Clinical trial NCT06682689: Investigation of TVNS Administration on Postpartum Mental Health
Official title: Integrative Investigation of Transcutaneous Vagus Nerve Stimulation: Impact on Postpartum Mental Health Through Wearable Technology, Hormonal Analysis and Modulatory Factors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Postpartum Depression (PPD)
Postpartum Anxiety
Postpartum Sadness
Postpartum Blues
Keywords: tVNS
Transcutaneous vagus nerve stimulation
Postpartum
PPD
Depression
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
Collaborators: name: German Center for Mental Health (DZPG)
First posted: 2024-11-12
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The aim of the study is to explore whether transcutaneous vagus nerve stimulation (tVNS) may be effective in preventing mood swings and depressive symptoms in the postpartum phase, as well as serving as a supplementary intervention in cases where mood symptoms develop. The study will investigate the effects of tVNS intervention during the first 12 weeks postpartum. Pregnant women will be recruited for the study, and the intervention will begin shortly after giving birth. Participants will receive different instructions on how to use the tVNS device. Additional parameters such as physiological functions, chronic stress, hormones, environment, and personality traits will also be assessed.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* No malformation of fetal organs (no abnormalities detected during "organ screening").
* Ability to provide written consent for themselves.
* Sufficient German language skills to communicate and understand study procedures.

Exclusion Criteria:

* Exclusion criteria for tVNS use (i.e., pregnancy, active implants such as cochlear implants or cardiac pacemakers, cerebral shunts, skin problems, cardiovascular health issues).
* Cardiac arrhythmias or coronary heart disease.
* Neurological disorders.
* Current diagnosis or episode of a mood disorder.
* Diagnosed schizophrenia spectrum and other psychotic disorders.
* Severe substance use disorders.
* Individual exclusion may also occur based on other health issues if the study clinician determines that participation in the study may pose a disadvantage for the participant or the child.

Primary outcomes:
measure: tVNS-induced changes in postpartum depression symptoms
timeFrame: Measured during pregnancy (T1), 6 weeks after birth (T2), and 12 weeks after birth (T3)]
measure: tVNS-induced changes in the daily mood
timeFrame: From the recruitment through first 12 weeks of postpartum period
Secondary outcomes:
measure: Intervention acceptance analysis
timeFrame: through study completion, an average of 6 months
measure: Heart-rate variability changes
timeFrame: From the recruitment through first 12 weeks of postpartum period
measure: Subjective sleep quality changes
timeFrame: through study completion, an average of 6 months
measure: Objective sleep quality
timeFrame: through study completion, an average of 6 months
measure: Postpartum depression diagnosis (clinical threshold)
timeFrame: From the birth of the child to the end of the study (12 weeks)
measure: Objective measure of chronic stress
timeFrame: Two measurements: During pregnancy (T1) and 12 weeks postpartum (T3)
measure: Subjective chronic stress levels
timeFrame: Three times: During 1st visit, at 6 weeks postpartum and 12 weeks after birth
measure: Daily activity changes induced by tVNS
timeFrame: From the recruitment through first 12 weeks of postpartum period
Other outcomes:
Locations:
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen; Department of Psychiatry and Psychotherapy
state: BW
Study officials:
affiliation: University Hospital Tübingen
name: Birgit Derntl, Prof., PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Tübingen
name: Nils Kroemer, Prof., Dr. rer. nat.
role: PRINCIPAL_INVESTIGATOR
References: