Personalized aperiodic transcranial alternating current stimulation for depression during pregnancy

Pilot Study Using Endogenous Aperiodic Brain Activity to Personalize Transcranial Alternating Current Stimulation as a Treatment for Antenatal Depression: PandA-tACS

This pilot will test whether personalized aperiodic transcranial alternating current stimulation (PandA-tACS) delivered over five days is safe and tolerable for pregnant people with antenatal depression and for healthy volunteers.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 45 Years
• Sex: Female
• Sponsor: University of North Carolina, Chapel Hill (other)
• Drugs / interventions: radiation
• Locations: 1 site (Chapel Hill, North Carolina)
• Trial ID: NCT06979154 on ClinicalTrials.gov

What this trial studies

The trial delivers individualized tACS waveforms derived from each participant's EEG aperiodic component (PandA-tACS) across five consecutive daily sessions. In Phase I, five healthy controls receive the intervention with high-density EEG at baseline, day 1, day 5, and intermittently during sessions, plus a two-week follow-up. In Phase II, five pregnant participants with antenatal major depressive disorder undergo the same stimulation and EEG schedule with additional symptom assessments at day 1, day 5, two weeks post-intervention, and 4–6 weeks after delivery while birth outcomes are recorded for safety. The primary focus is safety, feasibility, and tolerability, with exploratory analyses of aperiodic EEG changes and symptom trajectories.

Who should consider this trial

Good fit: Ideal candidates are pregnant people aged 18–45 with antenatal major depressive disorder who have low suicide risk, can provide informed consent, and can attend five consecutive in-person stimulation sessions and follow-up visits.

Not a fit: People with active suicidal ideation or recent suicide attempts, significant psychiatric comorbidity, inability to attend daily clinic visits, or who do not meet the pregnancy/age criteria are unlikely to benefit from this small pilot.

Why it matters

Potential benefit: If successful, this approach could offer a short, non-pharmacologic brain-stimulation option to improve depressive symptoms during pregnancy.

How similar studies have performed: Personalized aperiodic tACS is a novel application with limited prior data, while other forms of noninvasive brain stimulation (tACS/tDCS) have shown mixed but sometimes promising results for 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 ≥8

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

Where this trial is running

Chapel Hill, North Carolina

• Carolina Center for Neurostimulation — Chapel Hill, North Carolina, United States (RECRUITING)

Study contacts

• Principal investigator: Flavio Frohlich, PhD, MSc ETH, MA — University of North Carolina, Chapel Hill
• Study coordinator: Athena Stein, PhD

Conditions: Antenatal Depression, Major Depressive Disorder, Major Depressive Disorder in Pregnancy, Healthy Controls, Behavioral Symptoms, Mood Disorders, Mental Disorders, Depression