Clinical trial NCT06998368: A Causal Role for Voltage-gated Cav1.2 Calcium Channels in Mediating 5G FR1 Effects on Sleep-associated Brain Health in Humans
Official title: A Causal Role for Voltage-gated Cav1.2 Calcium Channels in Mediating 5G FR1 Effects on Sleep-associated Brain Health in Humans
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Mediation of 5G Effects on Sleep
Keywords: 5G
CACNA1C
CaV1.2
electromagnetic
EMF
nimodipine
RF-EMF
sleep
rs7304986
voltage-gated calcium channel
brain
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Federal Office for the Environment, Switzerland
First posted: 2025-05-31
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Each participant of the sleep study will undergo 4 experimental night recordings. On each of the experimental nights, one unique combination of two different interventions will be applied: active exposure to 5G RF-EMF or sham and administration of nimodipine (i.e. verum) or placebo.

The four combinations will be:

* placebo + sham exposure
* placebo + active exposure
* verum + sham exposure
* verum + active exposure. The sequence order of the 4 nights conditions will be randomized.
Primary purpose: BASIC_SCIENCE

Brief summary: Electromagnetic fields (EMFs) generated by the use of 5G technology influence certain sleep characteristics, especially in individuals carrying a specific genetic variant of a protein in the brain that regulates the activity of nerve cells. This protein is a voltage-gated calcium channel called CaV1.2 and could be involved in the effects of 5G technology on sleep. The calcium channel CaV1.2 can be selectively blocked by the drug nimodipine.

To demonstrate that CaV1.2 is indeed involved in the effects of 5G technology on sleep, the researchers are investigating in this study, with healthy subjects carrying the sought-after genetic variant, whether the administration of nimodipine and thus the blockade of the calcium channel before exposure mitigates or eliminates the effects of EMF on sleep health.

Detailed description: This study tests a causal role of voltage-gated CaV1.2 calcium channels in mediating the effects of a 5G electromagnetic field on sleep-related brain health in humans.

The study comprises a large-scale genetic screening in order to select the allele-carriers, a sleep screening night, and four experimental nights where participants are exposed to either an active 5G field or sham, combined with either nimodipine (which is a brain-penetrant L-type calcium channel blocker) or placebo. Participants will undergo polysomnographic recordings, high-density electroencephalography (EEG) during wake, peripheral measurements, cognitive and neuropsychiatric assessments.

Eligibility criteria: Inclusion Criteria:

For the first part of the study (genotyping and questionnaires):

* Age: 20-40 years old.
* German and/or English language skills (reading and writing)
* Informed Consent as documented by signature

For the second and third party of the study:

* Completion of the first part of the present study or of the precursor study (BASEC-ID: 2016-02049)
* CACNA1C rs7304986 T/C allele-carrier
* Male gender
* Female gender if using hormonal contraception for the duration of the study (e.g., pill as combination/single preparation, three-month injection, hormonal IUD, hormonal implant, hormonal patch)
* Right-handedness
* Body Mass Index (BMI): BMI comprised between 17.0 kg/m2 and 26.0 kg/m2

  * Moderate alcohol consumption (less than 5 reported alcoholic drinks per week)
  * Moderate caffeine consumption (less than 3 reported caffeinated beverage or food products per day such as cola, coffee, energy drinks, green and black tea, chocolate)
  * Informed Consent as documented by signature.

Exclusion Criteria:

For the second and third party of the study:

* Travel with a time difference of more than 2 time zones in the last 30 days before study entry or during the study period
* Shift work at night
* Extreme chronotype or duration of sleep (5 hours \< reported habitual sleep duration per night \> 10 hours)
* Known sleep disorders or diseases
* Serious acute or chronic neurological, mental, or general medical conditions that, in the opinion of the investigator, may pose a risk to participation or affect study measurements
* Use of medications (regularly or during the study period) that, in the opinion of the investigator, may affect study measurements.
* Use of illegal drugs
* Smoking (or other tobacco use)
* Known or suspected non-compliance with the investigators' indications
* Inability to follow the procedures of the study, e.g., due to language problems, psychological disorders, dementia, etc.
* Severe skin allergies or hypersensitivities
* Participation in another clinical trial in the last 30 days prior to inclusion or during the present study
* Contraindications to nimodipine, e.g., known hypersensitivity or allergy to nimodipine or any of the excipients
* Other cases in which the use of nimodipine is discouraged according to the summary of product characteristics (SPC)
* Women who are pregnant or breast feeding
* Intention to become pregnant during the course of the study
* Lack of safe contraception, defined as: female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases (Note: Female participants who are surgically sterilized / hysterectomized or post-menopausal for longer than 2 years are not considered as being of child bearing potential)
* Sleep apnea and nocturnal myoclonus index of ≥ 5 per hour of sleep (as assessed during the screening night)
* Sleep efficiency \< 80% (as assessed during the screening night)
* Other relevant findings in the screening/adaptation night (e.g., indications of sleep disorders), which in the opinion of the investigator may pose a risk for participation or influence the study measurements.

