least potentially related to PandA-tACS. |
| Tolerability of PandA-tACS | Immediately after intervention | Proportion of participants reporting stimulation intolerance or unable to complete stimulation due to tolerability. |
| Feasibility of PandA-tACS | Through completion of the study, roughly 2 years | Total number of enrolled participants. Must be at least 45 overall, and 15 per group. |
| Change in aperiodic slope in the dlPFC region. | Immediately before and after 40 minutes of stimulation (on single interventional session day). | Pre- to post-stimulation change in left dorsolateral prefrontal cortex (dlPFC) aperiodic slope (beta coefficient/exponent) derived from resting high-density (HD-EEG). The endpoint will be compared for PandA-tACS versus IAF-tACS and sham. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between modeled left dorsolateral prefrontal cortex (dlPFC) electric field strength and pre- to post-stimulation change in left dlPFC aperiodic slope | Immediately before and after 40 minutes of stimulation (on single interventional session day). | Within the PandA-tACS group, correlation between modeled left dlPFC electric field strength and pre- to post-stimulation change in left dlPFC aperiodic slope. |
Contacts
CONTACTFlavio Frohlich, PhD
CONTACTAthena Stein, PhD
PRINCIPAL_INVESTIGATORFlavio Frohlich, PhD
University of North Carolina, Chapel Hill
Outcome results
None listed