Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000186853
Ethics application status
Approved
Date submitted
28/10/2020
Date registered
22/02/2021
Date last updated
22/02/2021
Date data sharing statement initially provided
22/02/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effect of non-invasive neuromodulation of the pineal gland in healthy, adult males
Scientific title
The effect of non-invasive electrical stimulation on the pineal gland sympathetic pathway and sleep metrics in a healthy, male, adult population.
Secondary ID [1] 301939 0
None
Universal Trial Number (UTN)
Trial acronym
SPECTRON
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sleep


 318483 0
Condition category
Condition code
Neurological 316485 316485 0 0
Studies of the normal brain and nervous system
Mental Health 317998 317998 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The sleep hygiene of healthy adult, male participants, between 18-55 years old is appraised for three nights prior to the experimental intervention. Participants’ sleep hygiene will be assessed via both subjective and objective measures. The subjective measures will be recorded via the use of a sleep diary which records subjective reporting of information pertaining to sleep time, wake time, time spent asleep, number of awakenings, length of time spent awake, ease of falling asleep, sleep disturbance, feeling of refreshment following awakening, caffeine and alcohol consumption, heavy meal consumption 2-3 hours prior to sleep, the likelihood of daytime dozing, and mood. Objective measures obtained from the wrist-worn actigraph devices include: sleep time, wake time, sleep duration, sleep onset latency, wake after sleep onset, sleep efficiency, light exposure, and any time the actigraph device was not worn.

If participants’ sleep hygiene is assessed as suitable for the study, they progress to the experimental phase. The experimental phase consists of a researcher-lead stimulation session during the day and a participant-lead stimulation session during the night. Each stimulation frequency is applied for one day time and one night time phase. For the experimental phase during the day, measures of sleepiness, pupil diameter, and blood flow changes are captured using electroencephalography (EEG), eye-tracker glasses, and pulse oximetry, respectively. These measures are used before, during, and after 10 minutes of transcutaneous electrical nerve stimulation (TENS) delivered at the C2 dermatome. Saliva samples are collected before and after stimulation. The experimental phase during the night is conducted in participants’ homes. Here, they self-administer TENS stimulation at the C2 dermatome for 10 minutes. Saliva samples are self-collected before and after stimulation. Participants record the times they sit down in dim light, collect each saliva sample, and begin and end stimulation. Each stimulation frequency is applied for one day time and one night time phase. Participants record the times they sit down in dim light, collect each saliva sample, and begin and end stimulation.

Following stimulation in either the day or the night, participants will record sleep/wake information in a sleep diary and sleep wearing a single-channel EEG and a wrist-worn actigraphy device in order to assess their sleep. Participants cycle through stimulation at: 10 Hz, 80 Hz, or sham stimulation. All stimulation frequencies (including sham) are performed both during the daytime, researcher-lead phase and the night-time participant-lead phase. These phases are conducted on separate days with a one-day washout period in between. The washout period between stimulation frequencies and/or sham stimulation is two-days.
Intervention code [1] 318228 0
Treatment: Devices
Comparator / control treatment
Placement of the electrodes on the same site C2 dermatome stimulation, but only 1 mA current used (10 Hz frequency).
Control group
Active

Outcomes
Primary outcome [1] 324632 0
Effect of electrical stimulation of the C2 dermatome on melatonin levels
Timepoint [1] 324632 0
measured using pre- and post-stimulation saliva sampling and subsequent ELISA (Buhlmann direct saliva melatonin ELISA)
Primary outcome [2] 325534 0
Effect of electrical stimulation of the C2 dermatome on the sleep time measured objectively via wrist-worn actigraphy.
Timepoint [2] 325534 0
This will be continuously measured during sleep for each intervention night. This is a primary objective.
Primary outcome [3] 326594 0
Effect of electrical stimulation of the C2 dermatome on wake time measured objectively via wrist-worn actigraphy.
Timepoint [3] 326594 0
This will be continuously measured during sleep for each intervention night.
Secondary outcome [1] 385281 0
Effect of electrical stimulation of the C2 dermatome on sedation measured using bispectral (BIS) index of EEG recordings
Timepoint [1] 385281 0
Measured continuously for 10-minutes before, 10-minutes during, and 10 minutes following daytime stimulation
Secondary outcome [2] 388327 0
Effect of electrical stimulation of the C2 dermatome on blood flow to the superficial structures of the head and neck measured using pulse oximetry
Timepoint [2] 388327 0
Measured continuously for 10-minutes before, 10-minutes during, and 10 minutes following daytime stimulation
Secondary outcome [3] 388328 0
Effect of electrical stimulation of the C2 dermatome on pupil diameter measured using eye tracker glasses (Tobii Pro eye tracker)
Timepoint [3] 388328 0
Measured continuously for 10-minutes before, 10-minutes during, and 10 minutes following daytime stimulation
Secondary outcome [4] 392036 0
Effect of electrical stimulation of the C2 dermatome on sleep duration.
Timepoint [4] 392036 0
This will be continuously measured during sleep for each intervention night and will be measured objectively via wrist-worn actigraphy. This is a primary objective.
Secondary outcome [5] 392037 0
Effect of electrical stimulation of the C2 dermatome on sleep onset latency.
Timepoint [5] 392037 0
This will be continuously measured during sleep for each intervention night and will be measured objectively via wrist-worn actigraphy. This is a primary objective.
Secondary outcome [6] 392038 0
Effect of electrical stimulation of the C2 dermatome on wake after sleep onset.
Timepoint [6] 392038 0
This will be continuously measured during sleep for each intervention night and will be measured objectively via wrist-worn actigraphy. This is a primary objective.
Secondary outcome [7] 392039 0
Effect of electrical stimulation of the C2 dermatome on sleep efficiency.
Timepoint [7] 392039 0
This will be continuously measured during sleep for each intervention night and will be measured objectively via wrist-worn actigraphy. This is a primary objective.
Secondary outcome [8] 392040 0
Effect of electrical stimulation of the C2 dermatome on ease of falling asleep.
Timepoint [8] 392040 0
This will be measured subjectively via self-reporting using a sleep diary once following waking up after each intervention night.
Secondary outcome [9] 392041 0
Effect of electrical stimulation of the C2 dermatome on the feeling of refreshment upon awakening.
Timepoint [9] 392041 0
This will be measured subjectively via self-reporting using a sleep diary once following waking up after each intervention night.
Secondary outcome [10] 392042 0
Effect of electrical stimulation of the C2 dermatome on mood.
Timepoint [10] 392042 0
This will be measured subjectively via self-reporting using a sleep diary once following waking up after each intervention night.
Secondary outcome [11] 392043 0
Effect of electrical stimulation of the C2 dermatome on the likelihood of daytime dozing.
Timepoint [11] 392043 0
This will be measured subjectively via self-reporting using a sleep diary once following waking up after each intervention night.

Eligibility
Key inclusion criteria
Healthy, (no neurological/cognitive impairments and not on any regular medication) male volunteers between the ages of 18 and 55 years old, with good sleep hygiene and no problems associated with sleep.
Minimum age
18 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Not consume more than 2 alcoholic drinks per day, not regularly use any recreational drugs, no history of serious medical conditions, no vision impairments other than glasses/contact lenses, no allergies, no plans to travel across time zones or undertake shift work in the next month, not work shifts, not excessively consume caffeine (approx. >6 cups of coffee per day).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
As this is a cross-over study, all participants will receive both frequencies and sham stimulation throughout the course of the study, however, the order in which each they receive each frequency/sham stimulation is randomised via Latin square design in order to counterbalance allocation. Each participant was assigned a unique number and the Latin square was randomly generated using a computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Use of William James design through software ‘Compusense’
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Use of paired sample t-test/ Wilcoxon Sign rank test (dependent on normal sample distribution) to observe the changes in melatonin levels (via saliva samples), pupil diameter, and sleepiness before and after the stimulation stage. Use of repeated-measures ANOVA to observe the time differences in sleep metrics before and after stimulation.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
3/09/2020
Date of last participant enrolment
Anticipated
31/03/2021
Actual
Date of last data collection
Anticipated
31/05/2021
Actual
Sample size
Target
20
Accrual to date
8
Final
Recruitment outside Australia
Country [1] 22810 0
New Zealand
State/province [1] 22810 0
Otago

Funding & Sponsors
Funding source category [1] 306356 0
University
Name [1] 306356 0
University of Otago -PBRF fund
Country [1] 306356 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
University of Otago Department of Anatomy, Lindo Ferguson Building
270 Great King St, Dunedin 9016
New Zealand
Country
New Zealand
Secondary sponsor category [1] 307544 0
None
Name [1] 307544 0
Address [1] 307544 0
Country [1] 307544 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306564 0
University of Otago Human Ethics Committee (Health)
Ethics committee address [1] 306564 0
University of Otago Council PO Box 56 Dunedin 9054 New Zealand
Ethics committee country [1] 306564 0
New Zealand
Date submitted for ethics approval [1] 306564 0
03/06/2020
Approval date [1] 306564 0
19/06/2020
Ethics approval number [1] 306564 0
H20/064

Summary
Brief summary
This study investigates whether non-invasive, electrical stimulation delivered at a specific area of the skin associated with a pathway to a part of the brain responsible for producing melatonin can subsequently alter melatonin levels and therefore, influence sleep. Healthy adult, male volunteers between 18-55 years old will be recruited. We employ two different frequencies (10 Hz and 80 Hz) and a sham stimulation as a control measure to investigate our hypothesis. It is hypothesised that these two different frequencies may exert opposite effects.
Trial website
NA
Trial related presentations / publications
NA
Public notes
None

Contacts
Principal investigator
Name 104298 0
A/Prof Yusuf Ozgur Cakmak
Address 104298 0
Department of Anatomy, School of Biomedical Sciences, University of Otago, Lindo Ferguson Building, 270 Great King Street, 9054, Dunedin
Country 104298 0
New Zealand
Phone 104298 0
+64034793040
Fax 104298 0
Email 104298 0
[email protected]
Contact person for public queries
Name 104299 0
A/Prof Yusuf Ozgur Cakmak
Address 104299 0
Department of Anatomy, School of Biomedical Sciences, University of Otago,Lindo Ferguson Building, 270 Great King Street, 9054, Dunedin
Country 104299 0
New Zealand
Phone 104299 0
+64034793040
Fax 104299 0
Email 104299 0
[email protected]
Contact person for scientific queries
Name 104300 0
A/Prof Yusuf Ozgur Cakmak
Address 104300 0
Department of Anatomy, School of Biomedical Sciences, University of Otago,Lindo Ferguson Building, 270 Great King Street, 9054, Dunedin
Country 104300 0
New Zealand
Phone 104300 0
+64034793040
Fax 104300 0
Email 104300 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The study results will be analysed as groups and results will be published as a research paper.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.