Primary outcomes:
measure: Sleep spindle center frequency
timeFrame: Assessed on each of the four experimental nights, from overnight electroencephalographic recordings following randomized combinations of drug (nimodipine or placebo) and RF-EMF exposure (5G or sham), with a minimum of 3 days washout between sessions
Secondary outcomes:
measure: Sex distribution of participants
timeFrame: At the large-scale genetic screening
measure: Age of Participants
timeFrame: At the large-scale genetic screening
measure: Pregnancy status
timeFrame: At the large-scale genetic screening
measure: EEG power spectra during Non-Rapid-Eye-Movement (NREM) sleep
timeFrame: Assessed on each of the four experimental nights, from overnight electroencephalographic recordings following randomized combinations of drug (nimodipine or placebo) and RF-EMF exposure (5G or sham), with a minimum of 3 days washout between sessions
measure: Total sleep time
timeFrame: Assessed on each of the four experimental nights, from overnight electroencephalographic recordings following randomized combinations of drug (nimodipine or placebo) and RF-EMF exposure (5G or sham), with a minimum of 3 days washout between sessions
measure: Neurocognitive performance as assessed in the psychomotor vigilance task (PVT)
timeFrame: Assessed on each of the four experimental nights, pre- and post-sleep
measure: Heart rate
timeFrame: Assessed on each of the four experimental nights, from electrocardiographic recordings during pre-sleep exposure and polysomnographic overnight recordings
measure: Handedness of participants
timeFrame: At the large-scale genetic screening
measure: BMI of participants
timeFrame: At the large-scale genetic screening
measure: Highest level of education of participants
timeFrame: At the large-scale genetic screening
measure: Phone call time
timeFrame: At the large-scale genetic screening
measure: Caffeine consumption
timeFrame: At the large-scale genetic screening
measure: Alcohol consumption
timeFrame: At the large-scale genetic screening
measure: Electrohypersensitivity (EHS) status
timeFrame: At the large-scale genetic screening
measure: Sleep disturbances
timeFrame: At the large-scale genetic screening
measure: Comorbidities
timeFrame: At the large-scale genetic screening
measure: Night-shift work
timeFrame: At the large-scale genetic screening
measure: Use of medications
timeFrame: At the large-scale genetic screening
measure: Use of illegal drugs
timeFrame: At the large-scale genetic screening
measure: Use of tobacco products
timeFrame: At the large-scale genetic screening
measure: Subjective sleep quality
timeFrame: At the large-scale genetic screening
measure: Daytime sleepiness
timeFrame: At the large-scale genetic screening
measure: Diurnal preference
timeFrame: At the large-scale genetic screening
measure: Habitual bedtime
timeFrame: At the large-scale genetic screening
measure: Habitual rise time
timeFrame: At the large-scale genetic screening
measure: Reported time to fall asleep
timeFrame: At the large-scale genetic screening
measure: Reported sleep duration
timeFrame: At the large-scale genetic screening
measure: Positive and Negative Affect Schedule
timeFrame: At the large-scale genetic screening
measure: Nocturnal mentation
timeFrame: At the large-scale genetic screening
measure: Depressive tendency
timeFrame: At the large-scale genetic screening
measure: Mental suggestibility tendency
timeFrame: At the large-scale genetic screening
measure: Schizotypal tendency
timeFrame: At the large-scale genetic screening
measure: ADHD tendency
timeFrame: At the large-scale genetic screening
measure: EEG power spectra during wakefulness
timeFrame: Assessed on each of the four experimental nights, from pre- and post-sleep wake electroencephalographic recordings
measure: EEG power spectra during Rapid Eye Movement (REM) sleep
timeFrame: Assessed on each of the four experimental nights, from overnight electroencephalographic recordings following randomized combinations of drug (nimodipine or placebo) and RF-EMF exposure (5G or sham), with a minimum of 3 days washout between sessions
measure: Aperiodic component of the EEG power spectrum during NREM sleep
timeFrame: Assessed on each of the four experimental nights, from overnight electroencephalographic recordings following randomized combinations of drug (nimodipine or placebo) and RF-EMF exposure (5G or sham), with a minimum of 3 days washout between sessions
measure: Aperiodic component of the EEG power spectrum during REM sleep
timeFrame: Assessed on each of the four experimental nights, from overnight electroencephalographic recordings following randomized combinations of drug (nimodipine or placebo) and RF-EMF exposure (5G or sham), with a minimum of 3 days washout between sessions
measure: Aperiodic component of the EEG power spectrum during wakefulness
timeFrame: Assessed on each of the four experimental nights, from pre- and post-sleep wake electroencephalographic recordings
measure: Periodic component of the EEG power spectrum during NREM sleep
timeFrame: Assessed on each of the four experimental nights, from overnight electroencephalographic recordings following randomized combinations of drug (nimodipine or placebo) and RF-EMF exposure (5G or sham), with a minimum of 3 days washout between sessions
measure: Periodic component of the EEG power spectrum during REM sleep
timeFrame: Assessed on each of the four experimental nights, from overnight electroencephalographic recordings following randomized combinations of drug (nimodipine or placebo) and RF-EMF exposure (5G or sham), with a minimum of 3 days washout between sessions.
measure: Periodic component of the EEG power spectrum during wakefulness
timeFrame: Assessed on each of the four experimental nights, from pre- and post-sleep wake electroencephalographic recordings
measure: Sleep efficiency
timeFrame: Assessed on each of the four experimental nights, from overnight electroencephalographic recordings following randomized combinations of drug (nimodipine or placebo) and RF-EMF exposure (5G or sham), with a minimum of 3 days washout between sessions
measure: Sleep latency
timeFrame: Assessed on each of the four experimental nights, from overnight electroencephalographic recordings following randomized combinations of drug (nimodipine or placebo) and RF-EMF exposure (5G or sham), with a minimum of 3 days washout between sessions.
measure: Wakefulness after sleep onset
timeFrame: Assessed on each of the four experimental nights, from overnight electroencephalographic recordings following randomized combinations of drug (nimodipine or placebo) and RF-EMF exposure (5G or sham), with a minimum of 3 days washout between sessions
measure: Time spent in the different sleep stages
timeFrame: Assessed on each of the four experimental nights, from overnight electroencephalographic recordings following randomized combinations of drug (nimodipine or placebo) and RF-EMF exposure (5G or sham), with a minimum of 3 days washout between sessions
measure: Neurocognitive performance as assessed in the sequential finger tapping task (FTT)
timeFrame: Assessed on each of the four experimental nights, pre- and post-sleep
measure: Neurocognitive performance as assessed in the visuospatial 2D Object Location Task (OLT)
timeFrame: Assessed on each of the four experimental nights, pre- and post-sleep
measure: Heart rate variability
timeFrame: Assessed on each of the four experimental nights, from electrocardiographic recordings during pre-sleep exposure and polysomnographic overnight recordings
measure: Pupil size
timeFrame: Assessed on each of the four experimental nights, from pupillometry recordings during pre-sleep exposure.
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University of Zurich, Institute of Pharmacology and Toxicology
Study officials:
References: