Clinical trial NCT06979154: Pilot Study of Personalized Aperiodic Transcranial Alternating Current Stimulation in Antenatal Depression (PandA-tACS)
Official title: Pilot Study Using Endogenous Aperiodic Brain Activity to Personalize Transcranial Alternating Current Stimulation as a Treatment for Antenatal Depression: PandA-tACS
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Antenatal Depression
Major Depressive Disorder
Major Depressive Disorder in Pregnancy
Healthy Controls
Keywords: Behavioral Symptoms
Mood Disorders
Mental Disorders
Depression
Depressive Disorder
Major Depressive Disorder
Antenatal diagnoses
Prenatal diagnoses
Pregnancy
Electric Stimulation
non-invasive brain stimulation
transcranial alternating current stimulation
tACS
EEG
antenatal depression
Healthy Controls
Aperiodic brain activity
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Brain & Behavior Research Foundation
name: Michigan State University
First posted: 2025-05-18
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: First phase of study involves healthy controls. Second phase of study involves patients with antenatal depression.
Primary purpose: OTHER

Brief summary: The purpose of this study is to develop the safety, feasibility, and tolerability of a personalized transcranial alternating current stimulation (tACS) approach in antenatal depression.

Detailed description: The purpose of this study is an initial pilot study to develop the safety, feasibility, and tolerability of a novel, individualized transcranial alternating current stimulation (tACS) approach in antenatal depression, which delivers personalized stimulation waveforms based on the aperiodic component of individual participant EEG activity (PandA-tACS). In Phase I, five healthy controls will receive five consecutive days of PandA-tACS. High-density electroencephalography will be collected at baseline, Day 1, Day 5, and intermittently throughout stimulation sessions. A virtual follow-up will be completed two weeks following the final stimulation session. In Phase II, the PandA-tACS intervention will be expanded into five participants with antenatal depression, with the same study design. Additionally, depression, and related symptoms will be measured at Day 1, Day 5, at the two-week follow-up in these participants. Birth outcomes will be recorded within 90 days of expected delivery date as an additional form of safety monitoring.

Primary Aim: To investigate the safety, feasibility, and tolerability of five days of PandA-tACS in healthy controls (Phase I) and in participants with antenatal depression (Phase II).

Exploratory Aim: To investigate aperiodic EEG changes following five days of PandA-tACS in healthy controls and in participants with antenatal depression. Additionally, changes in depression symptoms will be investigated two weeks following PandA-tACS in antenatal depression.

Eligibility criteria: Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

* Female 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.

For healthy control population:

* Use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation, according to NIH Therapeutics Research Program Guidelines.

Additional for antenatal depression population:

* Between weeks 14-32 of viable singleton pregnancy
* Established obstetric care through UNC
* Pre-identified DSM-5 diagnosis of unipolar, non-psychotic MDD which is confirmed by the DIAMOND
* HDRS-17 score ≥14

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

* 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 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
* Unstable medical disorder or anything that would place the participant at increased risk or preclude the participant's full compliance with or completion of the study, in the opinion of the Investigator

Additional for the healthy control population:

* Current pregnancy or lactation (as determined by urine pregnancy test)
* History of depression, as evidenced by DIAMOND

Additional for the antenatal depression population:

* 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 prenatal care
  * No scheduled prenatal 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
* Other cause of markedly high-risk pregnancy as determined by the Investigator

Primary outcomes:
measure: Safety via the presence of any serious AEs related to stimulation
timeFrame: Day 1 to Follow-Up (Day 19) (HC) or Day 1 to end of monitoring (birth outcomes review within 90 days of expected delivery date) (antenatal depression)
measure: Feasibility via the number of participants enrolled relative to the target recruitment in each group
timeFrame: Baseline to end of recruitment period (12 months following recruitment start)
measure: Feasibility via the number of participants completing all study visits within the intervention and follow-up period
timeFrame: Baseline to Follow-Up (Day 19)
measure: Tolerability via the proportion of participants rating stimulation-related sensations as 'high'
timeFrame: Day 1 to Day 5
measure: Tolerability via the proportion of participants reporting intolerance to stimulation
timeFrame: Day 1 to Day 5
measure: Safety via review of birth outcomes within 90 days of birth in the antenatal depression population
timeFrame: Baseline to end of monitoring (birth outcomes review within 90 days of expected delivery date)
Secondary outcomes:
Other outcomes:
measure: Change in aperiodic exponent following the five-day PandA-tACS intervention
timeFrame: Day 1 to Day 5
measure: Change in HDRS-17 score following intervention in the antenatal depression population
timeFrame: Day 1 up to Follow-up (Day 19)
measure: Change in Edinburgh Postnatal Depression Scale (EPDS) in the antenatal depression population
timeFrame: Day 1 up to Follow-up (Day 19)
measure: Change in Snaith-Hamilton Pleasure Scale (SHAPS) in the antenatal depression population
timeFrame: Day 1 up to Follow-up (Day 19)
measure: Change in Clinical Global Impression Scale (CGI) in the antenatal depression population
timeFrame: Day 1 up to Follow-up (Day 19)
measure: Change in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) in the antenatal depression population
timeFrame: Day 1 up to Follow-up (Day 19)
Locations:
city: Chapel Hill
country: United States
facility: Carolina Center for Neurostimulation
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Flavio Frohlich, PhD, MSc ETH, MA
role: PRINCIPAL_INVESTIGATOR
References: