The study uses a crossover, repeated-measures, within-subject, and between-subject
placebo and active control design. Three groups of women who have recently given birth
will receive either high-intensity tVNS, low-intensity tVNS, or no stimulation
intervention for six weeks. After this period, the two tVNS groups will switch protocols
for another six weeks. Participants will also undergo a battery of psychometric and
neuropsychological tests at multiple time points. By applying a multilevel approach, the
investigators will assess changes in postpartum mood and mental state from subjective
(daily mood assessments, psychometric tests), cognitive (neuropsychological tests),
physiological (heart rate, sleep patterns), and endocrine (cortisol, sex hormones)
perspectives.
Throughout the study, all participants will answer app-based ecological momentary
assessments (EMA) to monitor mood fluctuations after stimulation and compare outcomes.
Participants' partners will be invited to take part in the study if they wish; they will
complete questionnaires regarding their mental health and the perceived support they
provide. During the initial screening, participants will receive detailed information
about the study, and inclusion and exclusion criteria will be evaluated.
At the first meeting (T1), informed broad consent will be obtained, and the study will be
explained in detail. Instructions for using the tVNS devices will be provided based on
group assignments. Participants will complete questionnaires, undergo a short
neuropsychological test, and provide hair samples for cortisol concentration analysis.
After giving birth, participants (or their partners, with permission) will notify the
researchers, and each woman in the experimental tVNS groups will receive a package
containing the stimulator and access to usage tutorials and instructions. All
participants will also receive smartwatches with usage instructions.
The main study will include 120 women who have recently given birth, randomly assigned to
one of three groups:
Group one (High-low tVNS) will first receive an active, high-intensity tVNS stimulation
protocol for six weeks at a self-chosen level below the pain threshold and will be
advised to use it for up to four hours a day (as per the device manual's full and maximal
stimulation session). Precise instructions and protocols to assess the stimulation
intensity will be given beforehand. After six weeks (T2), they will switch to the
low-intensity tVNS protocol used by group two.
Group two (Low-high tVNS) will use the device at the lowest possible intensity of 0,1
milliampere. This intensity equals the intensity of stimulation during the "OFF" Phase,
for more details see "Arms and interventions"". After six weeks, participants will switch
protocol for the one provided at the begging for group one for the remaining six weeks.
The device is pre-programmed to stimulate with constant parameters (except for
intensity), and to minimize placebo effects, participants will be informed that different
protocols with varying sensations are being tested.
Group three (No stimulation) will not receive any tVNS stimulation. Their mood and
symptoms will be assessed similarly to the other two groups, and physiological measures
will be monitored via smartwatch and hair sampling.
At week six (T2; around the 6th-7th week postpartum), participants from all groups will
visit the lab to complete questionnaires, provide hormone samples, and undergo
neuropsychological assessments.
During the experimental phase, participants will report daily on their current mood. They
will continue to complete repeated questionnaires assessing their mental health, quality
of life, sleep quality, and symptoms of depression and anxiety. At two postpartum time
points (T2 and T3; weeks 6 and 12 after parturition), participants will be asked to
return for additional sessions where blood will be drawn for hormonal analysis,
questionnaires will be repeated, and neuropsychological testing will be performed. At
week 12, hair samples will again be collected for cortisol concentration analysis.
A voluntary online follow-up is planned after the study. At 6 and 9 months postpartum,
participants will be invited to complete some of the standardised questionnaires,
previously administered earlier in the study. These questionnaires will assess various
aspects of their current state, including mental health, physical well-being, and
parenting stress
The study utilizes the CE-certified tVNS® E device to non-invasively stimulate the vagus
nerve, in compliance with European safety and performance standards (Class IIa, based on
(EU) 2017/745 for medical devices, classified as a short-term, active therapeutic,
non-invasive medical device under rule 9). This device stimulates the vagus nerve
non-surgically by targeting the auricular branch of the vagus nerve, which interfaces
with the skin at the cymba conchae of the external ear. The tVNS® E is approved for use
in healthy participants, as well as for the following conditions (without restrictions
for healthy participants, provided tVNS exclusion criteria are followed): treatment of
seizures in pharmaco-resistant epilepsy with focal and/or generalized seizures (to reduce
seizure frequency); adjunctive treatment of depression; treatment of emotional outbursts
in Prader-Willi syndrome (to reduce frequency); adjunctive treatment of chronic migraine
(to reduce headache frequency); and prophylactic migraine therapy for patients with
chronic migraines who refuse or do not tolerate prophylactic medication (tVNS® E
Instruction for Use, Version 1.6, 2023-01-30).
